Biomolecules

15 pages, 919 KB

Open AccessArticle

Modulating Effect of Carbohydrate Antigen 125 on the Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure

by Enrique Santas, Arancha Martí-Martínez, Elena Revuelta-López, Sandra Villar, Rafael de la Espriella, Patricia Palau, Pau Llàcer, Gema Miñana, Enrique Rodriguez-Borja, Arturo Carratalá, Arantxa Gonzalez, Antoni Bayés-Genís, Juan Sanchis and Julio Núñez

Biomolecules 2025, 15(9), 1260; https://doi.org/10.3390/biom15091260 (registering DOI) - 30 Aug 2025

Abstract

Inflammation and congestion are key pathophysiological processes in heart failure (HF). Our aim was to evaluate the potential modulatory effect of carbohydrate antigen 125 (CA125) on inflammation, assessed by high-sensitivity C-reactive protein (hs-CRP). We analyzed a cohort of 4043 consecutive patients in whom [...] Read more.

Inflammation and congestion are key pathophysiological processes in heart failure (HF). Our aim was to evaluate the potential modulatory effect of carbohydrate antigen 125 (CA125) on inflammation, assessed by high-sensitivity C-reactive protein (hs-CRP). We analyzed a cohort of 4043 consecutive patients in whom hs-CRP and CA125 levels were measured during a hospitalization for acute HF. Multivariate Cox regression models were applied to assess the association between the biomarkers and all-cause mortality and death/HF rehospitalization at 6 months. In multivariable analysis, a significant interaction between hs-CRP and CA125 was observed for both outcomes (p-value for interaction = 0.036 and <0.001, respectively). hs-CRP was significantly associated with an increased risk of death (HR = 1.27; 95% CI 1.16–1.41; p < 0.001) and death/HF rehospitalization (HR = 1.18; 95% CI 1.09–1.28; p < 0.001) if CA125 > 35 U/mL. In contrast, hs-CRP was not predictive of events when CA125 ≤ 35 U/mL. In conclusion, in patients with acute HF, the association between hs-CRP and clinical outcomes was modulated by CA125 levels. hs-CRP was associated with a higher risk of events only in patients with elevated CA125. These findings support a potential modulatory and amplifying role for CA125 in the inflammatory response in HF. Full article

(This article belongs to the Special Issue Biomolecules in Myocarditis and Inflammatory Heart Disease)

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15 pages, 755 KB

Open AccessReview

Non-Pancreatic Digestive Enzymes

by Drucy Borowitz

Biomolecules 2025, 15(9), 1259; https://doi.org/10.3390/biom15091259 (registering DOI) - 30 Aug 2025

Abstract

Although the pancreas is the organ that produces the most critical digestive enzymes, there are other important contributors to the cleavage of food into absorbable units. Pre-pancreatic digestion of carbohydrates occurs through the action of salivary amylase. Pre-pancreatic digestion of fats is mediated [...] Read more.

Although the pancreas is the organ that produces the most critical digestive enzymes, there are other important contributors to the cleavage of food into absorbable units. Pre-pancreatic digestion of carbohydrates occurs through the action of salivary amylase. Pre-pancreatic digestion of fats is mediated by lingual and gastric lipases, and their action may be important as a signal for coordinated digestion. Pepsin, which is present in the stomach, initiates the digestion of dietary proteins into peptides and amplifies distal proteolysis. The major post-pancreatic intestinal carbohydrate-digesting enzymes are sucrase-isomaltase, maltase-glucoamylase and lactase-phlorizin hydrolase. There are no post-pancreatic mucosal enzymes that act on dietary triglycerides; however, the complete digestion of phospholipids depends on several brush border phospholipases. Intestinal processing is an important contributor to digestion of proteins, although mucosal proteases may serve as signaling proteins rather than as primary adjuncts to dietary protein digestion and absorption. This review describes the role of these non-pancreatic digestive enzymes in supporting nutritional health. Full article

(This article belongs to the Special Issue Digestive Enzymes in Health and Disease)

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21 pages, 2229 KB

Open AccessArticle

A Multi-Ingredient Supplement Improves Body Re-Composition, Ovarian Aging Markers, and Reproductive Success in Young and Middle-Aged Female Mice

by Alessandra Chiarot, Mahek Minhas, Nicoletta M. de Maat, Jenny Doan, Mats I. Nilsson, Bart P. Hettinga, Mehrnoosh Faghih, Michael S. Neal, Joshua P. Nederveen and Mark A. Tarnopolsky

Biomolecules 2025, 15(9), 1258; https://doi.org/10.3390/biom15091258 (registering DOI) - 30 Aug 2025

Abstract

Ovarian aging is characterized by mitochondrial dysfunction, oxidative stress, and inflammation. The development of adjunctive treatments that mitigate age-related subfertility is warranted. We examined the benefits of nutraceutical supplementation (FE; Fertility Enhancer) with mitochondrial antioxidants, anti-inflammatory agents, metabolic activators, vitamins and minerals, and [...] Read more.

