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Search Results (11,646)

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Keywords = A35R protein

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18 pages, 5419 KiB  
Article
Molecular Surveillance and Whole Genomic Characterization of Bovine Rotavirus A G6P[1] Reveals Interspecies Reassortment with Human and Feline Strains in China
by Ahmed H. Ghonaim, Mingkai Lei, Yang Zeng, Qian Xu, Bo Hong, Dongfan Li, Zhengxin Yang, Jiaru Zhou, Changcheng Liu, Qigai He, Yufei Zhang and Wentao Li
Vet. Sci. 2025, 12(8), 742; https://doi.org/10.3390/vetsci12080742 (registering DOI) - 7 Aug 2025
Abstract
Group A rotavirus (RVA) is a leading causative agent of diarrhea in both young animals and humans. In China, multiple genotypes are commonly found within the bovine population. In this study, we investigated 1917 fecal samples from calves with diarrhea between 2022 and [...] Read more.
Group A rotavirus (RVA) is a leading causative agent of diarrhea in both young animals and humans. In China, multiple genotypes are commonly found within the bovine population. In this study, we investigated 1917 fecal samples from calves with diarrhea between 2022 and 2025, with 695 testing positive for RVA, yielding an overall detection rate of 36.25%. The highest positivity rate was observed in Hohhot (38.98%), and annual detection rates ranged from 26.75% in 2022 to 42.22% in 2025. A bovine rotavirus (BRV) strain, designated 0205HG, was successfully isolated from a fecal sample of a newborn calf. Its presence was confirmed through cytopathic effects (CPEs), the indirect immunofluorescence assay (IFA), electron microscopy (EM), and high-throughput sequencing. Genomic characterization identified the strain as having the G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3 genotype constellation. The structural proteins VP2 and VP7, along with nonstructural genes NSP1–NSP4, shared high sequence identity with Chinese bovine strains, whereas VP1, VP4, and NSP5 clustered more closely with human rotaviruses, and VP3 was related to feline strains. These findings highlight the genetic diversity and interspecies reassortment of BRVs in China, underlining the importance of continued surveillance and evolutionary analysis. Full article
(This article belongs to the Special Issue Viral Infections in Wild and Domestic Animals)
14 pages, 456 KiB  
Article
The Role of Anisakis sp. in α-Gal Sensitization: Implications for Parasitic-Induced Meat Allergy
by Marta Rodero, Sara Romero, Ángela Valcárcel, Juan González-Fernández, A. Sonia Olmeda, Félix Valcárcel, Alvaro Daschner and Carmen Cuéllar
Pathogens 2025, 14(8), 789; https://doi.org/10.3390/pathogens14080789 (registering DOI) - 7 Aug 2025
Abstract
Background/Objectives: This study investigates the potential of Anisakis sp. as a novel source of α-Gal (Galα1-3Galβ1-4GlcNAc-R) epitopes capable of inducing allergic sensitization in humans. While α-Gal is classically associated with delayed IgE-mediated hypersensitivity following tick bites, emerging evidence suggests that parasitic helminths such [...] Read more.
