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Keywords = d-amino acid oxidase

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12 pages, 4257 KB  
Article
Parasedimentitalea nitratireducens sp. nov., a Novel Nitrate-Reducing Bacterium Isolated from the Yellow Sea
by Yanjiao Zhang, Xinyu Liu, Hao Yu and Xiuqing Yang
Microorganisms 2026, 14(8), 1706; https://doi.org/10.3390/microorganisms14081706 - 4 Aug 2026
Viewed by 349
Abstract
A Gram-stain-negative, rod-shaped, aerobic strain CY06T was isolated from surface marine sediment sample of the Yellow Sea, China. The strain was positive for oxidase and catalase and could reduce nitrate to nitrite but not further to gaseous nitrogen products. Phylogenetic analysis based [...] Read more.
A Gram-stain-negative, rod-shaped, aerobic strain CY06T was isolated from surface marine sediment sample of the Yellow Sea, China. The strain was positive for oxidase and catalase and could reduce nitrate to nitrite but not further to gaseous nitrogen products. Phylogenetic analysis based on 16S rRNA gene sequences and the up-to-date bacterial core gene (UBCG) sequences revealed that strain CY06T formed a distinct clade within the genus Parasedimentitalea. Genomic comparisons, including digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI) and average amino acid identity (AAI), clearly distinguished strain CY06T from other members of the genus. The morphological, physiological, biochemical and chemotaxonomic data further supported its differentiation from closely related species. Based on the polyphasic evidence, a new species, Parasedimentitalea nitratireducens sp. nov., is proposed, with the type strain CY06T (=MCCC 1K08636T = KCTC 72006T). Full article
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21 pages, 12162 KB  
Article
Metagenomic and Metabolomic Insights into Volatile Flavor Changes and Microbial Community Shifts in Physalis pubescens L. Fermentation by Lactiplantibacillus plantarum
by Song Yan, Jialei Li, Kaixin Chen, Chuanying Ren, Shan Zhang, Qing Chen, Yang Gao and Bin Liu
Molecules 2026, 31(13), 2377; https://doi.org/10.3390/molecules31132377 - 6 Jul 2026
Viewed by 463
Abstract
Physalis pubescens L. is a seasonal fruit with high nutritional value but a short shelf life that limits its processing and utilization. This study integrated metagenomics and metabolomics to investigate the comparative effects of Lactiplantibacillus plantarum fermentation on volatile flavor metabolites and microbial [...] Read more.
Physalis pubescens L. is a seasonal fruit with high nutritional value but a short shelf life that limits its processing and utilization. This study integrated metagenomics and metabolomics to investigate the comparative effects of Lactiplantibacillus plantarum fermentation on volatile flavor metabolites and microbial community composition of P. pubescens by comparing initial (0 h) and post-fermentation (24 h) states. After 24 h of fermentation, 1316 volatile compounds were putatively identified by GC-MS, with 592 metabolites significantly changed and 501 upregulated and 91 downregulated. Key flavor compounds that impart citrus, floral, fruity, and rose notes including D-limonene, geraniol, D-carvone, and phenylethyl alcohol were markedly increased. Metagenomic analysis revealed that L. plantarum rapidly dominated the microbial community (relative abundance surged from <0.05% to ~72%) while effectively suppressing potential spoilage bacteria such as Escherichia coli. Functional gene annotation demonstrated significant enrichment of amino acid, carbohydrate, and fatty acid metabolism pathways, with key enzyme genes (L-lactate dehydrogenase, pyruvate oxidase, acetyl-CoA carboxylase) predominantly assigned to L. plantarum, suggesting their potential contribution to the generation of organic acids, ethanol, and esters. Spearman correlation analysis indicated that Lactobacillaceae genera were significantly positively correlated with terpenoids, phenols, alcohols, and aldehydes. This study provides the first metagenomics-metabolomics insight into the microbial and molecular mechanisms associated with flavor formation in LAB-fermented P. pubescens, offering a theoretical foundation for developing stable and controllable fermented fruit products. Full article
(This article belongs to the Special Issue Advances in Food Analytical Methods)
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23 pages, 2170 KB  
Article
Complete Mitochondrial Genome of Haemulon plumierii (Lacepède, 1801) Supports Its Use as a Sentinel Reef Fish
by Mayra Alejandra Cañizares-Martínez, Jesús Alejandro Zamora-Briseño, Rafael F. Rivera-Bustamante and Rossanna Rodríguez-Canul
Genes 2026, 17(5), 585; https://doi.org/10.3390/genes17050585 - 20 May 2026
Viewed by 789
Abstract
Background: Mitochondrial genomes provide valuable information on evolutionary relationships among organisms and on the selective pressures acting on energy metabolism, increasing their relevance in ecological and environmental genomics studies. Haemulon plumierii is a reef-associated fish distributed throughout the Gulf of Mexico and [...] Read more.