Ovarian aging is characterized by mitochondrial dysfunction, oxidative stress, and inflammation. The development of adjunctive treatments that mitigate age-related subfertility is warranted. We examined the benefits of nutraceutical supplementation (FE; Fertility Enhancer) with mitochondrial antioxidants, anti-inflammatory agents, metabolic activators, vitamins and minerals, and amino acids on ovarian aging, metabolic activity, and reproductive success in young (Y; 6-month-old) and middle-aged (O; 11-month-old) female C57BL/6J mice. The mice were fed calorie- and macronutrient-matched diets w/wo the FE supplement for three months and harem mated twice. Daily FE supplementation promoted significant body re-composition, including loss of white adipose tissue (gWAT: −36% vs. CON, p < 0.001), gain of skeletal muscle (SkM: +67% vs. CON, p < 0.001), and improved SkM/gWAT ratio (+185% vs. CON, p < 0.001). Metabolic testing showed enhanced fat oxidation (+38%, p < 0.01) and energy expenditure (+7%, p = 0.051) in FE mice. Breeding and immunoblotting data demonstrated improved reproductive success (Y-CON: 44%, Y-FE: 89%, O-CON: 0%, O-FE: 18%) and a modest attenuation of ovarian aging markers in both FE groups. We surmise that a multi-ingredient supplement, such as the Fertility Enhancer, may improve body re-composition, metabolic activity, and markers of ovarian aging, thus enhancing reproductive health and fertility in females. Full article

(This article belongs to the Special Issue Molecular Aspects of Female Infertility)

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18 pages, 1113 KB

Open AccessArticle

In Vitro and In Vivo Comparisons of Activated Charcoal and Biochar as Dietary Treatments for Controlling Boar Taint

by Melissa Parent, Christine Bone, Lee-Anne Huber and E. James Squires

Biomolecules 2025, 15(9), 1257; https://doi.org/10.3390/biom15091257 (registering DOI) - 30 Aug 2025

Abstract

Activated charcoal (AC) is an adsorbent that can prevent the accumulation of boar taint-causing compounds in the fat, but is not an approved dietary additive for livestock animals. Biochar (BC) is a similar feed-approved charcoal adsorbent that may be an alternative dietary additive [...] Read more.

Activated charcoal (AC) is an adsorbent that can prevent the accumulation of boar taint-causing compounds in the fat, but is not an approved dietary additive for livestock animals. Biochar (BC) is a similar feed-approved charcoal adsorbent that may be an alternative dietary additive to control boar taint. This study was conducted to evaluate AC and BC, both in vitro and in vivo, as dietary treatments for boar taint. This was done by first conducting an in vitro binding study to compare binding between AC, BC, and spent filter aid (SFA) for boar taint compounds. Results of the in vitro study showed that both AC and BC had significantly higher B_max for androstenone (AC: 97.2 ± 0.4% and BC: 84.5 ± 0.8%) and skatole (AC: 106.1 ± 0.2%, BC: 113.2 ± 0.7%), compared to SFA with a B_max of 50.5 ± 0.2% for androstenone and 97.1 ± 5.3% for skatole. AC and BC were then tested as feed additives in finisher diets fed to slaughter weight boars. Both adsorbents were successful at preventing boar taint in a subset of animals (83%), while having no effect on plasma levels of estrone sulfate or androstenone, and growth and performance parameters. These findings suggest that BC is a suitable alternative for AC as a dietary additive to prevent boar taint. Full article

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

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29 pages, 15733 KB

Open AccessArticle

Neuromuscular Defects in a Drosophila Model of the Congenital Disorder of Glycosylation SLC35A2-CDG

by Kazuyoshi Itoh, Masaki Kurogochi, Tadashi Kaname, Jun-ichi Furukawa and Shoko Nishihara

Biomolecules 2025, 15(9), 1256; https://doi.org/10.3390/biom15091256 - 29 Aug 2025

Abstract

SLC35A2-CDG is a congenital disorder of glycosylation caused by mutations in the SLC35A2 gene encoding a Golgi-localized UDP-galactose transporter. This transporter plays an essential role in glycan synthesis by transporting UDP-galactose from the cytoplasm into the Golgi lumen. Its dysfunction leads to impaired [...] Read more.

SLC35A2-CDG is a congenital disorder of glycosylation caused by mutations in the SLC35A2 gene encoding a Golgi-localized UDP-galactose transporter. This transporter plays an essential role in glycan synthesis by transporting UDP-galactose from the cytoplasm into the Golgi lumen. Its dysfunction leads to impaired galactose-containing glycans and various neurological symptoms, although the underlying mechanisms remain largely unknown. We identified a novel SLC35A2-CDG patient carrying a pathogenic variant (c.617_620del, p.(Gln206ArgfsTer45)) who exhibited neurological abnormalities including bilateral ventriculomegaly. To investigate the disease mechanism, we established the first Drosophila model of SLC35A2-CDG. Knockout of Ugalt, the fly ortholog of SLC35A2, resulted in embryonic lethality, indicating its essential role. Knockdown of Ugalt reduced mucin-type O-glycans on muscles and neuromuscular junctions (NMJs), without affecting N-glycans. Ugalt knockdown larvae exhibited mislocalized NMJ boutons accompanied by a deficiency in basement membrane components on muscles. This phenotype resembles that of mutants of dC1GalT1 and dGlcAT-P, both involved in mucin-type O-glycosylation. Genetic interaction between Ugalt and dC1GalT1 was confirmed through double knockdown and double heterozygous analyses. Given that Drosophila NMJs are widely used as a model for mammalian central synapses, our findings suggest that Ugalt regulates NMJ architecture via mucin-type O-glycosylation and provide insights into the molecular basis of neurological abnormalities in SLC35A2-CDG. Full article

