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Keywords = α1-Na/K-ATPase

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19 pages, 15448 KiB  
Article
Adverse Effects of Glyphosate and Microcystin-LR on Fish Health: Evidence from Structural and Functional Impairments in Zebrafish Gills
by Yidan Zhang, Han Hu, Linmei Song, Zhihui Liu, Junguo Ma and Xiaoyu Li
Animals 2025, 15(16), 2355; https://doi.org/10.3390/ani15162355 - 11 Aug 2025
Viewed by 288
Abstract
Glyphosate (GLY) and microcystin-LR (MC-LR) frequently co-occur in natural water bodies. In this study, a subacute exposure test was conducted on zebrafish treated with 3.5 mg/L GLY and 35 μg/L MC-LR, individually and in combination, for 21 d to determine their effects on [...] Read more.
Glyphosate (GLY) and microcystin-LR (MC-LR) frequently co-occur in natural water bodies. In this study, a subacute exposure test was conducted on zebrafish treated with 3.5 mg/L GLY and 35 μg/L MC-LR, individually and in combination, for 21 d to determine their effects on the gills of zebrafish and their potential mechanisms. The hematoxylin and eosin staining and scanning electron microscopy examination results showed that GLY and MC-LR exposure caused structural damage to gills. Biochemical analysis revealed Na+-K+-ATPase activity decreased, and the levels of reactive oxygen species, 8-hydroxy-2′-deoxyguanosine, and malondialdehyde increased, inducing oxidative damage to DNA and lipids of gills. Meanwhile, the inflammatory and immune function of the gill was significantly influenced, as evidenced by the alteration of the expression of tumor necrosis factor-α, interleukin-1β, complement 3, and immunoglobulin M. RNA-seq results revealed that GLY and/or MC-LR treatment induced transcriptional changes in the fish gills, which may affect various biological functions, and the lipid metabolism disruption potentially involved in the aforementioned process. Integrating histopathological, biochemical, and transcriptomic analyses, this study revealed that both individual and combined exposures to GLY and MC-LR had adverse effects on zebrafish gills, with combined exposure appears to result in more pronounced adverse effects, potentially compromising fish health. Full article
(This article belongs to the Section Aquatic Animals)
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16 pages, 1287 KiB  
Review
Oxidative Stress in the Regulation of Autosis-Related Proteins
by María Guerra-Andrés, Inés Martínez-Rojo, Alejandra Piedra-Macías, Elena Lavado-Fernández, Marina García-Macia and Álvaro F. Fernández
Antioxidants 2025, 14(8), 958; https://doi.org/10.3390/antiox14080958 - 4 Aug 2025
Viewed by 415
Abstract
Physiological levels of reactive oxygen species (ROS) play a crucial role as intracellular signaling molecules, helping to maintain cellular homeostasis. However, when ROS accumulate excessively, they become toxic to cells, leading to damage to lipids, proteins, and DNA. This oxidative stress can impair [...] Read more.
Physiological levels of reactive oxygen species (ROS) play a crucial role as intracellular signaling molecules, helping to maintain cellular homeostasis. However, when ROS accumulate excessively, they become toxic to cells, leading to damage to lipids, proteins, and DNA. This oxidative stress can impair cellular function and lead to various forms of cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis. Despite their significance, the role of ROS in autosis (an autophagy-dependent form of cell death) remains largely unexplored. In this review, we gather current knowledge on autotic cell death and summarize how oxidative stress influences the activity of Beclin-1 and the Na+,K+-ATPase pump, both of which are critical effectors of this pathway. Finally, we discuss the theoretical potential for ROS to modulate this type of cell death, proposing a possible dual role for these species in autosis regulation through effectors such as HIF-1α, TFEB, or the FOXO family, and highlighting the need to experimentally address cellular redox status when working on autotic cell death. Full article
(This article belongs to the Special Issue Crosstalk between Autophagy and Oxidative Stress)
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20 pages, 2847 KiB  
Article
Oxidative Stress Disrupts Gill Function in Eriocheir sinensis: Consequences for Ion Transport, Apoptosis, and Autophagy
by Wenrong Feng, Qinghong He, Qiqin Yang, Yuanfeng Xu, Gang Jiang, Jianlin Li, Jun Zhou, Rui Jia and Yongkai Tang
Antioxidants 2025, 14(8), 897; https://doi.org/10.3390/antiox14080897 - 22 Jul 2025
Viewed by 393
Abstract
Oxidative stress is a key mediator of physiological dysfunction in aquatic organisms under environmental challenges, yet its comprehensive impacts on gill physiology require further clarification. This study investigated the molecular and cellular responses of Eriocheir sinensis gills to hydrogen peroxide (H2O [...] Read more.