Background/Objectives: This study investigates the potential of Anisakis sp. as a novel source of α-Gal (Galα1-3Galβ1-4GlcNAc-R) epitopes capable of inducing allergic sensitization in humans. While α-Gal is classically associated with delayed IgE-mediated hypersensitivity following tick bites, emerging evidence suggests that parasitic helminths such as Anisakis sp. may also express α-Gal-containing glycoconjugates, offering an alternative sensitization pathway. Methods: Protein extracts from Anisakis sp. third-stage larvae and mammalian tissues (beef, pork) were analyzed by SDS-PAGE and Western blot using a monoclonal anti-α-Gal antibody (clone M86), and α-Gal epitopes were detected by ELISA. Sera from urticaria patients, stratified by Anisakis sp. sensitization status, were evaluated for anti-α-Gal IgG, IgE, and IgG4 antibodies. Inhibition assays assessed cross-reactivity. Results: Results confirmed the presence of α-Gal epitopes on Anisakis sp. proteins, with prominent bands at ~250 kDa and 65 kDa. Urticaria patients sensitized to Anisakis sp. exhibited significantly elevated anti-α-Gal antibody levels compared to controls. Inhibition ELISA demonstrated substantial reduction in antibody binding with Anisakis sp. extracts, indicating shared antigenic determinants with mammalian α-Gal. Conclusions: These findings establish Anisakis sp. as a source of α-Gal-containing glycoproteins capable of eliciting specific antibody responses in humans, highlighting a potential parasitic route for α-Gal sensitization. Full article
(This article belongs to the Special Issue Molecular Aspects of Host-Parasite Interactions)
21 pages, 7477 KiB  
Article
Bidirectional Hypoxic Extracellular Vesicle Signaling Between Müller Glia and Retinal Pigment Epithelium Regulates Retinal Metabolism and Barrier Function
by Alaa M. Mansour, Mohamed S. Gad, Samar Habib and Khaled Elmasry
Biology 2025, 14(8), 1014; https://doi.org/10.3390/biology14081014 - 7 Aug 2025
Abstract
The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia [...] Read more.
The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood–retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles’ (EVs’) signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood–retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies. Full article
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20 pages, 2823 KiB  
Article
Pro-Reparative Effects of KvLQT1 Potassium Channel Activation in a Mouse Model of Acute Lung Injury Induced by Bleomycin
by Tom Voisin, Alban Girault, Mélissa Aubin Vega, Émilie Meunier, Jasmine Chebli, Anik Privé, Damien Adam and Emmanuelle Brochiero
Int. J. Mol. Sci. 2025, 26(15), 7632; https://doi.org/10.3390/ijms26157632 - 7 Aug 2025
Abstract
Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich [...] Read more.
Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K+) channels—particularly KvLQT1, expressed in alveolar cells—in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K+ channel may be a potential target for the resolution of the acute phase of ARDS. Full article
(This article belongs to the Special Issue Lung Diseases Molecular Pathogenesis and Therapy)
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17 pages, 10110 KiB  
Article
An Integrated Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation Study to Investigate the Potential Mechanism of Isoliquiritigenin in the Treatment of Ischemic Stroke
by Hang Yuan, Yuting Hou, Yuan Jiao, Xin Lu and Liang Liu
Curr. Issues Mol. Biol. 2025, 47(8), 627; https://doi.org/10.3390/cimb47080627 - 6 Aug 2025
Abstract
Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used [...] Read more.
Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used to predict potential targets related to the anti-IS effect of ISL. The binding ability of ISL to potential core targets was further analyzed by molecular docking and molecular dynamics (MD) simulations. By establishing an oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cell model, the anti-IS mechanisms of ISL were investigated via RT-qPCR and Western Blot (WB). As a result, network pharmacology analysis revealed that APP, ESR1, MAO-A, PTGS2, and EGFR may be potential core targets of ISL for anti-IS treatment. Molecular docking and molecular dynamics simulation results revealed that ISL can stably bind to the five potential core targets and form stable complex systems with them. The results of the cell experiments revealed a significant anti-IS effect of ISL. Additionally, mRNA and protein expression levels of APP, MAO-A and PTGS2 or ESR1 in the ISL treatment group were significantly lower or higher than those in the OGD/R group In conclusion, ISL may improve IS by regulating the protein expression levels of APP, ESR1, MAO-A, and PTGS2. Full article
(This article belongs to the Special Issue Cerebrovascular Diseases: From Pathogenesis to Treatment)
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21 pages, 3840 KiB  
Article
Identification of CaVβ1 Isoforms Required for Neuromuscular Junction Formation and Maintenance
by Amélie Vergnol, Aly Bourguiba, Stephanie Bauché, Massiré Traoré, Maxime Gelin, Christel Gentil, Sonia Pezet, Lucile Saillard, Pierre Meunier, Mégane Lemaitre, Julianne Perronnet, Frederic Tores, Candice Gautier, Zoheir Guesmia, Eric Allemand, Eric Batsché, France Pietri-Rouxel and Sestina Falcone
Cells 2025, 14(15), 1210; https://doi.org/10.3390/cells14151210 - 6 Aug 2025
Abstract
Voltage-gated Ca2+ channels (VGCCs) are regulated by four CaVβ subunits (CaVβ1–CaVβ4), each showing specific expression patterns in excitable cells. While primarily known for regulating VGCC function, CaVβ proteins also have channel-independent roles, including gene expression modulation. Among these, CaVβ1 is expressed in [...] Read more.