(This article belongs to the Special Issue Drosophila as a Model System to Study Metabolism)

36 pages, 2992 KB

Open AccessReview

Structural and Functional Studies on Key Epigenetic Regulators in Asthma

by Muhammad Fakhar, Mehreen Gul and Wenjin Li

Biomolecules 2025, 15(9), 1255; https://doi.org/10.3390/biom15091255 - 29 Aug 2025

Abstract

Asthma is a chronic inflammatory airway disease influenced by both genetic and environmental factors. Recent insights have underscored the pivotal role of epigenetic regulation in the pathogenesis and heterogeneity of asthma. This review focuses on key epigenetically important regulators categorized as writers, erasers, [...] Read more.

Asthma is a chronic inflammatory airway disease influenced by both genetic and environmental factors. Recent insights have underscored the pivotal role of epigenetic regulation in the pathogenesis and heterogeneity of asthma. This review focuses on key epigenetically important regulators categorized as writers, erasers, and readers that govern DNA methylation, histone modifications, and RNA modifications. These proteins modulate gene expression without altering the underlying DNA sequence, thereby influencing immune responses, airway remodeling, and disease severity. We highlight the structural and functional dynamics of histone acetyltransferases (e.g., p300/CBP), histone deacetylases (e.g., SIRT family), DNA methyltransferases (DNMT1, DNMT3A), demethylases (TET1), and methyl-CpG-binding proteins (MBD2) in shaping chromatin accessibility and transcriptional activity. Additionally, the m6A RNA modification machinery including METTL3, METTL14, FTO, YTHDF1/2, IGF2BP2, and WTAP is explored for its emerging significance in regulating post-transcriptional gene expression during asthma progression. Structural characterizations of these proteins reveal conserved catalytic domains and interaction motifs, mirroring their respective families such as SIRTs, p300/CBP, DNMT1/3A, and YTHDF1/2 critical to their epigenetic functions, offering mechanistic insight into their roles in airway inflammation and immune modulation. By elucidating these pathways, this review provides a framework for the development of epigenetic biomarkers and targeted therapies. Future directions emphasize phenotype-specific epigenomic profiling and structure-guided drug design to enable precision medicine approaches in asthma management. Full article

(This article belongs to the Section Molecular Genetics)

25 pages, 5121 KB

Open AccessArticle

Biomarker Signatures in Time-Course Progression of Neuropathic Pain at Spinal Cord Level Based on Bioinformatics and Machine Learning Analysis

by Kexin Li, Ruoxi Wang, He Zhu, Bei Wen, Li Xu and Yuguang Huang

Biomolecules 2025, 15(9), 1254; https://doi.org/10.3390/biom15091254 - 29 Aug 2025

Abstract

Neuropathic pain (NP) is a debilitating chronic pain condition with complex molecular mechanisms and inadequate therapeutic solutions. This study aims to identify temporal transcriptomic changes in NP using multiple bioinformatics and machine learning algorithms. A total of 10 mouse samples (5 per group) [...] Read more.

Neuropathic pain (NP) is a debilitating chronic pain condition with complex molecular mechanisms and inadequate therapeutic solutions. This study aims to identify temporal transcriptomic changes in NP using multiple bioinformatics and machine learning algorithms. A total of 10 mouse samples (5 per group) were harvested at each time point (day three, day seven, and day fourteen), following spared nerve injury and a sham operation. Differentially expressed gene (DEG) analysis and an intersection among the three time-point groups revealed 54 common DEGs. The GO and KEGG analyses mainly showed enrichment in terms of immune response, cell migration, and signal transduction functions. In addition, the interaction of the LASSO, RF, and SVM-RFE machine learning models on 54 DEGs resulted in Ngfr and Ankrd1. The cyan module in WGCNA was selected for a time-dependent upward trend in gene expression. Then, 172 genes with time-series signatures were integrated with 54 DEGs, resulting in 11 shared DEGs. Quantitative RT-PCR validated the temporal expressions of the above genes, most of which have not been reported yet. Additionally, immune infiltration analysis revealed significant positive correlations between monocyte abundance and the identified genes. The TF-mRNA-miRNA network and drug-target network revealed potential therapeutic drugs and posttranscriptional regulatory mechanisms. In conclusion, this study explores genes with time-series signatures as biomarkers in the development and maintenance of NP, potentially revealing novel targets for analgesics. Full article

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

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15 pages, 1535 KB

Open AccessArticle

Antibiofilm Inhibitor Ferulic Acid as an Antibacterial Synergist Against Escherichia coli

by Zhijin Zhang, Jing Xu, Xiaojuan Wei, Rongbin Hu, Zhen Zhu, Zixuan Shang, Weiwei Wang, Bing Li, Yubin Bai and Jiyu Zhang

Biomolecules 2025, 15(9), 1253; https://doi.org/10.3390/biom15091253 - 29 Aug 2025

Abstract

Escherichia coli (E. coli) is a severe foodborne pathogen, and the formation of its biofilm can enhance bacterial virulence and reduce antibiotic sensitivity, posing a significant threat to human and animal health. Ferulic Acid (FA) is a natural active product that [...] Read more.