Background: Mitochondrial genomes provide valuable information on evolutionary relationships among organisms and on the selective pressures acting on energy metabolism, increasing their relevance in ecological and environmental genomics studies. Haemulon plumierii is a reef-associated fish distributed throughout the Gulf of Mexico and Caribbean Sea and has been proposed as a bioindicator species within the Mesoamerican Reef System. Methods: In this study, we present a high-quality mitochondrial genome of H. plumierii from the southeastern coast of Mexico generated using PacBio HiFi long-read sequencing. Results: The circular mitogenome is 16,823 bp long and contains the complete set of 37 canonical mitochondrial genes, including 13 protein-coding genes, 22 tRNAs, two rRNAs, and one control region (D-loop). The gene order, strand orientation, and tRNA secondary structures were consistent with the conserved vertebrate mitochondrial architecture. Comparative analyses with closely related haemulid species revealed conserved nucleotide composition patterns, negative GC skew values, strong AT enrichment within the D-loop, and highly conserved mitochondrial synteny. Phylogenetic reconstruction based on complete mitochondrial genomes placed H. plumierii firmly within the Haemulon clade. Selective pressure analyses revealed pervasive purifying selection acting on mitochondrial protein-coding genes, supported by low dN/dS ratios, high amino acid identity, constrained nucleotide diversity in cytochrome oxidase genes, and conserved codon usage patterns shaped primarily by AT-driven mutational bias. Pairwise genetic distance analyses further supported moderate interspecific divergence within Caribbean Haemulon species. Conclusions: Overall, the mitogenomic resource generated here provides an important evolutionary and functional framework for future phylogenetic, ecological, and environmental genomics studies in Caribbean reef fishes. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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21 pages, 1112 KB  
Article
Assessment of the Impacts of Common Morel (Morchella sextelata) Cultivation on Soil Physicochemical Properties and Microbial Communities in Different Environments
by Zhongyan Tang, Chen Chen, Li Dong, Liuyuan Bao, Chengcui Yang, Xiaodan Wang, Xiaoling Chen, Xiaokun Li, Fajun Xiang and Shunqiang Yang
Microorganisms 2026, 14(5), 1115; https://doi.org/10.3390/microorganisms14051115 - 14 May 2026
Viewed by 456
Abstract
Morchella sextelata a species of high nutritional and economic value, is widely cultivated. To investigate how different cultivation environments affect the soil physicochemical properties and microbial communities associated with common morel, this study established cultivation plots under three distinct settings: apple orchard canopies, [...] Read more.
Morchella sextelata a species of high nutritional and economic value, is widely cultivated. To investigate how different cultivation environments affect the soil physicochemical properties and microbial communities associated with common morel, this study established cultivation plots under three distinct settings: apple orchard canopies, dry upland fields, and paddy fields. The objective was to compare the differential impacts of common morel cultivation on soil environmental conditions across these habitats. The results indicate that cultivating common morel effectively enhances soil fertility. Across all environments, soil hydrolyzable nitrogen (HN), available potassium (AK), and organic matter content were higher than in the control. In apple orchard and dryland soils, total phosphorus (TP), total potassium (TK), available phosphorus (AP), and pH values were also elevated compared to the control, with most differences reaching significant levels. Solid Sucrase (S-SC) activity increased in all environments compared to the control, with values of 17.52 mg/d/g in PG, 17.39 mg/d/g in HD, and 21.68 mg/d/g in DT soils. Soil Amylase (S-AL) activity was higher in PG (451.28 μg/h/g) and HD (475.38 μg/h/g) soils. In contrast, Soil-acid phosphatase (S-ACP) activity was significantly elevated in DT soil (2922.08 nmol/h/g). PG soil exhibited significantly higher activities of Solid-Catalase (S-CAT), Solid polyphenol oxidase (S-PPO), and Solid Urease (S-UE), with S-CAT reaching 952.5 μmol/h/g. Following common morel cultivation, bacterial richness and diversity decreased across all conditions, while fungal richness increased but diversity declined. At the phylum level, Proteobacteria remained the dominant bacterial group, accounting for 26.78% in PG, 28.27% in HD, and 20.05% in DT soils. Ascomycota was the predominant fungal phylum, comprising 68.03% in PG, 72.16% in HD, and 68.94% in DT soils. Predicted bacterial functional pathways were primarily associated with metabolism, genetic information processing, environmental information processing, and cellular processes. Key metabolic pathways included carbohydrate metabolism, amino acid metabolism, and metabolism of cofactors and vitamins. fungal functional guilds were mainly classified as pathotrophic, pathotrophic–saprotrophic, pathotrophic–saprotrophic–symbiotrophic, and saprotrophic. Among these, saprotrophic and pathotrophic guilds showed higher abundance compared to the control. This shift is characterized by a reduction in both the diversity and abundance of beneficial microorganisms, alongside an increase in the richness of harmful microbial taxa. The combined effect of these factors disrupts the soil microbial equilibrium. The findings of this study provide a theoretical foundation for the cultivation of common morel and the management of associated soils. Full article
(This article belongs to the Section Environmental Microbiology)
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26 pages, 21033 KB  
Article
Preparation and Characterization of Rice Bran Protein Hydrolysates Enhanced via Alcalase and Lactiplantibacillus plantarum 13110 Co-Treatment: Antioxidant Properties and Ameliorative Effects on Ulcerative Colitis in Mice
by Guanlong Li, Xiaolan Liu, Peng Li, Quanxin Wang, Changyuan Wang and Xiqun Zheng
Nutrients 2026, 18(8), 1278; https://doi.org/10.3390/nu18081278 - 17 Apr 2026
Cited by 1 | Viewed by 766
Abstract
Background: Ulcerative colitis, a chronic inflammatory disorder of the intestine, represents a major health concern worldwide. This study aimed to explore the in vivo efficacy of rice bran protein hydrolysates in mitigating UC. Methods: Rice bran protein hydrolysates with enhanced antioxidant activity were [...] Read more.