Oxidative stress is a key mediator of physiological dysfunction in aquatic organisms under environmental challenges, yet its comprehensive impacts on gill physiology require further clarification. This study investigated the molecular and cellular responses of Eriocheir sinensis gills to hydrogen peroxide (H2O2)-induced oxidative stress, integrating antioxidant defense, ion transport regulation, and stress-induced cell apoptosis and autophagy. Morphological alterations in the gill filaments were observed, characterized by septum degeneration, accumulation of haemolymph cells, and pronounced swelling. For antioxidant enzymes like catalase (CAT) and glutathione peroxidase (GPx), activities were enhanced, while superoxide dismutase (SOD) activity was reduced following 48 h of exposure. Overall, the total antioxidant capacity (T-AOC) showed a significant increase. The elevated concentrations of malondialdehyde (MDA) and H2O2 indicated oxidative stress. Ion transport genes displayed distinct transcription patterns: Na+-K+-2Cl co-transporter-1 (NKCC1), Na+/H+ exchanger 3 (NHE3), aquaporin 7 (AQP7), and chloride channel protein 2 (CLC2) were significantly upregulated; the α-subunit of Na+/K+-ATPase (NKAα) and carbonic anhydrase (CA) displayed an initial increase followed by decline; whereas vacuolar-type ATPase (VATP) consistently decreased, suggesting compensatory mechanisms to maintain osmotic balance. Concurrently, H2O2 triggered apoptosis (Bcl2, Caspase-3/8) and autophagy (beclin-1, ATG7), likely mediated by MAPK and AMPK signaling pathways. These findings reveal a coordinated yet adaptive response of crab gills to oxidative stress, providing new insights into the mechanistic basis of environmental stress tolerance in crustaceans. Full article
(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—2nd Edition)
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18 pages, 3304 KiB  
Article
Enhancement of Hypoxia Tolerance of Gibel Carp (Carassius auratus gibelio) via a Ferroporphyrin-Rich Diet
by Hualiang Liang, Haifeng Mi, Kai Wang, Mingchun Ren, Lu Zhang, Dongyu Huang and Jiaze Gu
Antioxidants 2025, 14(6), 738; https://doi.org/10.3390/antiox14060738 - 16 Jun 2025
Viewed by 646
Abstract
Gibel carp (Carassius auratus gibelio) were hypoxia stressed for 12 h after an 8-week FPR nutrient-enriched feeding experiment, which was to evaluate the role of FPR in hypoxic stress in gibel carp (Carassius auratus gibelio). The dissolved oxygen was [...] Read more.
Gibel carp (Carassius auratus gibelio) were hypoxia stressed for 12 h after an 8-week FPR nutrient-enriched feeding experiment, which was to evaluate the role of FPR in hypoxic stress in gibel carp (Carassius auratus gibelio). The dissolved oxygen was reduced to a range of 0.6 ± 0.2 mg/L. Results showed that FPR supplementation could maintain the osmotic pressure equilibrium by improving the ion concentrations of plasma including Na+, Ca+ and K+, and Na+/K+-ATPase activity of liver. FPR supplementation could effectively enhance the antioxidant capacity by improving the levels of GPX, SOD, CAT, and GSH, and reduce the level of MDA. FPR supplementation could improve the core gene expressions of Nrf2 signalling pathway including nrf2, sod, ho-1, gpx, and cat. The high levels of FPR supplementation (0.04%) might had a negative effect on immunity. FPR supplementation could improve the expression levels of HIF-1 signalling pathway-related genes to adapt to hypoxia condition including hif-1α, epo, angpt1, vegf, et1, and tfr-1. These results also were supported by higher SR and number of gill mitochondria in FPR supplementation. In general, the appropriate FPR supplementation was 0.01% based on the results of this study and economic cost, which could heighten hypoxic adaptation and SR. Full article
(This article belongs to the Special Issue Antioxidants Benefits in Aquaculture—3rd Edition)
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34 pages, 2415 KiB  
Article
Strategies to Develop Na,K-ATPase-α4 Inhibitors as Male Contraceptives
by Shameem S. Syeda, Gladis Sánchez, Jeffrey P. McDermott, Narsihmulu Cheryala, Henry L. Wong, Gunda I. Georg and Gustavo Blanco
Int. J. Mol. Sci. 2025, 26(12), 5646; https://doi.org/10.3390/ijms26125646 - 12 Jun 2025
Viewed by 996
Abstract
Male contraception remains an unmet need. Na,K-ATPase α4 (NKA α4), a specific Na⁺/K⁺ transporter of the sperm flagellum, is an attractive target for male contraception. NKA α4 is critical for sperm motility and fertility, and its deletion in male mice causes complete infertility. [...] Read more.
