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Keywords = d-amino acids oxidase

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20 pages, 12384 KiB  
Article
Oxidative Stress Model of Lipopolysaccharide-Challenge in Piglets of Wuzhishan Miniature Pig
by Ruiying Bao, Pingfei Qiu, Yanrong Hu, Junpu Chen, Xiaochun Li, Qin Wang, Yongqiang Li, Huiyu Shi, Haiwen Zhang and Xuemei Wang
Vet. Sci. 2025, 12(8), 694; https://doi.org/10.3390/vetsci12080694 - 24 Jul 2025
Viewed by 234
Abstract
Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided [...] Read more.
Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided into four groups and equally intraperitoneally injected with LPS at doses of 0 μg/kg (control), 50 μg/kg (L-LPS), 100 μg/kg (M-LPS) and 150 μg/kg (H-LPS) body weight, respectively. The results showed that total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and catalase (CAT) were decreased, while malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), diamine oxidase (DAO) and D-lactic acid (D-LA) were increased in the M-LPS and H-LPS group on day 1 in comparison with the control group, but no differences were found among treatments on day 7. However, LPS treatments gave rise to varying degrees of pathological injury in the intestines, livers and spleens on day 7. Metabolomics analysis indicated that compared with the control group, glycyl-valine, histamine and lepidine F were decreased in the M-LPS group. Most differentially expressed metabolites were enriched in amino acid-related metabolism pathways on both day 1 and day 7. Microbiome analysis identified that Oscillibacter_sp._CAG:241 was decreased in the M-LPS group compared with the control group on day 1, while Bacteroides_thetaiotaomicron and Lactobacillus_amylovorus were reduced in the M-LPS group on day 7. Collectively, an LPS dose of 100 μg/kg body weight is optimal for inducing acute inflammation in Wuzhishan miniature pigs. These findings highlight the importance of considering both the duration of OS induction and the specific research objectives when establishing OS models. Full article
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12 pages, 811 KiB  
Article
Kynurenic Acid Synthesis from D-Kynurenine in the Cerebellum: A Distinct Role of D-Amino Acid Oxidase
by Verónica Pérez de la Cruz, Korrapati V. Sathyasaikumar, Xiao-Dan Wang, Tonali Blanco Ayala, Sarah Beggiato, Dinora F. González Esquivel, Benjamin Pineda and Robert Schwarcz
Cells 2025, 14(13), 1030; https://doi.org/10.3390/cells14131030 - 5 Jul 2025
Viewed by 535
Abstract
The enzymatic formation of kynurenic acid (KYNA), a neuromodulator metabolite of the kynurenine pathway (KP) of tryptophan metabolism, in the mammalian brain is widely attributed to kynurenine aminotransferase II (KATII). However, an alternative biosynthetic route, involving the conversion of D-kynurenine (D-KYN) to KYNA [...] Read more.
The enzymatic formation of kynurenic acid (KYNA), a neuromodulator metabolite of the kynurenine pathway (KP) of tryptophan metabolism, in the mammalian brain is widely attributed to kynurenine aminotransferase II (KATII). However, an alternative biosynthetic route, involving the conversion of D-kynurenine (D-KYN) to KYNA by D-amino acid oxidase (D-AAO), may play a role as well. In the present study, we first confirmed that purified D-AAO efficiently converted D-KYN—but not L-KYN—to KYNA. We then examined KYNA formation from D-KYN (100 µM) in vitro, using tissue homogenates from several human brain regions. KYNA was generated in all areas, with D-AAO-specific production being most effective by far in the cerebellum. Next tested in homogenates from rat cerebellum, KYNA neosynthesis was significantly reduced by D-AAO inhibition, whereas KATII inhibition had no effect. Finally, KYNA production was assessed by in vivo microdialysis in rat cerebellum. Local D-KYN perfusion, alone and in combination with inhibitors of D-AAO (kojic acid) or aminotransferases (AOAA), caused a substantive increase in extracellular KYNA levels. This effect was attenuated dose-dependently by micromolar concentrations of kojic acid, whereas co-perfusion of AOAA (1 mM) was ineffective. Together, our findings indicate that D-AAO should be considered a major contributor to KYNA production in the cerebellum, highlighting region-specific qualitative differences in cerebral KYNA metabolism. Full article
(This article belongs to the Section Cell Signaling)
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16 pages, 2414 KiB  
Article
Prolonged In Vivo Chemogenetic Generation of Hydrogen Peroxide by Endothelial Cells Induces Cardiac Remodelling and Vascular Dysfunction
by Melina Lopez, Niklas Herrle, Bardia Amirmiran, Pedro F. Malacarne, Julia Werkhäuser, Souradeep Chatterjee, Carine Kader, Victoria Jurisch, Xin Wen, Maedeh Gheisari, Katrin Schäfer, Christian Münch, Florian Leuschner, Ralf Gilsbach, Flávia Rezende and Ralf P. Brandes
Antioxidants 2025, 14(6), 705; https://doi.org/10.3390/antiox14060705 - 10 Jun 2025
Viewed by 581
Abstract
Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease. ROS impact the function of proteins largely through thiol modification leading to redox signalling. Acute, targeted interference with local ROS levels has been difficult. Therefore, how dynamics in redox signalling [...] Read more.
Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease. ROS impact the function of proteins largely through thiol modification leading to redox signalling. Acute, targeted interference with local ROS levels has been difficult. Therefore, how dynamics in redox signalling impact cardiovascular health is still a matter of current research. An inducible, endothelial cell-specific knock-in mouse model expressing a yeast D-amino acid oxidase enzyme was generated (Hipp11-Flox-Stop-Flox-yDAO-Cdh5-CreERT2+/0 referred to as ecDAO). DAO releases H2O2 as a by-product of the conversion of D-amino acids into imino acids. The D-amino acid treatment of DAO-expressing cells therefore increases their intracellular H2O2 production. The induction of yDAO in the ecDAO mice was performed with tamoxifen. Subsequently, the mice received D-Alanine (D-Ala, 0.5 M) through drinking water, and the effects on ROS production and vascular and cardiac function were determined. ecDAO induction increased endothelial ROS production as well as ROS production in the lung, which is rich in endothelial cells. The functional consequences of this were, however limited: After minimally invasive myocardial infarction, there was no difference in the outcome between the control (CTL) and ecDAO mice. With respect to vascular function, three days of D-Ala slightly improved vascular function as demonstrated by an increase in the diameter of the carotid artery in vivo and decreased vessel constriction to phenylephrine. Fifty-two days of D-Ala induced cardiac remodelling, increased peripheral resistance, and overoxidation of peroxiredoxins. In conclusion, acute stimulation of endothelial ROS improves cardiovascular function, whereas prolonged ROS exposure deteriorates it. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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20 pages, 530 KiB  
Review
Glutamate-Based Therapeutic Strategies for Schizophrenia: Emerging Approaches Beyond Dopamine
by Mihaela Fadgyas-Stanculete and Octavia Oana Capatina
Int. J. Mol. Sci. 2025, 26(9), 4331; https://doi.org/10.3390/ijms26094331 - 2 May 2025
Cited by 1 | Viewed by 1977
Abstract
Schizophrenia is a complex neuropsychiatric disorder composed of primary cluster-positive symptoms, negative symptoms, disorganization, neurocognitive deficits, and social cognitive impairments. While traditional antipsychotics primarily target dopamine pathways, they provide limited efficacy against cognitive deficits and negative symptoms. Growing evidence implicates glutamatergic dysregulation, particularly [...] Read more.
Schizophrenia is a complex neuropsychiatric disorder composed of primary cluster-positive symptoms, negative symptoms, disorganization, neurocognitive deficits, and social cognitive impairments. While traditional antipsychotics primarily target dopamine pathways, they provide limited efficacy against cognitive deficits and negative symptoms. Growing evidence implicates glutamatergic dysregulation, particularly N-methyl-D-aspartate receptor (NMDA-R) hypofunction, in the pathophysiology of schizophrenia, making glutamate modulation a promising therapeutic approach. This review explores emerging glutamate-based treatment strategies, including NMDA receptor modulators, metabotropic glutamate receptor (mGluR) agents, glutamate transporter regulators, and kynurenine pathway inhibitors. We summarize preclinical and clinical findings on NMDA co-agonists (D-serine and glycine), glycine transporter inhibitors, D-amino acid oxidase inhibitors, and mGluR-targeted therapies, highlighting their mechanisms, efficacy, and limitations. In addition, we discuss novel interventions aimed at restoring glutamate homeostasis, including neuroinflammatory modulation and synaptic plasticity enhancers. Despite promising results, many glutamate-targeting therapies have yielded inconsistent clinical outcomes, underscoring the need for biomarker-driven patient selection and optimized treatment protocols. We propose that integrating glutamate modulators with existing antipsychotic regimens may enhance therapeutic response while minimizing side effects. Future research should focus on refining glutamate-based interventions, identifying predictive biomarkers, and addressing the heterogeneity in schizophrenia pathology. With continued advancements, glutamate modulation has the potential to transform schizophrenia treatment, particularly for cognitive and negative symptoms that remain largely unaddressed by current therapies. Full article
(This article belongs to the Special Issue Novel Therapies for Schizophrenia: Beyond Dopamine)
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16 pages, 270 KiB  
Article
Effects of Dietary Copper Sources and Levels on Liver Copper Metabolism and the Expression of Transporters in Growing Pigs
by Rui Sun, Meng Li, Tianrui Zhang, Wenyan Yang and Lianyu Yang
Animals 2025, 15(4), 526; https://doi.org/10.3390/ani15040526 - 12 Feb 2025
Viewed by 963
Abstract
Research on the effects of organic and inorganic Cu sources on metabolic processes and mechanisms in pigs is lacking. This study investigated the effects of different copper (Cu) sources and levels on hepatic Cu metabolism and transporter factors in growing pigs. Sixty healthy [...] Read more.