Voltage-gated Ca2+ channels (VGCCs) are regulated by four CaVβ subunits (CaVβ1–CaVβ4), each showing specific expression patterns in excitable cells. While primarily known for regulating VGCC function, CaVβ proteins also have channel-independent roles, including gene expression modulation. Among these, CaVβ1 is expressed in skeletal muscle as multiple isoforms. The adult isoform, CaVβ1D, localizes at the triad and modulates CaV1 activity during Excitation–Contraction Coupling (ECC). In this study, we investigated the lesser-known embryonic/perinatal CaVβ1 isoforms and their roles in neuromuscular junction (NMJ) formation, maturation, and maintenance. We found that CaVβ1 isoform expression is developmentally regulated through differential promoter activation. Specifically, CaVβ1A is expressed in embryonic muscle and reactivated in denervated adult muscle, alongside the known CaVβ1E isoform. Nerve injury in adult muscle triggers a shift in promoter usage, resulting in re-expression of embryonic/perinatal Cacnb1A and Cacnb1E transcripts. Functional analyses using aneural agrin-induced AChR clustering on primary myotubes demonstrated that these isoforms contribute to NMJ formation. Additionally, their expression during early post-natal development is essential for NMJ maturation and long-term maintenance. These findings reveal previously unrecognized roles of CaVβ1 isoforms beyond VGCC regulation, highlighting their significance in neuromuscular system development and homeostasis. Full article
(This article belongs to the Section Tissues and Organs)
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13 pages, 1537 KiB  
Article
Correlation of SERPINA-1 Gene Over-Expression with Inhibition of Cell Proliferation and Modulation of the Expression of IL-6, Furin, and NSD2 Genes
by Nassim Tassou, Hajar Anibat, Ahmed Tissent and Norddine Habti
Biologics 2025, 5(3), 22; https://doi.org/10.3390/biologics5030022 - 6 Aug 2025
Abstract
Background and Objectives: The cytokine IL-6, methyltransferase NSD2, pro-protein convertase Furin, and growth factor receptor IGF-1R are essential factors in the proliferation of cancer cells. These proteins are involved in the tumor process by generating several cell-signaling pathways. However, the interactions of these [...] Read more.