Male contraception remains an unmet need. Na,K-ATPase α4 (NKA α4), a specific Na⁺/K⁺ transporter of the sperm flagellum, is an attractive target for male contraception. NKA α4 is critical for sperm motility and fertility, and its deletion in male mice causes complete infertility. Our previous structure–activity relationship (SAR) studies on a cardenolide scaffold identified a highly selective, safe NKAα4 inhibitor, but its complex, heavily hydroxylated structure posed challenges for modification and optimization. To address this, we employed a structural simplification strategy to synthesize novel steroidal and non-steroidal analogs and examined their effects on NKAα4 inhibition and sperm motility. Both series reduced sperm motility (up to ~50%), with IC50 values in the picomolar range. Compounds 13 and 45 displayed specificities for NKAα4 over NKAα1, did not affect sperm viability, and showed no reversibility in vitro. Notably, 45, featuring a hexahydronaphthalene core and a benzyltriazole moiety at C5, exhibited potent, highly selective NKAα4 inhibition, reduced sperm motility in vitro and in vivo, and blocked fertilization in vitro. This highlights 45 as a promising lead for non-hormonal male contraception and indicates that the newly generated series of compounds possess the key characteristics needed for further development as potential non-hormonal male contraceptive agents. Full article
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18 pages, 12274 KiB  
Article
Atp1b2Atp1b1 Knock-In Mice Exhibit a Cone–Rod Dystrophy-Like Phenotype
by Susanne Bartsch, Yevgeniya Atiskova, Stefanie Schlichting, Elke Becker, Maike Herrmann and Udo Bartsch
Cells 2025, 14(12), 878; https://doi.org/10.3390/cells14120878 - 11 Jun 2025
Viewed by 716
Abstract
The Na,K-ATPase is a heterodimeric ion pump consisting of various combinations of a catalytic α-subunit (α1, α2, α3, or α4, encoded by ATP1A1–ATP1A4) and a β-subunit (β1, β2, or β3, encoded by ATP1B1–ATP1B3). We have previously shown that Atp1b2 knock-out (ko) [...] Read more.
The Na,K-ATPase is a heterodimeric ion pump consisting of various combinations of a catalytic α-subunit (α1, α2, α3, or α4, encoded by ATP1A1–ATP1A4) and a β-subunit (β1, β2, or β3, encoded by ATP1B1–ATP1B3). We have previously shown that Atp1b2 knock-out (ko) mice exhibit rapid photoreceptor cell degeneration, whereas Atp1b2Atp1b1 knock-in (ki) mice, which express the β1-subunit instead of the β2-subunit under regulatory elements of the Atp1b2 gene, exhibit slowly progressive retinal dystrophy. Here, we performed a detailed analysis of the retinal phenotype of the Atp1b2Atp1b1 ki mouse. We found that the number of cone photoreceptor cells in the mutant retinas was significantly reduced by postnatal day 28. The retinas of 4-month-old mice were almost devoid of cones. The early onset and rapid loss of cones was followed by a slowly progressive degeneration of rods. Other retinal cell types were unaffected. Nonradioactive in situ hybridization and immunohistochemistry revealed that wild-type photoreceptors expressed β3 and high levels of β2, while Atp1b2Atp1b1 ki photoreceptor cells expressed β3 and low levels of transgenic β1. Additionally, levels of retinoschisin, a secreted retina-specific protein that interacts directly with the β2-subunit, were greatly reduced in mutant retinas. The results demonstrate that the β1-subunit can functionally compensate, at least in part, for the absence of the β2-subunit. The results also show that cones are more susceptible to Na,K-ATPase dysfunction than rods. Taken together, the present study identifies the Atp1b2Atp1b1 ki mutant as a novel animal model of an early-onset and rapidly progressive cone–rod dystrophy. Full article
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21 pages, 10060 KiB  
Article
The Effects of the Natriuretic Peptide System on Alveolar Epithelium in Heart Failure
by Yara Knany, Safa Kinaneh, Emad E. Khoury, Yaniv Zohar, Zaid Abassi and Zaher S. Azzam
Int. J. Mol. Sci. 2025, 26(7), 3374; https://doi.org/10.3390/ijms26073374 - 4 Apr 2025
Viewed by 638
Abstract
Alveolar active sodium transport is essential for clearing edema from airspaces, in a process known as alveolar fluid clearance (AFC). Although it has been reported that atrial natriuretic peptide (ANP) attenuates AFC, little is known about the underlying molecular effects of natriuretic peptides [...] Read more.