Research on the effects of organic and inorganic Cu sources on metabolic processes and mechanisms in pigs is lacking. This study investigated the effects of different copper (Cu) sources and levels on hepatic Cu metabolism and transporter factors in growing pigs. Sixty healthy piglets (initial body weight 14.00 ± 0.30 kg) were randomly divided into four groups with five replicates of three pigs each. Four diets (AM, AH, BM, and BH) had different Cu sources [Cu sulphate (CuSO4): A and Cu amino acids (Cu-AA): B] and levels [supplemented (120 mg/kg DM): M, supplemented (240 mg/kg DM): H]. The pre-feeding period was 7 days, followed by a 45-day feeding period. Slaughter and sample collection were carried out on the 46th day of the formal feeding period. Significant differences were considered at p < 0.05. The final weight and average daily gain (ADG) of growing pigs in the Cu-AA groups were significantly higher than those in the CuSO4 groups. Serum Cu increased with increasing Cu supplementation on days 20 and 40. Cu concentrations in muscle, liver, and liver subcellular organelles were higher in Cu-AA groups. In the CuSO4 groups, Cu concentrations were higher in kidneys and faeces. In Cu-AA groups, both the Cu concentrations in lysosomes and cytosol were higher, and the activities of cathepsin D (CTSD), β-glucosidase (BGL), and acid phosphatase (ACP) in lysosomes and cytoplasm were higher. Comparisons between groups showed that liver mRNA of copper transporter protein 1 (CTR1), ATPase copper-transporting beta (ATP7B), ceruloplasmin (CP), antioxidant protein 1 (ATOX1), and metallothionein (MT) was lower in the CuSO4 group than in the Cu-AA group, with the best performance at 120 mg/kg Cu. mRNAs for ATPase copper-transporting alpha (ATP7A), cytochrome c oxidase copper chaperone 17 (COX17), and copper chaperone for superoxide dismutase (CCS) showed a decreasing trend in the Cu-AA groups. Cu-AA is better for Cu deposition, enhances the utilisation of Cu, reduces Cu excretion, and promotes the expression of relevant enzymes and transporters in the liver. Full article
(This article belongs to the Special Issue Exploration of Sustainable Feed Resources and Pig Dietary Strategies)
23 pages, 3793 KiB  
Article
Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of Crotalus durissus ruruima Venom and Antivenom Efficacy
by Poliana J. Demico, Isabele N. Oliveira, Vitória S. Proença-Hirata, Samuel R. Dias, Hugo A. Ghirotti, Elisangela O. Silva, Inês C. Giometti, Francis L. Pacagnelli, Kristian A. Torres-Bonilla, Stephen Hyslop, Nathália C. Galizio, Karen de Morais-Zani, Manuela B. Pucca, Anderson M. Rocha, Jéssica B. Maciel, Marco A. Sartim, Wuelton M. Monteiro and Rafael S. Floriano
Pharmaceuticals 2025, 18(1), 54; https://doi.org/10.3390/ph18010054 - 6 Jan 2025
Cited by 1 | Viewed by 3328
Abstract
Background: We compared the enzymatic, coagulant, and neuromuscular activities of two variants (yellow—CDRy and white—CDRw) of Crotalus durissus ruruima venom with a sample of C. d. terrificus (CDT) venom and examined their neutralization by antivenom against CDT venom. Methods: The venoms were screened [...] Read more.