Escherichia coli (E. coli) is a severe foodborne pathogen, and the formation of its biofilm can enhance bacterial virulence and reduce antibiotic sensitivity, posing a significant threat to human and animal health. Ferulic Acid (FA) is a natural active product that has been proven to possess various biological activities, including anti-inflammatory, antioxidant, and antitumor properties. This study evaluated the inhibitory effect of FA on the biofilm formation of E. coli through crystal violet (CV) staining and scanning electron microscopy (SEM) and investigated the synergistic effect of FA with antibiotics, using the alamar blue (AB) assay. In addition, the regulatory effect of FA on the transcription of biofilm-related genes was analyzed using qRT-PCR technology. The results showed that FA could significantly inhibit biofilm formation, reduce the production of extracellular polymeric substances (EPS), and weaken bacterial motility, without affecting bacterial growth and metabolic activity. qRT-PCR analysis revealed that FA significantly downregulated the expression of curli-related gene csgD, flagella-related genes (flhC, flhD, and motA), and type I fimbriae gene fimA, while upregulating the transcription of c-di-GMP-related genes (pdeR, pdeA, and dosP). It is noteworthy that FA exhibits significant synergistic antibacterial effects when combined with clinically commonly used antibiotics, including sodium fosfomycin, ceftriaxone, gentamicin, and tetracycline, with the most prominent synergistic effect observed in the combination of FA and sodium fosfomycin. These results confirm that FA possesses notable anti-biofilm activity and novel synergistic antibacterial properties, providing a potential therapeutic strategy for treating E. coli infections. Full article

(This article belongs to the Special Issue Novel Mechanisms of Bacterial Antibiotic Resistance)

32 pages, 1814 KB

Open AccessReview

Mitochondrial Aging in the CNS: Unravelling Implications for Neurological Health and Disease

by Davide Steffan, Camilla Pezzini, Martina Esposito and Anais Franco-Romero

Biomolecules 2025, 15(9), 1252; https://doi.org/10.3390/biom15091252 - 29 Aug 2025

Abstract

Mitochondrial aging plays a central role in the functional decline of the central nervous system (CNS), with profound consequences for neurological health. As the brain is one of the most energy-demanding organs, neurons are particularly susceptible to mitochondrial dysfunction that arises with aging. [...] Read more.

Mitochondrial aging plays a central role in the functional decline of the central nervous system (CNS), with profound consequences for neurological health. As the brain is one of the most energy-demanding organs, neurons are particularly susceptible to mitochondrial dysfunction that arises with aging. Key features of mitochondrial aging include impaired mitochondrial dynamics, reduced mitophagy, increased production of reactive oxygen species (ROS), and accumulation of mitochondrial DNA (mtDNA) mutations. These alterations dramatically compromise neuronal bioenergetics, disrupt synaptic integrity, and promote oxidative stress and neuroinflammation, paving the path for the development of neurodegenerative diseases. This review also examines the complex mechanisms driving mitochondrial aging in the central nervous system (CNS), including the disruption of mitochondrial-organelle communication, and explores how mitochondrial dysfunction contributes to neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. By synthesizing current evidence and identifying key knowledge gaps, we emphasize the urgent need for targeted strategies to restore mitochondrial function, maintain cognitive health, and delay or prevent age-related neurodegeneration. Full article

(This article belongs to the Special Issue Mitochondria and Central Nervous System Disorders: 3rd Edition)

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16 pages, 3705 KB

Open AccessArticle

Construction of Yeast One-Hybrid Library of Dendrobium huoshanense and Screening of Potential Transcription Factors Regulating DhPMM Gene Expression

by Jing Wu, Shuting Wang, Shihai Xing and Daiyin Peng

Biomolecules 2025, 15(9), 1251; https://doi.org/10.3390/biom15091251 - 29 Aug 2025

Abstract

Dendrobium huoshanense, an endangered orchid species, is renowned for its polysaccharides with vast pharmacological significance in stems. Phosphomannomutase (PMM) critically regulates polysaccharide accumulation. Transcriptional regulation of DhPMM remains poorly characterized. This study employed a yeast one-hybrid (Y1H) system to identify upstream regulators [...] Read more.