Background: Ulcerative colitis, a chronic inflammatory disorder of the intestine, represents a major health concern worldwide. This study aimed to explore the in vivo efficacy of rice bran protein hydrolysates in mitigating UC. Methods: Rice bran protein hydrolysates with enhanced antioxidant activity were prepared via co-treatment with Alcalase and Lactiplantibacillus plantarum 13110. Results: Compared with hydrolysates obtained using Alcalase in isolation (RHP), the co-treated rice bran (CRB) protein hydrolysates exhibited significantly higher antioxidant capacity. Structural characterization revealed marked alterations in molecular weight distribution, amino acid composition, and RHP spectral features, based on Fourier transform infrared spectroscopy, during fermentation with L. plantarum 13110. The 500 mg/kg·bw CRB intervention effectively attenuated oxidative stress and inflammatory responses in dextran sulfate sodium (DSS)-induced colitic mice, as evidenced by significantly reduced colonic levels (p < 0.05) of pro-inflammatory mediators (TNF-α, IL-1β, IL-6, and LPS), decreased serum concentrations of fatty acid-binding protein 2 (FABP2), diamine oxidase (DAO), and D-lactic acid (D-LA), and increased colonic IL-10 content (p < 0.05). These changes were associated with ulcerative colitis amelioration and improved intestinal barrier function. Conclusions: Thus, CRB exhibits promising prophylactic effects against ulcerative colitis, suggesting its potential for therapeutic application. Full article
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40 pages, 3743 KB  
Review
Dietary D-Amino Acids as Context-Dependent Contronymic Molecules in Health and Oxidative Stress
by Hideo Yamasaki, Kakeru B. Mizumoto, Riko F. Naomasa and Michael F. Cohen
Nutraceuticals 2026, 6(1), 15; https://doi.org/10.3390/nutraceuticals6010015 - 3 Mar 2026
Viewed by 2431
Abstract
Recent advances in chiral analytical chemistry have revealed that fermented and natural foods contain substantial amounts of D-amino acids (D-AAs), the mirror-image counterparts of L-amino acids, leading to their recognition as nutraceutical components with potential health relevance. Although clinical evidence provides only limited [...] Read more.
Recent advances in chiral analytical chemistry have revealed that fermented and natural foods contain substantial amounts of D-amino acids (D-AAs), the mirror-image counterparts of L-amino acids, leading to their recognition as nutraceutical components with potential health relevance. Although clinical evidence provides only limited support for their therapeutic efficacy, commercial expectations have outpaced scientific validation, and recent safety concerns emphasize the need for critical evaluation. In this review, we integrate findings from food chemistry, microbiology, biochemistry, physiology, and clinical research to provide a critical overview of dietary D-AAs. We examine how dietary exposure, microbial metabolism, host clearance capacity, and redox status collectively shape their context-dependent biological effects. We highlight the mechanistic linkage between D-amino acid oxidase (DAAO)-mediated hydrogen peroxide (H2O2) generation and organ-specific vulnerability, thereby clarifying the molecular basis of their “double-edged sword” actions. Within this interdisciplinary framework, we propose that D-AAs function as context-dependent “contronymic” molecules in cellular communication. By distinguishing physiological regulation, experimental modulation, and clinical application, this review aims to support evidence-based nutraceutical strategies and safety assessments that harness the potential benefits of D-AAs while minimizing associated risks. Full article
(This article belongs to the Topic Functional Foods and Nutraceuticals in Health and Disease)
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18 pages, 969 KB  
Article
Isolation, Total Synthesis and Anti-Diabetic Activity of Filiforidine from Cassytha filiformis
by Caiyun Zhang, Hong Zhu, Fang Zhang, Yuexia Jiang, Zibao Huang, Dong Lin, Niangen Chen, Xiaopo Zhang and Yanhui Fu
Molecules 2025, 30(24), 4763; https://doi.org/10.3390/molecules30244763 - 12 Dec 2025
Cited by 1 | Viewed by 1040
Abstract
Cassytha filiformis is a folkloric herbal medicine used to treat type 2 diabetes mellitus (T2DM). In this study, an oxidized aporphine alkaloid, designated as Filiforidine (3,10,11-trimethoxy-1,2-methylenedioxy-7-oxoaporphine), was isolated from C. filiformis, and its structure was elucidated through comprehensive spectroscopic analysis. Owing to [...] Read more.