Background: We compared the enzymatic, coagulant, and neuromuscular activities of two variants (yellow—CDRy and white—CDRw) of Crotalus durissus ruruima venom with a sample of C. d. terrificus (CDT) venom and examined their neutralization by antivenom against CDT venom. Methods: The venoms were screened for enzymatic and coagulant activities using standard assays, and electrophoretic profiles were compared by SDS-PAGE. Neutralization was assessed by preincubating venoms with crotalic antivenom and assaying the residual activity. Results: SDS-PAGE showed that the venoms had similar electrophoretic profiles, with the main bands being phospholipase A2 (PLA2), serine proteinases, L-amino acid oxidase (LAAO), and phosphodiesterase. CDRy venom had the highest proteolytic and LAAO activities, CDRw venom had greater PLA2 and esterolytic activities at the highest quantity tested, and CDT had greater PLA2 activity than CDRy. CDRw and CDT venoms had similar proteolytic and LAAO activities, and CDRy and CDT venoms had comparable esterolytic activity. None of the venoms altered the prothrombin time (PT), but all of them decreased the activated partial thromboplastin time (aPPT); this activity was neutralized by antivenom. The minimum coagulant dose potency was CDRw >> CDRy > CDT. All venoms had thrombin-like activity that was attenuated by antivenom. CDRy and CDRw venoms showed α-fibrinogenolytic activity. All venoms partially cleaved the β-chain. CDRy and CDT venoms caused neuromuscular facilitation (enhanced muscle contractions) followed by complete blockade, whereas CDRw venom caused only blockade. Antivenom neutralized the neuromuscular activity to varying degrees. Conclusions: These findings indicate that while CDR and CDT venoms share similarities, they also differ in some enzymatic and biological activities and in neutralization by antivenom. Some of these differences could influence the clinical manifestations of envenomation by C. d. ruruima and their neutralization by the currently used therapeutic antivenom. Full article
(This article belongs to the Special Issue Neuromuscular Disorders: Current Gene and Cell Therapeutic Approaches)
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12 pages, 1833 KiB  
Article
Antihypertensive Effects of a Sodium Thiosulfate-Loaded Nanoparticle in a Juvenile Chronic Kidney Disease Rat Model
by You-Lin Tain, Chien-Ning Hsu, Chih-Yao Hou and Chih-Kuang Chen
Antioxidants 2024, 13(12), 1574; https://doi.org/10.3390/antiox13121574 - 20 Dec 2024
Cited by 1 | Viewed by 1082
Abstract
Sodium thiosulfate (STS), a precursor of hydrogen sulfide (H2S), has demonstrated antihypertensive properties. Previous studies have suggested that H2S-based interventions can prevent hypertension in pediatric chronic kidney disease (CKD). However, the clinical application of STS is limited by its [...] Read more.
Sodium thiosulfate (STS), a precursor of hydrogen sulfide (H2S), has demonstrated antihypertensive properties. Previous studies have suggested that H2S-based interventions can prevent hypertension in pediatric chronic kidney disease (CKD). However, the clinical application of STS is limited by its rapid release and intravenous administration. To address this, we developed a poly-lactic acid (PLA)-based nanoparticle system for sustained STS delivery and investigated whether weekly treatment with STS-loaded nanoparticles (NPs) could protect against hypertension in a juvenile CKD rat model. Male Sprague Dawley rats, aged three weeks, were fed a diet containing 0.5% adenine for three weeks to induce a model of pediatric CKD. STS-loaded NPs (25 mg/kg) were administered intravenously during weeks 6, 7, and 8, and at week 9, all rats were sacrificed. Treatment with STS-loaded NPs reduced systolic and diastolic blood pressure by 10 mm Hg and 8 mm Hg, respectively, in juvenile CKD rats. The protective effect of STS-loaded NPs was linked to increased renal expression of H2S-producing enzymes, including cystathionine γ-lyase (CSE) and D-amino acid oxidase (DAO). Additionally, STS-loaded NP therapy restored nitric oxide (NO) signaling, increasing L-arginine levels, which were disrupted in CKD. Furthermore, the beneficial effects of STS-loaded NPs were associated with inhibition of the renin–angiotensin system (RAS) and the enhancement of the NO signaling pathway. Our findings suggest that STS-loaded NP treatment provides sustained STS delivery and effectively reduces hypertension in a juvenile CKD rat model, bringing us closer to the clinical translation of STS-based therapy for pediatric CKD-induced hypertension. Full article
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20 pages, 5940 KiB  
Article
Endemic Radiation of African Moonfish, Selene dorsalis (Gill 1863), in the Eastern Atlantic: Mitogenomic Characterization and Phylogenetic Implications of Carangids (Teleostei: Carangiformes)
by Emmanuel Ofosu Mireku Ewusi, Soo Rin Lee, Ah Ran Kim, Yunji Go, Hsu Htoo, Sangdeok Chung, Muhammad Hilman Fu’adil Amin, Sapto Andriyono, Hyun-Woo Kim and Shantanu Kundu
Biomolecules 2024, 14(10), 1208; https://doi.org/10.3390/biom14101208 - 25 Sep 2024
Cited by 1 | Viewed by 1764
Abstract
This study offers an in-depth analysis of the mitochondrial genome of Selene dorsalis (Gill 1863), a species native to the Eastern Atlantic Ocean. The circular mitochondrial DNA molecule measures 16,541 base pairs and comprises 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, [...] Read more.