Dendrobium huoshanense, an endangered orchid species, is renowned for its polysaccharides with vast pharmacological significance in stems. Phosphomannomutase (PMM) critically regulates polysaccharide accumulation. Transcriptional regulation of DhPMM remains poorly characterized. This study employed a yeast one-hybrid (Y1H) system to identify upstream regulators of DhPMM. The 2.15 kb DhPMM promoter was cloned, revealing multiple stress- and hormone-responsive cis-elements (e.g., ABRE, MYC, ERF). A high-complexity Y1H library (3.60 × 10⁹ CFU) was constructed with insert sizes averaging 1–2 kb. Screening using aureobasidin A (AbA)-resistant Y1HGold [pAbAi-DhPMM] identified 11 candidate clones, including four transcription factor families (DOF, NAC, ERF, BES1). Interactions were rigorously confirmed by pairwise Y1H showing AbA-resistant growth and dual-luciferase assays demonstrating DhPMM activation. This represents the first functional cDNA library resource for D. huoshanense and identification of TFs interacting with DhPMM. The discovery of TFs belonging to DOF, NAC, ERF, and BES1 families as DhPMM regulators elucidated the transcriptional network underlying polysaccharide biosynthesis. This establishes a transcriptional framework for engineering polysaccharide biosynthesis in D. huoshanense. Full article

(This article belongs to the Section Biological Factors)

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21 pages, 2220 KB

Open AccessReview

Ashes to Rashes: An Exploration of the Intersection Between Smoking and Cutaneous Lupus Erythematosus

by Rafael O. Homer, Ahmed Eldaboush, Darae Kang, Nada S. Ahmed, Touraj Khosravi-Hafshejani, Ming-Lin Liu and Victoria P. Werth

Biomolecules 2025, 15(9), 1250; https://doi.org/10.3390/biom15091250 - 29 Aug 2025

Abstract

Cutaneous lupus erythematosus is an autoimmune skin disorder with a known association with cigarette smoking. Smokers with cutaneous lupus have a worse disease course and may be refractory to treatments. Despite many studies documenting this association, minimal work exists examining the molecular drivers [...] Read more.

Cutaneous lupus erythematosus is an autoimmune skin disorder with a known association with cigarette smoking. Smokers with cutaneous lupus have a worse disease course and may be refractory to treatments. Despite many studies documenting this association, minimal work exists examining the molecular drivers of these clinical differences. This review delves into how cigarette smoke may influence key immunopathogenic pathways in cutaneous lupus, including oxidative stress, interferon signaling, inflammatory cell recruitment, extracellular vesicles, and immune regulation. Additionally, factors such as epigenetics and heat injury are considered as well. Here, we integrate the existing and emerging literature on the pathophysiology of cutaneous lupus with known effects of cigarette smoke on the skin and immune system and propose hypotheses that may explain clinical differences in smokers. Understanding the molecular underpinnings of these differences may yield a clearer picture of the disease and more effective treatment strategies. Full article

(This article belongs to the Section Biological Factors)

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21 pages, 1191 KB

Open AccessReview

Glycerol Kinase 2 as a Metabolic Sentinel for Human Sperm Motility and Male Fertility

by João S. Oliveira, Rúben J. Moreira, Ana D. Martins, Marco G. Alves and Pedro F. Oliveira

Biomolecules 2025, 15(9), 1249; https://doi.org/10.3390/biom15091249 - 29 Aug 2025

Abstract

Male infertility affects 8–12% of couples worldwide and is solely responsible in up to 30% of cases. Assisted Reproductive Technologies (ARTs) provide potential solutions, particularly in conditions where spermatozoa display structural abnormalities or impaired motility, such as asthenozoospermia. Sperm metabolism demonstrates remarkable flexibility, [...] Read more.

Male infertility affects 8–12% of couples worldwide and is solely responsible in up to 30% of cases. Assisted Reproductive Technologies (ARTs) provide potential solutions, particularly in conditions where spermatozoa display structural abnormalities or impaired motility, such as asthenozoospermia. Sperm metabolism demonstrates remarkable flexibility, shifting between glycolysis and oxidative phosphorylation to produce ATP required for motility. Glycerol kinase 2 (GK2) phosphorylates glycerol in the sperm midpiece, generating glycerol-3-phosphate, a key intermediate in glycolysis, lipid metabolism, and oxidative phosphorylation. The localization of GK2 suggests not only a regulatory role in sperm metabolism but also a possible association with VDAC proteins, contributing to ADP-ATP exchange between the cytosol and mitochondria. Elucidating the role of GK2 in spermatozoa is of particular relevance, as this enzyme not only contributes to key metabolic pathways but may also interact with VDAC proteins, influencing mitochondrial function and energy exchange. Such interactions could play a pivotal role in regulating sperm motility. A deeper understanding of these mechanisms could position GK2 as a valuable biomarker: in scenarios where GK2–VDAC interactions are confirmed, it may guide optimized sperm selection methods in ARTs, whereas the absence or impairment of such interactions could serve as a diagnostic indicator in asthenozoospermic men. Full article

(This article belongs to the Special Issue Advances in Metabolomics in Health and Disease)

