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20 pages, 1729 KiB  
Article
Melatonin During Pre-Maturation and Its Effects on Bovine Oocyte Competence
by Laryssa Ketelyn Lima Pimenta, Nayara Ribeiro Kussano, José Eduardo Vieira Chaves, Hallya Beatriz Sousa Amaral, Maurício Machaim Franco, José Felipe Warmling Sprícigo and Margot Alves Nunes Dode
Antioxidants 2025, 14(8), 969; https://doi.org/10.3390/antiox14080969 - 7 Aug 2025
Abstract
To minimize the deleterious effects of oxidative stress and improve oocyte competence, we assessed the impact of melatonin during in vitro pre-maturation (pre-IVM) in bovine cumulus–oocyte complexes (COCs). We compared three groups: control (conventional IVM), pre-IVM control (without melatonin), and pre-IVM + MTn [...] Read more.
To minimize the deleterious effects of oxidative stress and improve oocyte competence, we assessed the impact of melatonin during in vitro pre-maturation (pre-IVM) in bovine cumulus–oocyte complexes (COCs). We compared three groups: control (conventional IVM), pre-IVM control (without melatonin), and pre-IVM + MTn (with melatonin). The analyses included levels of reactive oxygen species (ROS), mitochondrial activity, oocyte lipid content, and the expression of genes related to oxidative stress and lipid metabolism in oocytes and cumulus cells. We also examined embryo quality by evaluating kinetics of development and gene expression. The pre-IVM + MTn group exhibited an increase (p ≤ 0.05) in ROS levels and a decrease (p ≤ 0.05) in lipid content, while maintaining mitochondrial activity similar (p > 0.05) to that of the control group. Regarding gene expression, the effect of pre-IVM, independent of melatonin, was characterized by a decrease in FABP3 transcripts in cumulus cells and reductions in GSS and NFE2L2 transcripts in oocytes (p ≤ 0.05). The pre-IVM + MTn group also displayed a decrease (p ≤ 0.05) in CAT and SOD2 transcript levels. In terms of embryonic development, the pre-IVM + MTn group achieved a higher blastocyst rate on D7 (p ≤ 0.05) compared to the control group (30.8% versus 25.8%), but with similar rates (p > 0.05) to the pre-IVM control group (30.8% versus 35.9%). However, there was a decrease in the levels of the PLAC8 transcript. This study indicates that, under the conditions tested, melatonin did not significantly benefit oocyte competence. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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24 pages, 2024 KiB  
Article
New Insights into the Synergistic Bioactivities of Zingiber officinale (Rosc.) and Humulus lupulus (L.) Essential Oils: Targeting Tyrosinase Inhibition and Antioxidant Mechanisms
by Hubert Sytykiewicz, Sylwia Goławska and Iwona Łukasik
Molecules 2025, 30(15), 3294; https://doi.org/10.3390/molecules30153294 - 6 Aug 2025
Abstract
Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in [...] Read more.
Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in skin-related applications, particularly through the modulation of melanin biosynthesis and protection of skin-relevant cells from oxidative damage—a primary contributor to hyperpigmentation disorders. Zingiber officinale Rosc. (ginger) and Humulus lupulus L. (hop) are medicinal plants widely recognized for their diverse pharmacological properties. To the best of our knowledge, this study provides the first report on the synergistic interactions between essential oils derived from these species (referred to as EOZ and EOH) offering novel insights into their combined bioactivity. The purpose of this study was to evaluate essential oils extracted from ginger rhizomes and hop strobiles with respect to the following: (1) chemical composition, determined by gas chromatography–mass spectrometry (GC-MS); (2) tyrosinase inhibitory activity; (3) capacity to inhibit linoleic acid peroxidation; (4) ABTS•+ radical scavenging potential. Furthermore, the study utilizes both the combination index (CI) and dose reduction index (DRI) as quantitative parameters to evaluate the nature of interactions and the dose-sparing efficacy of essential oil (EO) combinations. GC–MS analysis identified EOZ as a zingiberene-rich chemotype, containing abundant sesquiterpene hydrocarbons such as α-zingiberene, β-bisabolene, and α-curcumene, while EOH exhibited a caryophyllene diol/cubenol-type profile, dominated by oxygenated sesquiterpenes including β-caryophyllene-9,10-diol and 1-epi-cubenol. In vitro tests demonstrated that both oils, individually and in combination, showed notable anti-tyrosinase, radical scavenging, and lipid peroxidation inhibitory effects. These results support their multifunctional bioactivity profiles with possible relevance to skin care formulations, warranting further investigation. Full article
(This article belongs to the Special Issue Essential Oils—Third Edition)
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19 pages, 3503 KiB  
Article
Discovery of Hub Genes Involved in Seed Development and Lipid Biosynthesis in Sea Buckthorn (Hippophae rhamnoides L.) Using UID Transcriptome Sequencing
by Siyang Zhao, Chengjiang Ruan, Alexey A. Dmitriev and Hyun Uk Kim
Plants 2025, 14(15), 2436; https://doi.org/10.3390/plants14152436 - 6 Aug 2025
Abstract
Sea buckthorn is a vital woody oil species valued for its role in soil conservation and its bioactive seed oil, which is rich in unsaturated fatty acids and other compounds. However, low seed oil content and small seed size are the main bottlenecks [...] Read more.