Alveolar active sodium transport is essential for clearing edema from airspaces, in a process known as alveolar fluid clearance (AFC). Although it has been reported that atrial natriuretic peptide (ANP) attenuates AFC, little is known about the underlying molecular effects of natriuretic peptides (NPs). Therefore, we examined the contribution of NPs to AFC and their effects as mediators of active sodium transport. By using the isolated liquid-filled lungs model, we investigated the effects of NPs on AFC. The expression of NPs, Na+, K+-ATPase, and Na+ channels was assessed in alveolar epithelial cells. Congestive heart failure (CHF) was induced by using the aortocaval fistula model. ANP and brain NP (BNP) significantly reduced AFC rate from 0.49 ± 0.02 mL/h in sham rats to 0.26 ± 0.013 and 0.19 ± 0.005 in ANP and BNP-treated groups, respectively. These effects were mediated by downregulating the active Na+ transport components in the alveolar epithelium while enhancing the ubiquitination and degradation of αENaC in the lungs, as reflected by increased levels of Nedd4-2. In addition, AFC was reduced in compensated CHF rats treated with ANP, while in decompensated CHF, ANP partially restored AFC. In conclusion, NPs regulate AFC in health and CHF. This research could help optimize pharmacological treatments for severe CHF. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Lung Health and Disease)
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20 pages, 4509 KiB  
Article
Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides—A Unique Role of the Alpha3 Isoform of the Na+/K+-ATPase Pump
by Hong Mei, Hongyi Cai, Fengjie Liu, Rajkumar Venkatadri, Halli E. Miller, Angela J. Mathison, Hua-Yu Leo Wang, Simone C. Silva, George A. O’Doherty and Ravit Arav-Boger
Viruses 2025, 17(3), 398; https://doi.org/10.3390/v17030398 - 11 Mar 2025
Viewed by 872
Abstract
Cardiac glycosides (CGs), historically used to treat heart failure and arrhythmias, bind to the α subunit of the Na+/K+-ATPase pump and inhibit its activity. Their anticancer and antiviral activities are of interest. The α subunit of the Na+ [...] Read more.
Cardiac glycosides (CGs), historically used to treat heart failure and arrhythmias, bind to the α subunit of the Na+/K+-ATPase pump and inhibit its activity. Their anticancer and antiviral activities are of interest. The α subunit of the Na+/K+-ATPase pump has four isoforms (α1–4), each with unique tissue distribution and expression pattern; their contributions to antiviral activities have not been studied. We previously reported that CGs inhibit human CMV (HCMV) in vitro but not mouse CMV (MCMV). In addition to the low affinity of mouse α1 for CGs, we hypothesized that other isoforms contribute to the anti-CMV activities of CGs. We show here that infection with HCMV significantly induced α3 in human foreskin fibroblasts, while MCMV did not induce mouse α3. Infection with guinea pig CMV (GPCMV) in GP fibroblasts also induced α3, and CGs inhibited GPCMV replication. HCMV inhibition with digitoxin reduced α3 expression. The concentration-dependent inhibition of HCMV with digitoxin analogs also correlated with α3 expression. Intriguingly, α3 was localized to the nucleus, and changes in its expression during infection and digitoxin treatment were mostly limited to the nucleus. At 4 h post-infection, α3 colocalized with immediate early 1 (IE1) and the promyelocytic leukemia protein (PML). An interaction of α3-PML-IE1 at 24 h post-infection was disrupted by digitoxin. The mRNA levels of IE1, major immediate early promoter (MIEP)-derived IE, and antiviral cytokines were reduced in infected digitoxin-treated cells. Summarized, these findings suggest a new role for α3 in the anti-HCMV activities of CGs via nuclear antiviral signaling pathways. Full article
(This article belongs to the Special Issue Molecular Biology of Human Cytomegalovirus)
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17 pages, 1020 KiB  
Article
The Significant Enhancing Effect of Vitamin B6-Fortified Feed on the Intestinal Digestive Efficiency, Immunity, and Antioxidant Defense Mechanisms of Juvenile Largemouth Bass (Micropterus salmoides)
by Leimin Zhang, Dongyu Huang, Jiaze Gu, Hualiang Liang and Mingchun Ren
Antioxidants 2025, 14(3), 313; https://doi.org/10.3390/antiox14030313 - 5 Mar 2025
Cited by 2 | Viewed by 991
Abstract
A 12-week aquaculture trial was conducted to evaluate the effects of vitamin B6 on the intestinal health of largemouth bass (Micropterus salmoides). Six feeds with a vitamin B6 content of 2.03 (control group), 2.91, 3.30, 6.03, 9.53, and 21.79 [...] Read more.