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21 pages, 4257 KB

Open AccessArticle

Repetitive DNAs and Karyotype Evolution in Phyllostomid Bats (Chiroptera: Phyllostomidae)

by Geize Aparecida Deon, Tariq Ezaz, José Henrique Forte Stornioli, Rodrigo Zeni dos Santos, Anderson José Baia Gomes, Príncia Grejo Setti, Edivaldo Herculano Correa de Oliveira, Fábio Porto-Foresti, Ricardo Utsunomia, Thomas Liehr and Marcelo de Bello Cioffi

Biomolecules 2025, 15(9), 1248; https://doi.org/10.3390/biom15091248 - 29 Aug 2025

Abstract

Bats are great models for studying repetitive DNAs due to their compact genomes and extensive chromosomal rearrangements. Here, we investigated the repetitive DNA content of two phyllostomid bat species, Artibeus lituratus (2nn = 30♀/31♂) and Carollia perspicillata (2n = 20♀/21♂), both [...] Read more.

Bats are great models for studying repetitive DNAs due to their compact genomes and extensive chromosomal rearrangements. Here, we investigated the repetitive DNA content of two phyllostomid bat species, Artibeus lituratus (2nn = 30♀/31♂) and Carollia perspicillata (2n = 20♀/21♂), both harboring a multiple XY₁Y₂ sex chromosome system. Satellite DNA (satDNA) libraries were isolated and characterized, revealing four and ten satDNA families in A. lituratus and C. perspicillata, respectively. These sequences, along with selected microsatellites, were in situ mapped onto chromosomes in both species and phylogenetically related taxa. SatDNAs showed strong accumulation in centromeric and subtelomeric regions, especially pericentromeric areas. Cross-species mapping with C. perspicillata-derived probes indicated terminal localization patterns in other bat species, suggesting conserved distribution. Microsatellites co-localized with 45S rDNA clusters on the neo-sex chromosomes. Additionally, genomic hybridization revealed a male-specific signal on the Y₁ chromosome, pointing to potential sex-linked repetitive regions. These findings confirm that bat genomes display relatively low amounts of repetitive DNA compared to other mammals and underscore the role of these elements in genome organization and sex chromosome evolution in phyllostomid bats. Full article

(This article belongs to the Section Molecular Genetics)

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18 pages, 2449 KB

Open AccessArticle

Consequences of Adhesion Molecule Close Homolog of L1 Deficiency for Neurons and Glial Cells in the Mouse Spinal Cord After Injury

by Igor Jakovcevski, Ayse Acar, Benjamin Schwindenhammer, Mohammad I.K. Hamad, Gebhard Reiss, Eckart Förster and Melitta Schachner

Biomolecules 2025, 15(9), 1247; https://doi.org/10.3390/biom15091247 - 28 Aug 2025

Abstract

After spinal cord injury, pathological changes predominantly proceed caudal to the site of injury. To what extent these changes contribute to abnormalities during regeneration is poorly understood. Here, we addressed this question with a low-thoracic compression injury mouse model. The total numbers of [...] Read more.

After spinal cord injury, pathological changes predominantly proceed caudal to the site of injury. To what extent these changes contribute to abnormalities during regeneration is poorly understood. Here, we addressed this question with a low-thoracic compression injury mouse model. The total numbers of immunohistochemically stained neuronal and glial cell types in the lumbar spinal cord were stereologically determined 6 weeks after injury. We also investigated injured mice deficient in close homolog of L1 (CHL1), which had been reported to recover better after injury than their wild-type littermates. We here report that there were no differences between genotypes in uninjured animals. In both injured CHL1-deficient and wild-type littermates, gray and white matter volumes were decreased as compared with uninjured mice. Numbers of motoneurons and parvalbumin-expressing interneurons were also reduced in both genotypes. Numbers of interneurons in injured mutant mice were lower than in wild-type littermates. Whereas injury did not affect numbers of astrocytes and oligodendrocytes in the gray matter, numbers of microglia/macrophages were increased. In the mutant white matter, numbers of oligodendrocytes were reduced, with no changes in numbers of astrocytes and microglia. A loss of motoneurons and interneurons was observed in both genotypes, but loss of interneurons was more prominent in the absence of CHL1. We propose that, after injury, CHL1 deficiency causes deficits in structural outcome not seen after injury of wild-type mice. Full article

(This article belongs to the Collection Feature Papers in Section 'Molecular Medicine')

17 pages, 2733 KB

Open AccessArticle

A Novel Clonorchis sinensis Mitogenome: Elucidating Multiregional Strain Phylogeny and Revising the Digenean Mitochondrial Genome Tree

by Yuxuan Liu, Kaisong Hu, Yanan Zhang, Zhili Chen, Haoyu Zheng, Yuexi Teng, Fang Wang and Jingtong Zheng

Biomolecules 2025, 15(9), 1246; https://doi.org/10.3390/biom15091246 - 28 Aug 2025

Abstract

Clonorchis sinensis, a parasitic liver fluke, is the primary aetiological agent of clonorchiasis, a disease predominantly characterized by liver-related clinical manifestations. Currently, research on the complete mitochondrial (mt) genome of local C. sinensis populations remains inadequate. Thus, in this study, we sequenced [...] Read more.