Sea buckthorn is a vital woody oil species valued for its role in soil conservation and its bioactive seed oil, which is rich in unsaturated fatty acids and other compounds. However, low seed oil content and small seed size are the main bottlenecks restricting the development and utilization of sea buckthorn. In this study, we tested the seed oil content and seed size of 12 sea buckthorn cultivars and identified the key genes and transcription factors involved in seed development and lipid biosynthesis via the integration of UID RNA-seq (Unique Identifiers, UID), WGCNA (weighted gene co-expression network analysis) and qRT-PCR (quantitative real-time PCR) analysis. The results revealed five cultivars (CY02, CY11, CY201309, CY18, CY21) with significantly higher oil contents and five cultivars (CY10, CY201309, CY18, CY21, CY27) with significantly heavier seeds. A total of 10,873 genes were significantly differentially expressed between the S1 and S2 seed developmental stages of the 12 cultivars. WGCNA was used to identify five modules related to seed oil content and seed weight/size, and 417 candidate genes were screened from these modules. Among them, multiple hub genes and transcription factors were identified; for instance, ATP synthase, ATP synthase subunit D and Acyl carrier protein 1 were related to seed development; plastid–lipid-associated protein, acyltransferase-like protein, and glycerol-3-phosphate 2-O-acyltransferase 6 were involved in lipid biosynthesis; and transcription factors DOF1.2, BHLH137 and ERF4 were associated with seed enlargement and development. These findings provide crucial insights into the genetic regulation of seed traits in sea buckthorn, offering targets for future breeding efforts aimed at improving oil yield and quality. Full article
(This article belongs to the Special Issue Molecular Regulation of Seed Development and Germination)
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19 pages, 1080 KiB  
Article
Microplastic Bioaccumulation and Oxidative Stress in Key Species of the Bulgarian Black Sea: Ecosystem Risk Early Warning
by Albena Alexandrova, Svetlana Mihova, Elina Tsvetanova, Madlena Andreeva, Georgi Pramatarov, Georgi Petrov, Nesho Chipev, Valentina Doncheva, Kremena Stefanova, Maria Grandova, Hristiyana Stamatova, Elitsa Hineva, Dimitar Dimitrov, Violin Raykov and Petya Ivanova
Microplastics 2025, 4(3), 50; https://doi.org/10.3390/microplastics4030050 - 6 Aug 2025
Abstract
Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish [...] Read more.
Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish species of the Bulgarian Black Sea ecosystems. The target hydrobionts were collected from nine representative coastal habitats of the northern and southern aquatory. MPs were quantified microscopically, and OS biomarkers (lipid peroxidation, glutathione, and antioxidant enzymes) were analyzed spectrometrically in fish liver and gills and invertebrate soft tissues (STs). The specific OS (SOS) index was calculated as a composite indicator of the ecological impact, incl. MP effects. The results revealed species-specific MP bioaccumulation, with the highest concentrations in Palaemon adspersus, Rathke (1837) (0.99 ± 1.09 particles/g ST) and the least abundance in Bittium reticulatum (da Costa, 1778) (0.0033 ± 0.0025 particles/g ST). In Sprattus sprattus (Linnaeus, 1758), the highest accumulation of MPs was present (2.01 ± 2.56 particles/g muscle). The correlation analyses demonstrated a significant association between MP counts and catalase activity in all examined species. The SOS index varied among species, reflecting different stress responses, and this indicated that OS levels were linked to ecological conditions of the habitat and the species-specific antioxidant defense potential to overcome multiple stressors. These findings confirmed the importance of environmental conditions, including MP pollution and the evolutionarily developed capacity of marine organisms to tolerate and adapt to environmental stress. This study emphasizes the need for novel approaches in monitoring MPs and OS to better assess potential ecological risks. Full article
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14 pages, 2957 KiB  
Article
Histochemical Study of Enzyme Activity in the Digestive Tract of the Small-Spotted Catshark (Scyliorhinus canicula) and the Smooth-Hound (Mustelus mustelus)
by Lucija Devčić, Ivan Vlahek, Magdalena Palić, Valerija Benko, Siniša Faraguna, Marin Lovrić, Damir Valić and Snježana Kužir
Fishes 2025, 10(8), 386; https://doi.org/10.3390/fishes10080386 - 6 Aug 2025
Abstract
The small-spotted catshark and the smooth-hound are cartilaginous, carnivorous fish with similar depth ranges in their habitats. These two species are among the most abundant elasmobranchs in the Adriatic Sea and are frequently caught by local fishermen using longline fishing. Despite their ecological [...] Read more.