Background and Objectives: The cytokine IL-6, methyltransferase NSD2, pro-protein convertase Furin, and growth factor receptor IGF-1R are essential factors in the proliferation of cancer cells. These proteins are involved in the tumor process by generating several cell-signaling pathways. However, the interactions of these oncogenic biomarkers, Furin, IL-6, and NSD2, and their links with the inhibitor SERPINA-1 remain largely unknown. Materials and Methods: Cell proliferation is measured by colorimetric and enzymatic methods. The genetic expressions of SERPINA-1, Furin, IL-6, and NSD2 are measured by qRT-PCR, while the expression of IGF-1R on the cell surface is measured by flow cytometry. Results: The proliferation of cells overexpressing SERPINA-1 (JP7pSer+) is decreased by more than 90% compared to control cells (JP7pSer-). The kinetics of the gene expression ratios of Furin, IL-6, and NSD2 show an increase for 48 h, followed by a decrease after 72 h for the three biomarkers in JP7pSer+ cells compared to JP7pSer- cells. The expression of IGF-1R on the cell surface in both cell lines is low, with JP7pSer- cells expressing 1.33 times more IGF-1R than JP7pSer+ cells. Conclusions: These results suggest gene correlations of SERPINA-1 overexpression with decreased cell proliferation and modulation of gene expression of Furin, IL-6, and NSD2. This study should be complemented by molecular transcriptomic and proteomic experiments to better understand the interaction of SERPINA-1 with IL-6, Furin, and NSD2, and their effect on tumor progression. Full article
(This article belongs to the Topic Advances in Anti-Cancer Drugs: 2nd Edition)
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16 pages, 1298 KiB  
Article
Genetic Effects of Chicken Pre-miR-3528 SNP on Growth Performance, Meat Quality Traits, and Serum Enzyme Activities
by Jianzhou Shi, Jinbing Zhao, Bingxue Dong, Na Li, Lunguang Yao and Guirong Sun
Animals 2025, 15(15), 2300; https://doi.org/10.3390/ani15152300 - 6 Aug 2025
Abstract
The aim was to investigate the genetic effects of a SNP located in the precursor region of gga-miR-3528. (1) Single-nucleotide polymorphisms within precursor regions of microRNAs play crucial biological roles. (2) Utilizing a Gushi–Anka F2 resource population (n = 860), [...] Read more.
The aim was to investigate the genetic effects of a SNP located in the precursor region of gga-miR-3528. (1) Single-nucleotide polymorphisms within precursor regions of microRNAs play crucial biological roles. (2) Utilizing a Gushi–Anka F2 resource population (n = 860), we screened and validated miRNA SNPs. A SNP mutation in the miR-3528 precursor region was identified. Specific primers were designed to amplify the polymorphic fragment. Genotyping was performed for this individual SNP across the population, using the MassArray system. Association analyses were conducted between this SNP and chicken growth and body measurement traits, carcass traits, meat quality traits, and serum enzyme activities. (3) The rs14098602 (+12 bp A > G) was identified within the precursor region of gga-miR-3528. Significant associations (p < 0.05) were observed between this SNP and chicken growth traits (body weight at the age of 0 day, body weight at the age of 2 weeks, and body weight at the age of 4 weeks), carcass traits (evisceration weight), meat quality traits (subcutaneous fat rate and pectoral muscle density), and serum enzyme activities (total protein, albumin, globulin, cholinesterase, and lactate dehydrogenase). (4) These findings suggest that the polymorphism at rs14098602 may influence chicken growth, meat quality, and serum biochemical indices, through specific mechanisms. The gga-miR-3528 gene likely plays an important role in chicken development. Therefore, this SNP can serve as a molecular marker for genetic breeding and auxiliary selection of growth-related traits, facilitating the rapid establishment of elite chicken populations with superior genetic resources. Full article
(This article belongs to the Section Poultry)
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12 pages, 1706 KiB  
Article
Modulating Enzyme–Ligand Binding with External Fields
by Pedro Ojeda-May
Biophysica 2025, 5(3), 33; https://doi.org/10.3390/biophysica5030033 - 6 Aug 2025
Abstract
Protein enzymes are highly efficient catalysts that exhibit adaptability and selectivity under diverse biological conditions. In some organisms, such as bacteria, structurally similar enzymes, for instance, shikimate kinase (SK) and adenylate kinase (AK), coexist and act on chemically related ligands. This raises the [...] Read more.