Clonorchis sinensis, a parasitic liver fluke, is the primary aetiological agent of clonorchiasis, a disease predominantly characterized by liver-related clinical manifestations. Currently, research on the complete mitochondrial (mt) genome of local C. sinensis populations remains inadequate. Thus, in this study, we sequenced and annotated the mt genome of fish-borne C. sinensis (Cs-c2) from Changchun, Jilin Province, China, a strain not previously described. This mt genome is 14,136 bp in length and harbours 12 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and a single control region (CR). We constructed a maximum likelihood (ML) phylogenetic tree using concatenated ND5, ND6, and ND1 from protein-coding genes (PCGs) of the C. sinensis mitochondrial genome (mt genome). This tree more clearly differentiated C. sinensis strains from three geographical regions (China, Russia, and South Korea) and distinguished Opisthorchiidae from two closely related families (Fasciolidae and Dicrocoeliidae). Additionally, we constructed an ML phylogenetic tree using concatenated ND4, ND5, ND1, ND2, and COX1 from the PCGs of digenean (Digenea) mt genomes. This approach—utilizing multiple high-resolution PCGs with evolutionary rates distinct from those of the mt genome—yielded robust clustering for multiple suborders and 13 families within Digenea and provided new molecular evidence for intergeneric relationships within the suborder Plagiorchiata of Digenea. These findings serve as important references for future research on the differentiation of closely related geographical strains of digeneans, as well as for studies on molecular taxonomy and population genetics. Full article

(This article belongs to the Section Molecular Genetics)

15 pages, 6628 KB

Open AccessArticle

Targeting Integrin α2 to Overcome Imatinib Resistance in Chronic Myeloid Leukemia Cells

by Yalda Hekmatshoar, Tulin Ozkan, Arzu Zeynep Karabay, Sureyya Bozkurt, Aynur Karadag Gurel, Ozlem Kurnaz Gomleksiz, Tunc Fisgin and Asuman Sunguroglu

Biomolecules 2025, 15(9), 1245; https://doi.org/10.3390/biom15091245 - 28 Aug 2025

Abstract

Chronic myeloid leukemia (CML) is a blood disorder caused by a genetic alteration that creates the BCR-ABL fusion gene, leading to continuous activation of cell growth signals and uncontrolled proliferation of the blood cells. Imatinib (IMA) resistance remains a major obstacle in CML [...] Read more.

Chronic myeloid leukemia (CML) is a blood disorder caused by a genetic alteration that creates the BCR-ABL fusion gene, leading to continuous activation of cell growth signals and uncontrolled proliferation of the blood cells. Imatinib (IMA) resistance remains a major obstacle in CML treatment. Integrins, particularly integrin α2 (ITGA2), have been associated with cancer progression and drug resistance. In the current study, we investigated the role of ITGA2 in IMA resistance using IMA-sensitive K562 (K562S) and IMA-resistant K562 (K562R) cells. Our findings showed that ITGA2 is overexpressed in K562R cells and ITGA2 inhibitor E7820 (2.5 µM) treatment significantly decreased cell viability and induced apoptosis in both sensitive and resistant cells. Combination treatment with E7820 and imatinib enhanced pro-apoptotic gene expression (BAX, BIM) and decreased anti-apoptotic BCL2 levels in imatinib-resistant K562R cells. Flow cytometry confirmed ITGA2 inhibition at the protein level, and rhodamine assays revealed reduced MDR1 activity in treated cells. These results demonstrate that targeting ITGA2 may overcome imatinib resistance and offer a novel therapeutic strategy for CML. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Targets in Leukaemia)

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25 pages, 1464 KB

Open AccessReview

Ca²⁺ Signaling in Striated Muscle Cells During Intracellular Acidosis

by Florentina Pluteanu, Boris Musset and Andreas Rinne

Biomolecules 2025, 15(9), 1244; https://doi.org/10.3390/biom15091244 - 28 Aug 2025

Abstract

The cytosolic pH (pH_i) of mammalian cells is tightly maintained at values ~7.2. Cytoplasmic acidosis (pH_i < 6.8) occurs when the intracellular proton concentration ([H⁺]_i) exceeds the buffering capacity of the cytosol and transport processes to [...] Read more.

The cytosolic pH (pH_i) of mammalian cells is tightly maintained at values ~7.2. Cytoplasmic acidosis (pH_i < 6.8) occurs when the intracellular proton concentration ([H⁺]_i) exceeds the buffering capacity of the cytosol and transport processes to extrude protons are exhausted. During intracellular acidosis, the contractility of cardiac and skeletal muscle cells is strongly reduced, often at sufficient Ca²⁺ levels. A contraction of striated muscle is achieved when the intracellular calcium (Ca²⁺) concentration rises above resting levels. The amplitude and kinetics of Ca²⁺ signals are controlled by Ca²⁺ handling proteins and force is generated if Ca²⁺ ions interact with contractile filaments of the sarcomere. Some aspects of this phenomenon, such as the biochemical origin of excessive protons in working muscle cells and molecular interactions of protons with Ca²⁺ handling proteins or contractile filaments, are not yet fully understood. This review summarizes our current understanding of how striated muscle cells handle Ca²⁺ and H⁺ and how a rise in [H⁺]_i may interfere with Ca²⁺ signaling in the working skeletal muscle (fatigue) or during ischemic events in cardiac muscle. Finally, we briefly address experimental strategies to measure Ca²⁺ signaling at different pH values with fluorescent probes and highlight their limitations. Full article