This study offers an in-depth analysis of the mitochondrial genome of Selene dorsalis (Gill 1863), a species native to the Eastern Atlantic Ocean. The circular mitochondrial DNA molecule measures 16,541 base pairs and comprises 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA genes, and a control region (CR). The nucleotide composition exhibits a notable adenine-thymine (AT) bias, accounting for 53.13%, which aligns with other species in the Carangidae family. Most PCGs initiate with the ATG codon, with the exception of Cytochrome C oxidase subunit I, which starts with GTG. Analysis of relative synonymous codon usage reveals that leucine and serine are the most prevalent amino acids in the mitochondrial genome of S. dorsalis and its congeners (S. vomer and S. setapinnis). All tRNAs display the typical cloverleaf structure, though tRNA Serine (S1) lacks a dihydrouracil arm. Pairwise comparisons of synonymous and nonsynonymous substitutions for all PCGs yielded values below ‘1’, indicating strong purifying selection. The CR spans 847 bp, representing 5.12% of the mitochondrial genome, and is characterized by high AT content (62.81%). It is situated between tRNA-Pro (TGG) and tRNA-Phe (GAA). The CR contains conserved sequence blocks, with CSB-1 being the longest at 22 bp and CSB-D the shortest at 18 bp. Phylogenetic analysis, using Bayesian and Maximum-likelihood trees constructed from concatenated PCGs across 72 species, successfully differentiates S. dorsalis from other carangids. This study also explores how ocean currents and gyres might influence lineage diversification and parapatric speciation of Selene species between the Atlantic and Pacific Oceans. These results highlight the importance of the mitochondrial genome in elucidating the structural organization and evolutionary dynamics of S. dorsalis and its relatives within marine ecosystems. Full article
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23 pages, 7409 KiB  
Article
Computational Screening of T-Muurolol for an Alternative Antibacterial Solution against Staphylococcus aureus Infections: An In Silico Approach for Phytochemical-Based Drug Discovery
by Soham Bhattacharya, Pijush Kanti Khanra, Adrish Dutta, Neha Gupta, Zahra Aliakbar Tehrani, Lucie Severová, Karel Šrédl, Marek Dvořák and Eloy Fernández-Cusimamani
Int. J. Mol. Sci. 2024, 25(17), 9650; https://doi.org/10.3390/ijms25179650 - 6 Sep 2024
Cited by 7 | Viewed by 1970
Abstract
Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in [...] Read more.
Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in this study, we have screened T-muurolol for possible interactions with several S. aureus-specific bacterial proteins to establish its potential as an alternative antibacterial agent. Based on its binding affinity and interactions with amino acids, T-muurolol was identified as a potential inhibitor of S. aureus lipase, dihydrofolate reductase, penicillin-binding protein 2a, D-Ala:D-Ala ligase, and ribosome protection proteins tetracycline resistance determinant (RPP TetM), which indicates its potentiality against S. aureus and its multi-drug-resistant strains. Also, T-muurolol exhibited good antioxidant and anti-inflammatory activity by showing strong binding interactions with flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, and cyclooxygenase-2. Consequently, molecular dynamics (MD) simulation and recalculating binding free energies elucidated its binding interaction stability with targeted proteins. Furthermore, quantum chemical structure analysis based on density functional theory (DFT) depicted a higher energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (EHOMO-LUMO) with a lower chemical potential index, and moderate electrophilicity suggests its chemical hardness and stability and less polarizability and reactivity. Additionally, pharmacological parameters based on ADMET, Lipinski’s rules, and bioactivity score validated it as a promising drug candidate with high activity toward ion channel modulators, nuclear receptor ligands, and enzyme inhibitors. In conclusion, the current findings suggest T-muurolol as a promising alternative antibacterial agent that might be a potential phytochemical-based drug against S. aureus. This study also suggests further clinical research before human application. Full article
(This article belongs to the Special Issue Recent Advances in Medicinal Plants and Natural Products)
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13 pages, 1250 KiB  
Article
Aquibium pacificus sp. nov., a Novel Mixotrophic Bacterium from Bathypelagic Seawater in the Western Pacific Ocean
by Fan Jiang, Xun Hao, Ding Li, Xuying Zhu, Jiamei Huang, Qiliang Lai, Jianning Wang, Liping Wang and Zongze Shao
Microorganisms 2024, 12(8), 1584; https://doi.org/10.3390/microorganisms12081584 - 4 Aug 2024
Cited by 2 | Viewed by 1232
Abstract
A novel Gram-stain-negative, facultatively anaerobic, and mixotrophic bacterium, designated as strain LZ166T, was isolated from the bathypelagic seawater in the western Pacific Ocean. The cells were short rod-shaped, oxidase- and catalase-positive, and motile by means of lateral flagella. The growth of [...] Read more.