Protein enzymes are highly efficient catalysts that exhibit adaptability and selectivity under diverse biological conditions. In some organisms, such as bacteria, structurally similar enzymes, for instance, shikimate kinase (SK) and adenylate kinase (AK), coexist and act on chemically related ligands. This raises the question of whether these enzymes can accommodate and potentially react with each other’s ligands. In this study, we investigate the stability of non-cognate ligand binding in SK and explore whether external electric fields (EFs) can modulate this interaction, leading to cross-reactivity in SK. Using molecular dynamics simulations, we assess the structural integrity of SK and the binding behavior of ATP and AMP under EF-off and EF-on cases. Our results show that EFs enhance protein structure stability, stabilize non-cognate ligands in the binding pocket, and reduce local energetic frustration near the R116 residue located in the binding site. In addition to this, dimensionality reduction analyses reveal that EFs induce more coherent protein motions and reduce the number of metastable states. Together, these findings suggest that external EFs can reshape enzyme–ligand interactions and may serve as a tool to modulate enzymatic specificity and functional promiscuity. Thus, we provide computational evidence that supports the concept of using an EF as a tunable parameter in enzyme engineering and synthetic biology. However, further experimental investigation would be valuable to assess the reliability of our computational predictions. Full article
(This article belongs to the Collection Feature Papers in Biophysics)
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25 pages, 8901 KiB  
Article
Purified Cornel Iridoid Glycosides Attenuated Oxidative Stress Induced by Cerebral Ischemia-Reperfusion Injury via Morroniside and Loganin Targeting Nrf2/NQO-1/HO-1 Signaling Pathway
by Zhaoyang Wang, Fangli Xue, Enjie Hu, Yourui Wang, Huiliang Li and Boling Qiao
Cells 2025, 14(15), 1205; https://doi.org/10.3390/cells14151205 - 6 Aug 2025
Abstract
Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and [...] Read more.
Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H2O2-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H2O2-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article
(This article belongs to the Section Cell Signaling)
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21 pages, 3744 KiB  
Article
Gestation-Stage Related Changes in the IGF System Components in the Equine Placenta
by Kirsten E. Scoggin, Fatma Adlan, Carleigh E. Fedorka, Shimaa I. Rakha, Tom A. E. Stout, Mats H. T. Troedsson and Hossam El-Sheikh Ali
Biomolecules 2025, 15(8), 1135; https://doi.org/10.3390/biom15081135 - 6 Aug 2025
Abstract
The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth [...] Read more.
The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth factor (VEGF) expression. The current study investigated the expression of the IGF system components, namely the ligands (IGF1 and IGF2), their receptors (IGF1R, IGF2R, and INSR), and their binding proteins (IGFBPs and IGF2BPs) in equine CA at 45 days, 4, 6, 10, and 11 months of gestational age (GA) and immediately postpartum (PP), and in equine EN at 4, 6, 10, and 11 months GA. IGF1 immunolocalization and serum concentrations were also evaluated across gestation. IGF1 mRNA expression in CA increased from day 45 to peak at 6 months and then gradually declined to reach a nadir in PP samples. This profile correlated positively with the VEGF expression profile (r = 0.62, p = 0.001). In contrast, IGF2 expression in CA was not correlated with VEGF (p = 0.14). Interestingly, IGF2 mRNA was more abundant in equine CA than IGF1 (p < 0.05) throughout gestation. Among the IGFBPs investigated in CA, the expression of IGFBP2 and IGF2BP2 was highly abundant (p < 0.05) at day 45 compared to other GAs. Conversely, mRNA expression for IGFBP3 and IGFBP5 was more abundant (p < 0.05) in PP than at all investigated GAs. Immunohistochemistry revealed that IGF1 is localized in the equine chorionic epithelium (cytoplasm and nucleus). IGF1 serum concentrations peaked at 9 months and declined to their lowest levels PP. In conclusion, this study demonstrates a positive correlation between IGF1 and VEGF expression in equine CA during gestation, suggesting that the IGF system plays a crucial role in placental angiogenesis by regulating VEGF. Full article
(This article belongs to the Section Molecular Biology)
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17 pages, 8134 KiB  
Article
Chronic Low Back Pain in Young Adults: Pathophysiological Aspects of Neuroinflammation and Degeneration
by Natalya G. Pravdyuk, Anastasiia A. Buianova, Anna V. Novikova, Alesya A. Klimenko, Mikhail A. Ignatyuk, Liubov A. Malykhina, Olga I. Patsap, Dmitrii A. Atiakshin, Vitaliy V. Timofeev and Nadezhda A. Shostak
Int. J. Mol. Sci. 2025, 26(15), 7592; https://doi.org/10.3390/ijms26157592 - 6 Aug 2025
Abstract
Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] [...] Read more.
Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] years) with herniated discs and LBP, alongside healthy controls, to investigate changes in the extracellular matrix (ECM) and neurochemical alterations. Disc degeneration was assessed using MRI (Pfirrmann grading) and histology (Sive’s criteria). Histochemical and immunohistochemical methods were used to evaluate aggrecan content, calcification, and the expression of nerve growth factor (NGF), substance P (SP), and S-100 protein. MRI findings included Pfirrmann grades V (30.55%), IV (61.11%), III (5.56%), and II (2.78%). Severe histological degeneration (10–12 points) was observed in three patients. Aggrecan depletion correlated with longer pain duration (r = 0.449, p = 0.031). NGF expression was significantly elevated in degenerated discs (p = 0.0287) and strongly correlated with SP (r = 0.785, p = 5.268 × 10−9). Free nerve endings were identified in 5 cases. ECM calcification, present in 36.1% of patients, was significantly associated with radiculopathy (r = 0.664, p = 0.005). The observed co-localization of NGF and SP suggests a synergistic role in pain development. These results indicate that in young individuals, aggrecan loss, neurochemical imbalance, and ECM calcification are key contributors to DDD and chronic LBP. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Intervertebral Disc Disease)
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20 pages, 7055 KiB  
Article
Cardiopulmonary Bypass-Induced IL-17A Aggravates Caspase-12-Dependent Neuronal Apoptosis Through the Act1-IRE1-JNK1 Pathway
by Ruixue Zhao, Yajun Ma, Shujuan Li and Junfa Li
Biomolecules 2025, 15(8), 1134; https://doi.org/10.3390/biom15081134 - 6 Aug 2025
Abstract
Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen–glucose [...] Read more.
Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen–glucose deprivation/reoxygenation (OGD/R) cellular model, we demonstrated that IL-17A levels were markedly elevated in the hippocampus post-CPB, correlating with endoplasmic reticulum stress (ERS)-mediated apoptosis. Transcriptomic analysis revealed the enrichment of IL-17 signaling and apoptosis-related pathways. IL-17A-Neutralizing monoclonal antibody (mAb) and the ERS inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuated neurological deficits and hippocampal neuronal damage. Mechanistically, IL-17A activated the Act1-IRE1-JNK1 axis, wherein heat shock protein 90 (Hsp90) competitively regulated Act1-IRE1 interactions. Co-immunoprecipitation confirmed the enhanced Hsp90-Act1 binding post-CPB, promoting IRE1 phosphorylation and downstream caspase-12 activation. In vitro, IL-17A exacerbated OGD/R-induced apoptosis via IRE1-JNK1 signaling, reversible by IRE1 inhibition. These findings identify the hippocampus as a key vulnerable region and delineate a novel IL-17A/Act1-IRE1-JNK1 pathway driving ERS-dependent apoptosis. Targeting IL-17A or Hsp90-mediated chaperone switching represents a promising therapeutic strategy for CPB-associated neuroprotection. This study provides critical insights into the molecular crosstalk between systemic inflammation and neuronal stress responses during cardiac surgery. Full article
(This article belongs to the Section Molecular Medicine)
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13 pages, 2106 KiB  
Article
Diagnosis of the Multiepitope Protein rMELEISH3 for Canine Visceral Leishmaniasis
by Rita Alaide Leandro Rodrigues, Mariana Teixeira de Faria, Isadora Braga Gandra, Juliana Martins Machado, Ana Alice Maia Gonçalves, Daniel Ferreira Lair, Diana Souza de Oliveira, Lucilene Aparecida Resende, Maykelin Fuentes Zaldívar, Ronaldo Alves Pinto Nagem, Rodolfo Cordeiro Giunchetti, Alexsandro Sobreira Galdino and Eduardo Sergio da Silva
Appl. Sci. 2025, 15(15), 8683; https://doi.org/10.3390/app15158683 - 6 Aug 2025
Abstract
Canine visceral leishmaniasis (CVL) is a major zoonosis that poses a growing challenge to public health services, as successful disease management requires sensitive, specific, and rapid diagnostic methods capable of identifying infected animals even at a subclinical level. The objective of this study [...] Read more.