A 12-week aquaculture trial was conducted to evaluate the effects of vitamin B6 on the intestinal health of largemouth bass (Micropterus salmoides). Six feeds with a vitamin B6 content of 2.03 (control group), 2.91, 3.30, 6.03, 9.53, and 21.79 mg/kg were prepared. The results were as follows. Regarding digestive efficiency, the 9.53 mg/kg group showed significantly higher activities of AMY, LPS, and TRY compared to the control group; the 6.03 mg/kg group exhibited increased AKP and Na+/K+ ATPase activities. Regarding immunity, the 6.03 mg/kg group had markedly higher relative expressions of zo-1 and occ than the control group; the 9.53 mg/kg group showed significantly higher relative expressions of il-10, tgf-β, igm, and cd83, while il-8 and tnf-α were notably lower, and nf-κb was noticeably decreased in 21.79 mg/kg group. For antioxidant capacity, the 6.03 mg/kg group had markedly higher activities of CAT, SOD, GSH-Px, and T-AOC levels, compared to the control group; the MDA level in the control group was markedly higher than in the other groups. The relative expressions of nrf2, cat, Cu-Zn sod, and gpx were highest in 9.53 mg/kg group and significantly higher than in the control group. In conclusion, an appropriate level of vitamin B6 in the feed is vital for protecting the intestinal health of largemouth bass. Full article
(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—2nd Edition)
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24 pages, 5714 KiB  
Article
Iron Overload-Related Oxidative Stress Leads to Hyperphosphorylation and Altered Anion Exchanger 1 (Band 3) Function in Erythrocytes from Subjects with β-Thalassemia Minor
by Sara Spinelli, Elisabetta Straface, Lucrezia Gambardella, Daniele Caruso, Silvia Dossena, Angela Marino, Rossana Morabito and Alessia Remigante
Int. J. Mol. Sci. 2025, 26(4), 1593; https://doi.org/10.3390/ijms26041593 - 13 Feb 2025
Cited by 1 | Viewed by 1224
Abstract
β-thalassemia, a hereditary hemoglobinopathy, is caused by reduced or absent synthesis of the β-globin chains of hemoglobin. Three clinical conditions are recognized: β-thalassemia major, β-thalassemia intermedia, and β-thalassemia minor (β-Thal+). This latter condition occurs when an individual inherits a mutated β-globin [...] Read more.