(This article belongs to the Special Issue The Role of Calcium Signaling in Cardiac and Skeletal Muscle)

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27 pages, 4448 KB

Open AccessArticle

CD45 and Basigin (CD147) Are Functional Ligands for Galectin-8 on Human Leukocytes

by Jean-Philippe F. Gourdine, Porfirio Nava, Alexander J. Noll, Duc M. Duong, Nicholas T. Seyfried and Richard D. Cummings

Biomolecules 2025, 15(9), 1243; https://doi.org/10.3390/biom15091243 - 27 Aug 2025

Abstract

The interactions of leukocyte glycoproteins with adhesion and signaling molecules through glycan recognition are not well understood. We previously demonstrated that galectin-8, a tandem-repeat lectin with N- and C-terminal carbohydrate binding domains which is highly expressed in endothelial and epithelial cells, can bind [...] Read more.

The interactions of leukocyte glycoproteins with adhesion and signaling molecules through glycan recognition are not well understood. We previously demonstrated that galectin-8, a tandem-repeat lectin with N- and C-terminal carbohydrate binding domains which is highly expressed in endothelial and epithelial cells, can bind to activated neutrophils to induce surface exposure of phosphatidylserine (PS) without DNA fragmentation or apoptosis, in a process termed preaparesis. However, the receptors for Gal-8 on leukocytes have not been identified. Here we report our results using both proteomics and affinity chromatography with both full-length Gal-8 and the separate Gal-8 C-terminal and N-terminal domains to identify glycoprotein ligands in HL-60 cells for Gal-8. Two of the major ligands for Gal-8 are CD45RA and CD45RC (Protein Tyrosine Phosphatase, PTP) and basigin (CD147). Both CD45 and basigin are integral membrane glycoproteins that carry poly-N-acetyllactosamine modifications on N- and/or O-glycans, required for Gal-8 binding. Inhibition of the phosphatase activity of CD45 reduced Gal-8-induced PS exposure, indicating a possible role of CD45 in Gal-8 signaling of preaparesis in human leukocytes. These results demonstrate unique glycoprotein recognition by Gal-8 involved in cell recognition and signaling. Full article

(This article belongs to the Section Cellular Biochemistry)

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23 pages, 4058 KB

Open AccessArticle

Inhibition of Astrocyte Reactivity by Mdivi-1 After Status Epilepticus in Rats Exacerbates Microglia-Mediated Neuroinflammation and Impairs Limbic–Cortical Glucose Metabolism

by Francisca Gómez-Oliver, Rubén Fernández de la Rosa, Mirjam Brackhan, Pablo Bascuñana, Miguel Ángel Pozo and Luis García-García

Biomolecules 2025, 15(9), 1242; https://doi.org/10.3390/biom15091242 - 27 Aug 2025

Abstract

The lithium–pilocarpine rat model of status epilepticus (SE) is a well-established paradigm for studying epileptogenesis. Astrocyte reactivity has been implicated in modulating seizure susceptibility and neuroinflammation, yet its functional role in early epileptogenesis remains unclear. Herein, we evaluated the effects of Mdivi-1, a [...] Read more.

The lithium–pilocarpine rat model of status epilepticus (SE) is a well-established paradigm for studying epileptogenesis. Astrocyte reactivity has been implicated in modulating seizure susceptibility and neuroinflammation, yet its functional role in early epileptogenesis remains unclear. Herein, we evaluated the effects of Mdivi-1, a pharmacological inhibitor of mitochondrial fission protein Drp1, for its ability to modulate astrocytic mitochondrial dynamics and for its reported preventive neuroprotective properties. Mdivi-1 was administered shortly after SE onset, and we assessed brain glucose metabolism using [¹⁸F]FDG PET, alongside histological markers of neurodegeneration, astrocyte reactivity, and microglial activation, at 3 days post-SE. As expected, SE induced widespread brain hypometabolism measured by a VOI analysis, hippocampal neurodegeneration, and glial activation. Post-SE Mdivi-1 administration reduced hippocampal astrogliosis but neither conferred neuroprotection nor rescued glucose metabolism. On the contrary, Mdivi-1 exacerbated limbic–cortical hypometabolism when evaluated by SPM and normalized to whole brain tracer uptake and microglia-mediated neuroinflammation. These findings challenge the assumption that early astrocyte inhibition confers neuroprotection. Furthermore, early suppression of astrocyte reactivity after the damage has occurred may shift the neuroinflammatory response toward maladaptive microglial activation. Thus, while Mdivi-1 holds promise as a preventive neuroprotective agent, its use post-SE may have unintended adverse effects on the brain’s response to SE. Full article

(This article belongs to the Special Issue Biomolecular Approaches and Drugs for Neurodegeneration—2nd Edition)

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