A novel Gram-stain-negative, facultatively anaerobic, and mixotrophic bacterium, designated as strain LZ166T, was isolated from the bathypelagic seawater in the western Pacific Ocean. The cells were short rod-shaped, oxidase- and catalase-positive, and motile by means of lateral flagella. The growth of strain LZ166T was observed at 10–45 °C (optimum 34–37 °C), at pH 5–10 (optimum 6–8), and in the presence of 0–5% NaCl (optimum 1–3%). A phylogenetic analysis based on the 16S rRNA gene showed that strain LZ166T shared the highest similarity (98.58%) with Aquibium oceanicum B7T and formed a distinct branch within the Aquibium genus. The genomic characterization, including average nucleotide identity (ANI, 90.73–76.79%), average amino identity (AAI, 88.50–79.03%), and digital DNA–DNA hybridization (dDDH, 36.1–22.2%) values between LZ166T and other species within the Aquibium genus, further substantiated its novelty. The genome of strain LZ166T was 6,119,659 bp in size with a 64.7 mol% DNA G+C content. The predominant fatty acid was summed feature 8 (C18:1ω7c and/or C18:1ω6c). The major polar lipids identified were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), glycolipid (GL), and phosphatidylglycerol (PG), with ubiquinone-10 (Q-10) as the predominant respiratory quinone. The genomic annotation indicated the presence of genes for a diverse metabolic profile, including pathways for carbon fixation via the Calvin–Benson–Bassham cycle and inorganic sulfur oxidation. Based on the polyphasic taxonomic results, strain LZ166T represented a novel species of the genus Aquibium, for which the name Aquibium pacificus sp. nov. is proposed, with the type strain LZ166T (=MCCC M28807T = KACC 23148T = KCTC 82889T). Full article
(This article belongs to the Section Microbiomes)
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25 pages, 4204 KiB  
Article
Chemokine Receptor Antagonists Prevent and Reverse Cofilin-Actin Rod Pathology and Protect Synapses in Cultured Rodent and Human iPSC-Derived Neurons
by Thomas B. Kuhn, Laurie S. Minamide, Lubna H. Tahtamouni, Sydney A. Alderfer, Keifer P. Walsh, Alisa E. Shaw, Omar Yanouri, Henry J. Haigler, Michael R. Ruff and James R. Bamburg
Biomedicines 2024, 12(1), 93; https://doi.org/10.3390/biomedicines12010093 - 1 Jan 2024
Cited by 2 | Viewed by 4209
Abstract
Synapse loss is the principal cause of cognitive decline in Alzheimer’s disease (AD) and related disorders (ADRD). Synapse development depends on the intricate dynamics of the neuronal cytoskeleton. Cofilin, the major protein regulating actin dynamics, can be sequestered into cofilactin rods, intra-neurite bundles [...] Read more.