Canine visceral leishmaniasis (CVL) is a major zoonosis that poses a growing challenge to public health services, as successful disease management requires sensitive, specific, and rapid diagnostic methods capable of identifying infected animals even at a subclinical level. The objective of this study was to evaluate the performance of the recombinant chimeric protein rMELEISH3 as an antigen in ELISA assays for the robust diagnosis of CVL. The protein was expressed in a bacterial system, purified by affinity chromatography, and evaluated through a series of serological assays using serum samples from dogs infected with Leishmania infantum. ROC curve analysis revealed a diagnostic sensitivity of 96.4%, a specificity of 100%, and an area under the curve of 0.996, indicating excellent discriminatory power. Furthermore, rMELEISH3 was recognized by antibodies present in the serum of dogs with low parasite loads, reinforcing the diagnostic potential of the assay in asymptomatic cases. It is concluded that the use of the recombinant antigen rMELEISH3 could significantly contribute to the improvement of CVL surveillance and control programs in endemic areas of Brazil and other countries, by offering a safe, reproducible and effective alternative to the methods currently recommended for the serological diagnosis of the disease. Full article
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9 pages, 391 KiB  
Article
Meconium and Amniotic Fluid IgG Fc Binding Protein (FcGBP) Concentrations in Neonates Delivered by Cesarean Section and by Vaginal Birth in the Third Trimester of Pregnancy
by Barbara Lisowska-Myjak, Kamil Szczepanik, Ewa Skarżyńska and Artur Jakimiuk
Int. J. Mol. Sci. 2025, 26(15), 7579; https://doi.org/10.3390/ijms26157579 - 5 Aug 2025
Abstract
IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide [...] Read more.
IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide new knowledge of the mechanisms responsible for the immune adaptation of the fetus to extrauterine life. FcGBP concentrations were measured by ELISA in the first-pass meconium and amniotic fluid samples collected from 120 healthy neonates delivered by either vaginal birth (n = 35) or cesarean section (n = 85) at 36 to 41 weeks gestation. The meconium FcGBP concentrations (405.78 ± 145.22 ng/g) decreased (r = −0.241, p = 0.007) over the course of 36 to 41 weeks gestation, but there were no significant changes (p > 0.05) in the amniotic fluid FcGBP (135.70 ± 35.83 ng/mL) in the same period. Both meconium and amniotic fluid FcGBP concentrations were higher (p < 0.05) in neonates delivered by cesarean section. Decreases in the meconium FcGBP concentrations correlated (r = −0.37, p = 0.027) with the gestational age in neonates delivered by vaginal birth but not in those delivered by cesarean section (p > 0.05). No association was found between the FcGBP concentrations in meconium and amniotic fluid and the birth weight (p > 0.05). With the development of the mucosal immune system in the fetal intestine over the course of the third trimester of gestation, the meconium FcGBP concentrations decrease. Increased FcGBP concentrations measured in the meconium and amniotic fluid of neonates delivered by cesarean section may possibly indicate altered intestinal mucosal function. Intrauterine growth is not associated with the intestinal mucosal barrier maturation involving FcGBP. Full article
(This article belongs to the Special Issue Female Infertility and Fertility)
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