β-thalassemia, a hereditary hemoglobinopathy, is caused by reduced or absent synthesis of the β-globin chains of hemoglobin. Three clinical conditions are recognized: β-thalassemia major, β-thalassemia intermedia, and β-thalassemia minor (β-Thal+). This latter condition occurs when an individual inherits a mutated β-globin gene from one parent. In erythrocytes from β-Thal+ subjects, the excess α-globin chains produce unstable α-tetramers, which can induce substantial oxidative stress leading to plasma membrane and cytoskeleton damage, as well as deranged cellular function. In the present study, we hypothesized that increased oxidative stress might lead to structural rearrangements in erythrocytes from β-Thal+ volunteers and functional alterations of ion transport proteins, including band 3 protein. The data obtained showed significant modifications of the cellular shape in erythrocytes from β-Thal+ subjects. In particular, a significantly increased number of elliptocytes was observed. Interestingly, iron overload, detected in erythrocytes from β-Thal+ subjects, provoked a significant production of reactive oxygen species (ROS), overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase, and glutathione depletion, resulting in (a) increased lipid peroxidation, (b) protein sulfhydryl group (-SH) oxidation. Iron overload-related oxidative stress affected Na+/K+-ATPase activity, which in turn may have contributed to impaired β-Thal+ erythrocyte deformability. As a result, alterations in the distribution of cytoskeletal proteins, including α/β-spectrin, protein 4.1, and α-actin, in erythrocytes from β-Thal+ subjects have been detected. Significantly, oxidative stress was also associated with increased phosphorylation and altered band 3 ion transport activity, as well as increased oxidized hemoglobin, which led to abnormal clustering and redistribution of band 3 on the plasma membrane. Taken together, these findings contribute to elucidating potential oxidative stress-related perturbations of ion transporters and associated cytoskeletal proteins, which may affect erythrocyte and systemic homeostasis in β-Thal+ subjects. Full article
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15 pages, 6963 KiB  
Article
Chemical Composition and Antimicrobial Activity of Essential Oil of Camphora glanduliferum ‘Honganzhang’
by Yang Yang, Qiuting Xiang, Yinan Yang, Donglv Shu, Jiawen Yan, Lijun Huang, Xiumei Yang, Jing Peng, Xingliang Chen and Guoqun Yang
Horticulturae 2025, 11(1), 67; https://doi.org/10.3390/horticulturae11010067 - 10 Jan 2025
Cited by 3 | Viewed by 1217
Abstract
As an excellent variety of Camphora glanduliferum, Honganzhang has high essential oil content and can be used as industrial and pharmaceutical raw materials to extract essential oil, which has high development value. In this study, fresh branches and leaves of C. glanduliferum [...] Read more.
As an excellent variety of Camphora glanduliferum, Honganzhang has high essential oil content and can be used as industrial and pharmaceutical raw materials to extract essential oil, which has high development value. In this study, fresh branches and leaves of C. glanduliferum ’Honganzhang’ were used as materials. After extracting C. glanduliferum ’Honganzhang’ essential oils (CGHEO) by steam distillation, gas chromatography-mass spectrometry (GC-MS) was used to analyze its chemical components. On this basis, the antibacterial effect of CGHEO and its potential physiological mechanism were further explored. The results showed that the main components of CGHEO were Cineole (46.57%), α-terpineol (9.93%), Sabinene (8.02%), β-terpinene (6.04%), and α-pinene (4.49%), these compounds can be used in medicine, food and other industries. In terms of antibacterial effect, CGHEO has significant antibacterial effects on three Gram-negative bacteria (Escherichia coli, Salmonella enteritidis, and Pseudomonas aeruginosa), and two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus). CGHEO can reduce Na+K+-ATPase activity and SDH activity and further interfere with the operation of the bacterial respiratory chain, thereby achieving the effect of inhibiting bacterial reproduction. Based on the main chemical components contained in C. glanduliferum ’Honganzhang’ and its remarkable antibacterial effect, this study is expected to provide a theoretical basis for the wide application of C. glanduliferum ’Honganzhang’ in multiple fields such as medicine, health care, food, and industry. Full article
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17 pages, 2735 KiB  
Article
Effects of Stocking Density on Fatty Acid and Amino Acid Composition in Muscle, Serum Cortisol, Stress and Immune Response in Large Yellow Croaker (Larimichthys crocea)
by Youbin Yu, Liang Wang, Wenyun Huang, Duo Yu, Qiaoxuan Sun and Mingcao Cui
J. Mar. Sci. Eng. 2025, 13(1), 36; https://doi.org/10.3390/jmse13010036 - 29 Dec 2024
Cited by 1 | Viewed by 1167
Abstract
To explore the effect of density on large yellow croaker (Larimichthys crocea) under intensive aquaculture conditions and determine the appropriate culturing density, this study investigate the effects of different stocking densities on the nutritional composition, stress, and immune levels of large [...] Read more.