Synapse loss is the principal cause of cognitive decline in Alzheimer’s disease (AD) and related disorders (ADRD). Synapse development depends on the intricate dynamics of the neuronal cytoskeleton. Cofilin, the major protein regulating actin dynamics, can be sequestered into cofilactin rods, intra-neurite bundles of cofilin-saturated actin filaments that can disrupt vesicular trafficking and cause synaptic loss. Rods are a brain pathology in human AD and mouse models of AD and ADRD. Eliminating rods is the focus of this paper. One pathway for rod formation is triggered in ~20% of rodent hippocampal neurons by disease-related factors (e.g., soluble oligomers of Amyloid-β (Aβ)) and requires cellular prion protein (PrPC), active NADPH oxidase (NOX), and cytokine/chemokine receptors (CCRs). FDA-approved antagonists of CXCR4 and CCR5 inhibit Aβ-induced rods in both rodent and human neurons with effective concentrations for 50% rod reduction (EC50) of 1–10 nM. Remarkably, two D-amino acid receptor-active peptides (RAP-103 and RAP-310) inhibit Aβ-induced rods with an EC50 of ~1 pM in mouse neurons and ~0.1 pM in human neurons. These peptides are analogs of D-Ala-Peptide T-Amide (DAPTA) and share a pentapeptide sequence (TTNYT) antagonistic to several CCR-dependent responses. RAP-103 does not inhibit neuritogenesis or outgrowth even at 1 µM, >106-fold above its EC50. N-terminal methylation, or D-Thr to D-Ser substitution, decreases the rod-inhibiting potency of RAP-103 by 103-fold, suggesting high target specificity. Neither RAP peptide inhibits neuronal rod formation induced by excitotoxic glutamate, but both inhibit rods induced in human neurons by several PrPC/NOX pathway activators (Aβ, HIV-gp120 protein, and IL-6). Significantly, RAP-103 completely protects against Aβ-induced loss of mature and developing synapses and, at 0.1 nM, reverses rods in both rodent and human neurons (T½ ~ 3 h) even in the continuous presence of Aβ. Thus, this orally available, brain-permeable peptide should be highly effective in reducing rod pathology in multifactorial neurological diseases with mixed proteinopathies acting through PrPC/NOX. Full article
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16 pages, 9579 KiB  
Article
Metabolic Pathway Engineering Improves Dendrobine Production in Dendrobium catenatum
by Meili Zhao, Yanchang Zhao, Zhenyu Yang, Feng Ming, Jian Li, Demin Kong, Yu Wang, Peng Chen, Meina Wang and Zhicai Wang
Int. J. Mol. Sci. 2024, 25(1), 397; https://doi.org/10.3390/ijms25010397 - 28 Dec 2023
Cited by 10 | Viewed by 2449
Abstract
The sesquiterpene alkaloid dendrobine, widely recognized as the main active compound and a quality control standard of medicinal orchids in the Chinese Pharmacopoeia, demonstrates diverse biological functions. In this study, we engineered Dendrobium catenatum as a chassis plant for the production of dendrobine [...] Read more.
The sesquiterpene alkaloid dendrobine, widely recognized as the main active compound and a quality control standard of medicinal orchids in the Chinese Pharmacopoeia, demonstrates diverse biological functions. In this study, we engineered Dendrobium catenatum as a chassis plant for the production of dendrobine through the screening and pyramiding of key biosynthesis genes. Initially, previously predicted upstream key genes in the methyl-D-erythritol 4-phosphate (MEP) pathway for dendrobine synthesis, including 4-(Cytidine 5′-Diphospho)-2-C-Methyl-d-Erythritol Kinase (CMK), 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase (DXR), 2-C-Methyl-d-Erythritol 4-Phosphate Cytidylyltransferase (MCT), and Strictosidine Synthase 1 (STR1), and a few downstream post-modification genes, including Cytochrome P450 94C1 (CYP94C1), Branched-Chain-Amino-Acid Aminotransferase 2 (BCAT2), and Methyltransferase-like Protein 23 (METTL23), were chosen due to their deduced roles in enhancing dendrobine production. The seven genes (SG) were then stacked and transiently expressed in the leaves of D. catenatum, resulting in a dendrobine yield that was two-fold higher compared to that of the empty vector control (EV). Further, RNA-seq analysis identified Copper Methylamine Oxidase (CMEAO) as a strong candidate with predicted functions in the post-modification processes of alkaloid biosynthesis. Overexpression of CMEAO increased dendrobine content by two-fold. Additionally, co-expression analysis of the differentially expressed genes (DEGs) by weighted gene co-expression network analysis (WGCNA) retrieved one regulatory transcription factor gene MYB61. Overexpression of MYB61 increased dendrobine levels by more than two-fold in D. catenatum. In short, this work provides an efficient strategy and prospective candidates for the genetic engineering of D. catenatum to produce dendrobine, thereby improving its medicinal value. Full article
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20 pages, 4626 KiB  
Article
Genome-Wide Identification, Characterization, and Expression Analysis of the Copper-Containing Amine Oxidase Gene Family in Mangrove Kandelia obovata
by Quaid Hussain, Ting Ye, Chenjing Shang, Sihui Li, Jackson Nkoh Nkoh, Wenyi Li and Zhangli Hu
Int. J. Mol. Sci. 2023, 24(24), 17312; https://doi.org/10.3390/ijms242417312 - 9 Dec 2023
Cited by 3 | Viewed by 2734
Abstract
Copper-containing amine oxidases (CuAOs) are known to have significant involvement in the process of polyamine catabolism, as well as serving crucial functions in plant development and response to abiotic stress. A genome-wide investigation of the CuAO protein family was previously carried [...] Read more.