Cassytha filiformis is a folkloric herbal medicine used to treat type 2 diabetes mellitus (T2DM). In this study, an oxidized aporphine alkaloid, designated as Filiforidine (3,10,11-trimethoxy-1,2-methylenedioxy-7-oxoaporphine), was isolated from C. filiformis, and its structure was elucidated through comprehensive spectroscopic analysis. Owing to its novel structure and significant glucose consumption activity, the total synthesis of Filiforidine was achieved for the first time. The key steps featured an electrophilic addition reaction, involving the reduction of a nitro group to an amino group with lithium tetrahydroaluminum, and a copper bromide-catalyzed oxidative aromatization reaction as well as a photocyclization reaction. Several experimental steps were optimized. Furthermore, a complex post-treatment method was developed, which reduced the column chromatography separation steps. Specifically, 2-(4-methoxybenzo[d][1,3]dioxol -5-yl) ethan-1-amine is salted with dilute hydrochloric acid. Cytotoxicity assay and glucose oxidase assay showed that Filiforidine had significant glucose consumption-promoting effects on HL-7702 cells at 0.625 μM, 1.25 μM, and 2.5 μM but without cytotoxicity. Therefore, Filiforidine might be a promising drug candidate for the treatment of diabetes. Full article
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27 pages, 716 KB  
Review
Impact of D-Amino Acids in Schizophrenia
by Serdar M. Dursun, Leman H. Dursun and Glen B. Baker
Biomolecules 2025, 15(9), 1270; https://doi.org/10.3390/biom15091270 - 2 Sep 2025
Cited by 6 | Viewed by 4939
Abstract
Most amino acids contain a chiral center and thus, can exist as L- and D-isomers. For many years, it was thought that only the L-isomers were present in mammals. However, in recent decades it has been demonstrated that D-isomers are also present. Three [...] Read more.
Most amino acids contain a chiral center and thus, can exist as L- and D-isomers. For many years, it was thought that only the L-isomers were present in mammals. However, in recent decades it has been demonstrated that D-isomers are also present. Three of these amino acids, namely D-serine, D-aspartate, and D-alanine, have been proposed to play a role in the etiology of schizophrenia via interactions with glutamate receptors. D-Serine and D-alanine act at the glycine modulatory site on the NMDA receptor, while D-aspartate acts at the glutamate site on the same receptor. D-aspartate also acts on the mGlu5 receptor and can stimulate glutamate release presynaptically. Preclinical studies have reported that manipulations to reduce brain levels of D-serine, D-aspartate, or D-alanine lead to schizophrenia-relevant behaviors, and clinical studies have reported reduced levels of these D-amino acids in the brain tissue (postmortem) and/or body fluids from schizophrenia patients compared to those noted in controls, although there are some contradictory findings. The possible use of these amino acids and/or the manipulation of their relevant enzymes in the treatment of schizophrenia are described. D-Cysteine has been identified recently in human brain tissue, with the highest values in white matter; demonstration of its involvement in brain development has led to speculation that it could be involved in the etiology of schizophrenia, identifying it as a potential therapy in combination with antipsychotics. Future directions and potential problems that should be considered in studies on D-amino acids and their relevant enzymes in schizophrenia are discussed. Full article
(This article belongs to the Section Molecular Medicine)
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20 pages, 12384 KB  
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
Cited by 2 | Viewed by 1731
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 KB  
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
Cited by 2 | Viewed by 2069
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 KB  
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
Cited by 3 | Viewed by 1895
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 KB  
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 15 | Viewed by 10206
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 KB  
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
Cited by 5 | Viewed by 3041
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 KB  
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 4 | Viewed by 4999
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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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 5 | Viewed by 1831
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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