To explore the effect of density on large yellow croaker (Larimichthys crocea) under intensive aquaculture conditions and determine the appropriate culturing density, this study investigate the effects of different stocking densities on the nutritional composition, stress, and immune levels of large yellow croaker. Through a long-term aquaculture experiment, conducted under flow-through conditions of intensive aquaculture, three initial density groups were set: a low density group [LD], 4.92 kg/m3; a medium density group [MD], 7.56 kg/m3; and a high density group [HD], 10.08 kg/m3, for a 150-day rearing trial. Large yellow croaker were fed to satiation twice daily (6:00, 17:00). At the end of this trial, the final densities were 10.38 ± 0.50, 14.41 ± 1.06, and 18.71 ± 0.99 kg/m3 in the LD, MD, and HD groups, respectively. The results showed that the growth performances were adversely influenced by a high stocking density. Levels of cortisol in serum, superoxide dismutase (SOD) and catalase (CAT) in liver, Na+-K+ ATPase and Na+-K+ ATPase gene in gills, and heat shock protein (HSP70/90) genes and glutathione S-transferase (GST) genes in the liver significantly increased under HD treatment. Results of immune response analyses showed that there was a clear decrease in immunoglobulin M (IgM), complement component 4 (C4), and lysozyme (LZM) in serum, lysozyme (LZM) genes, tumor necrosis factor-alpha (TNF-α) genes and interleukin-1β (IL-1β) genes in the head kidney of large yellow croakers reared in the HD group. An obvious increase in free amino acids and fatty acids in the muscle of large yellow croakers reared in HD group was also observed. Overall, this study showed that the optimal final culturing density of large yellow croaker under flow-through systems should be between 14.41 kg/m3 and 18.71 kg/m3 to improve aquaculture efficiency and product quality. Full article
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14 pages, 9492 KiB  
Article
SIRT1 Activation Suppresses Corneal Endothelial–Mesenchymal Transition via the TGF-β/Smad2/3 Pathway
by Yi Yu, Ruilin Guo, Jie Ling, Chenjia Xu, Minglu Ma, Xiaojuan Dong, Jing Wu and Ting Huang
Curr. Issues Mol. Biol. 2024, 46(12), 13846-13859; https://doi.org/10.3390/cimb46120827 - 6 Dec 2024
Cited by 1 | Viewed by 1363
Abstract
Endothelial–mesenchymal transition (EnMT) is the transversion of endothelial cells to mesenchymal cells under certain physiological or pathological conditions. When EnMT occurs in the corneal endothelium, corneal endothelial cells (CECs) lose their normal function and thus cannot maintain corneal clarity. Studies have shown that [...] Read more.
Endothelial–mesenchymal transition (EnMT) is the transversion of endothelial cells to mesenchymal cells under certain physiological or pathological conditions. When EnMT occurs in the corneal endothelium, corneal endothelial cells (CECs) lose their normal function and thus cannot maintain corneal clarity. Studies have shown that the mechanism of EnMT in CECs involves the transforming growth factor-β (TGF-β) signaling pathway, and one of the important inhibitors of the TGF-β/Smad2/3 pathway is sirtuin-1 (SIRT1). In this study, we used a rat model of corneal endothelium injury and TGF-β1-treated human CECs to induce EnMT, aiming to explore whether SIRT1 activation inhibits corneal EnMT in vivo and in vitro. SIRT1 was activated and suppressed using resveratrol (RSV) and EX527, respectively. The endothelial markers and mesenchymal markers were measured by immunofluorescence and Western blot assays. Co-immunoprecipitation was used to detect the interaction between SIRT1 and Smad2/3. The results showed that after mechanical injury, the group treated with RSV-activated SIRT1 regained corneal transparency and recovered from edema faster than the control group. Moreover, RSV-activated SIRT1 downregulated the expression levels of alpha smooth muscle actin (α-SMA), vimentin, and Snail and upregulated the expression levels of E-cadherin and Na+/K+-ATPase both in vivo and in vitro, but these effects were reversed when SIRT1 was inhibited by EX527. SIRT1 also upregulated the expression levels of TGF-β receptor 1 and phosphorylated Smad2/3. The interaction between SIRT1 and Smad2/3 in vitro was confirmed by co-immunoprecipitation. Overall, our results indicate that SIRT1 activation inhibits corneal EnMT via the TGF-β/Smad2/3 pathway, which may be a potential therapeutic target for corneal endothelium dysfunction. Full article
(This article belongs to the Section Molecular Medicine)
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20 pages, 4799 KiB  
Article
Male Wistar Rats Chronically Fed with a High-Fat Diet Develop Inflammatory and Ionic Transport Angiotensin-(3–4)-Sensitive Myocardial Lesions but Preserve Echocardiographic Parameters
by Thuany Crisóstomo, Rafael Luzes, Matheus Leonardo Lima Gonçalves, Marco Antônio Estrela Pardal, Humberto Muzi-Filho, Glória Costa-Sarmento, Debora B. Mello and Adalberto Vieyra
Int. J. Mol. Sci. 2024, 25(22), 12474; https://doi.org/10.3390/ijms252212474 - 20 Nov 2024
Viewed by 1435
Abstract
The central aim of this study was to investigate whether male Wistar rats chronically fed a high-fat diet (HFD) over 106 days present high levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and Na+ and Ca2+ transport alterations in the [...] Read more.