Copper-containing amine oxidases (CuAOs) are known to have significant involvement in the process of polyamine catabolism, as well as serving crucial functions in plant development and response to abiotic stress. A genome-wide investigation of the CuAO protein family was previously carried out in sweet orange (Citrus sinensis) and sweet cherry (Prunus avium L.). Six CuAO (KoCuAO1-KoCuAO6) genes were discovered for the first time in the Kandelia obovata (Ko) genome through a genome-wide analysis conducted to better understand the key roles of the CuAO gene family in Kandelia obovata. This study encompassed an investigation into various aspects of gene analysis, including gene characterization and identification, subcellular localization, chromosomal distributions, phylogenetic tree analysis, gene structure analysis, motif analysis, duplication analysis, cis-regulatory element identification, domain and 3D structural variation analysis, as well as expression profiling in leaves under five different treatments of copper (CuCl2). Phylogenetic analysis suggests that these KoCuAOs, like sweet cherry, may be subdivided into three subgroups. Examining the chromosomal location revealed an unequal distribution of the KoCuAO genes across four out of the 18 chromosomes in Kandelia obovata. Six KoCuAO genes have coding regions with 106 and 159 amino acids and exons with 4 and 12 amino acids. Additionally, we discovered that the 2.5 kb upstream promoter region of the KoCuAOs predicted many cis elements linked to phytohormones and stress responses. According to the expression investigations, CuCl2 treatments caused up- and downregulation of all six genes. In conclusion, our work provides a comprehensive overview of the expression pattern and functional variety of the Kandelia obovata CuAO gene family, which will facilitate future functional characterization of each KoCuAO gene. Full article
(This article belongs to the Special Issue Advances in Forest Tree Physiology, Breeding and Genetic Research)
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45 pages, 19670 KiB  
Review
Chemistry of Hydrogen Sulfide—Pathological and Physiological Functions in Mammalian Cells
by Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Celia Andrés Juan, Francisco J. Plou and Eduardo Pérez-Lebeña
Cells 2023, 12(23), 2684; https://doi.org/10.3390/cells12232684 - 22 Nov 2023
Cited by 30 | Viewed by 4589
Abstract
Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of hydrogen sulfide (H2S) in the human [...] Read more.
Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. This article provides an overview of the physiological significance of H2S in the human body. It highlights the various sources of H2S production in different situations and examines existing techniques for detecting this gas. Full article
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14 pages, 3982 KiB  
Article
Cysteine Attenuates the Impact of Bisphenol A-Induced Oxidative Damage on Growth Performance and Intestinal Function in Piglets
by Pengxiang Qin, Shangyuan Ma, Changjin Li, Yanjiao Di, Zihao Liu, Huiru Wang, Yang Li, Shuzhen Jiang, Weiren Yang and Ning Jiao
Toxics 2023, 11(11), 902; https://doi.org/10.3390/toxics11110902 - 3 Nov 2023
Cited by 5 | Viewed by 1590
Abstract
Bisphenol A (BPA), a kind of environmental toxin, widely impacts daily life. Cysteine (Cys) is a nutritionally important amino acid for piglets. However, it remains unclear whether Cys can alleviate BPA-induced oxidative damage in piglets. The aim of the present study was to [...] Read more.
Bisphenol A (BPA), a kind of environmental toxin, widely impacts daily life. Cysteine (Cys) is a nutritionally important amino acid for piglets. However, it remains unclear whether Cys can alleviate BPA-induced oxidative damage in piglets. The aim of the present study was to explore the protective effects of Cys in BPA-challenged piglets. A total of twenty-four piglets were divided into four groups that were further subdivided based on the type of exposure (with or without 0.1% BPA) in a basal or Cys diet for a 28 d feeding trial. The results showed that BPA exposure decreased the piglets’ average daily weight gain by 14.9%, and decreased dry matter, crude protein and ether extract digestibility by 3.3%, 4.5% and 2.3%, respectively; these decreases were attenuated by Cys supplementation. Additionally, Cys supplementation restored BPA-induced decreases in superoxide dismutase (SOD) and glutathione (GSH), and increases in malondialdehyde (MDA) levels, in the serum and jejunum (p < 0.05). Moreover, BPA decreased the jejunal mRNA expression of antioxidant genes, which were restored by Cys supplementation (p < 0.05). Cys also restored BPA and increased serum D-lactate levels and diamine oxidase (DAO) activity, and BPA decreased jejunal disaccharidase activity (p < 0.05). Further investigations in this study showed that the protective effects of Cys were associated with restoring intestinal barrier integrity by improving the jejunal morphology and enhancing the mRNA expression of tight junction proteins (p < 0.05). Collectively, the results herein demonstrated that Cys supplementation attenuated the impact of BPA-induced oxidative damage on growth performance, nutrient digestibility and intestinal function. Full article
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