The central aim of this study was to investigate whether male Wistar rats chronically fed a high-fat diet (HFD) over 106 days present high levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and Na+ and Ca2+ transport alterations in the left ventricle, together with dyslipidemia and decreased glucose tolerance, and to investigate the influence of Ang-(3–4). The rats became moderately overweight with an expansion of visceral adiposity. Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles from plasma and left-ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). IL-6 and TNF-α increased (62% and 53%, respectively), but returned to normal levels with Angiotensin-(3–4) administration after 106 days. Significant lipidogram alterations accompanied a decrease in glucose tolerance. Angiotensin II receptors abundance did not change. (Na+ + K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, but returned to normal values upon Angiotensin-(3–4) administration. SERCA2a lost its ability to respond to excess ATP. Echocardiography showed no changes in FS or EF. We conclude that being overweight causes an increase in Ang-(3–4)-sensitive IL-6 and TNF-α levels, and ion transport alterations in the left ventricle that could evolve into future heart dysfunction. Full article
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13 pages, 2634 KiB  
Article
Molecular Structure of the Na+,K+-ATPase α4β1 Isoform in Its Ouabain-Bound Conformation
by Kazuhiro Abe, Jeff McDermott, Hridya Valia Madapally, Parthiban Marimuthu, Chai C. Gopalasingam, Christoph Gerle, Hideki Shigematsu, Himanshu Khandelia and Gustavo Blanco
Int. J. Mol. Sci. 2024, 25(22), 12397; https://doi.org/10.3390/ijms252212397 - 19 Nov 2024
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Abstract
Na+,K+-ATPase is the active ion transport system that maintains the electrochemical gradients for Na+ and K+ across the plasma membrane of most animal cells. Na+,K+-ATPase is constituted by the association of two major [...] Read more.
Na+,K+-ATPase is the active ion transport system that maintains the electrochemical gradients for Na+ and K+ across the plasma membrane of most animal cells. Na+,K+-ATPase is constituted by the association of two major subunits, a catalytic α and a glycosylated β subunit, both of which exist as different isoforms (in mammals known as α1, α2, α3, α4, β1, β2 and β3). Na+,K+-ATPase α and β isoforms assemble in different combinations to produce various isozymes with tissue specific expression and distinct biochemical properties. Na+,K+-ATPase α4β1 is only found in male germ cells of the testis and is mainly expressed in the sperm flagellum, where it plays a critical role in sperm motility and male fertility. Here, we report the molecular structure of Na+,K+-ATPase α4β1 at 2.37 Å resolution in the ouabain-bound state and in the presence of beryllium fluoride. Overall, Na+,K+-ATPase α4 structure exhibits the basic major domains of a P-Type ATPase, resembling Na+,K+-ATPase α1, but has differences specific to its distinct sequence. Dissimilarities include the site where the inhibitor ouabain binds. Molecular simulations indicate that glycosphingolipids can bind to a putative glycosphingolipid binding site, which could potentially modulate Na+,K+-ATPase α4 activity. This is the first experimental evidence for the structure of Na+,K+-ATPase α4β1. These data provide a template that will aid in better understanding the function Na+,K+-ATPase α4β1 and will be important for the design and development of compounds that can modulate Na+,K+-ATPase α4 activity for the purpose of improving male fertility or to achieve male contraception. Full article
(This article belongs to the Special Issue The Na, K-ATPase in Health and Disease)
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