The small-spotted catshark and the smooth-hound are cartilaginous, carnivorous fish with similar depth ranges in their habitats. These two species are among the most abundant elasmobranchs in the Adriatic Sea and are frequently caught by local fishermen using longline fishing. Despite their ecological similarities, little is known about the physiological differences in their digestive processes. The study of enzymatic digestion in these ecologically relevant species helps to fill the knowledge gap in the understanding of nutrient processing in cartilaginous fish. Therefore, the aim of this study was to determine, measure and compare the enzymatic activity of alkaline phosphatase, acid phosphatase, non-specific esterase and aminopeptidase. Fish were caught in the central part of the Adriatic Sea between 2021 and 2023. A total of 60 adult individuals were analyzed, with samples taken from six parts of the digestive tract. Histochemical analysis of 1440 slides revealed clear differences in enzyme activity between the two species. In the small-spotted catshark, cellular protein degradation was most pronounced in esophagus, posterior stomach and rectum, whereas in the smooth-hound, it was concentrated in posterior stomach and spiral intestine. Cellular digestion of lipids in the small-spotted catshark appears to occur primarily in the stomach. The results of this study provide new insights into the distribution of cellular digestive enzymes in cartilaginous fish and emphasize the importance of studying the entire digestive tract as an integrated system rather than focusing on individual parts. This study fills an important knowledge gap and contributes to a deeper understanding of digestive physiology, which in turn has implications for species conservation and biological variability. Full article
(This article belongs to the Section Physiology and Biochemistry)
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12 pages, 2363 KiB  
Article
MCC950 Alleviates Fat Embolism-Induced Acute Respiratory Distress Syndrome Through Dual Modulation of NLRP3 Inflammasome and ERK Pathways
by Chin-Kuo Lin, Zheng-Wei Chen, Yu-Hao Lin, Cheng-Ta Yang, Chung-Sheng Shi, Chieh-Mo Lin, Tzu Hsiung Huang, Justin Ching Hsien Lu, Kwok-Tung Lu and Yi-Ling Yang
Int. J. Mol. Sci. 2025, 26(15), 7571; https://doi.org/10.3390/ijms26157571 - 5 Aug 2025
Abstract
Fat embolism is a critical medical emergency often resulting from long bone fractures or amputations, leading to acute respiratory distress syndrome (ARDS). The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is activated by reactive oxygen species and [...] Read more.
Fat embolism is a critical medical emergency often resulting from long bone fractures or amputations, leading to acute respiratory distress syndrome (ARDS). The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is activated by reactive oxygen species and tissue damage, contributing to inflammatory responses. This study examines the role of NLRP3 in fat embolism-induced ARDS and evaluates the therapeutic potential of MCC950, a selective NLRP3 antagonist. Fat embolism was induced by fatty micelle injection into the tail vein of Sprague Dawley rats. Pulmonary injury was assessed through lung weight gain as an edema indicator, NLRP3 expression via Western blot, and IL-1β levels using ELISA. Histological damage and macrophage infiltration were evaluated with hematoxylin and eosin staining. Fat embolism significantly increased pulmonary NLRP3 expression, lipid peroxidation, IL-1β release, and macrophage infiltration within four hours, accompanied by severe pulmonary edema. NLRP3 was localized in type I alveolar cells, co-localizing with aquaporin 5. Administration of MCC950 significantly reduced inflammatory responses, lipid peroxidation, pulmonary edema, and histological damage, while attenuating MAPK cascade phosphorylation of ERK and Raf. These findings suggest that NLRP3 plays a critical role in fat embolism-induced acute respiratory distress syndrome, and its inhibition by MCC950 may offer a promising therapeutic approach. Full article
(This article belongs to the Section Molecular Biology)
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16 pages, 4074 KiB  
Article
Exploring 6-aza-2-Thiothymine as a MALDI-MSI Matrix for Spatial Lipidomics of Formalin-Fixed Paraffin-Embedded Clinical Samples
by Natalia Shelly Porto, Simone Serrao, Greta Bindi, Nicole Monza, Claudia Fumagalli, Vanna Denti, Isabella Piga and Andrew Smith
Metabolites 2025, 15(8), 531; https://doi.org/10.3390/metabo15080531 - 5 Aug 2025
Abstract
Background/Objectives: In recent years, lipids have emerged as critical regulators of different disease processes, being involved in cancer pathogenesis, progression, and outcome. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) has significantly expanded the technology’s reach, enabling spatially resolved profiling of lipids directly [...] Read more.
Background/Objectives: In recent years, lipids have emerged as critical regulators of different disease processes, being involved in cancer pathogenesis, progression, and outcome. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) has significantly expanded the technology’s reach, enabling spatially resolved profiling of lipids directly from tissue, including formalin-fixed paraffin-embedded (FFPE) specimens. In this context, MALDI matrix selection is crucial for lipid extraction and ionization, influencing key aspects such as molecular coverage and sensitivity, especially in such specimens with already depleted lipid content. Thus, in this work, we aim to explore the feasibility of mapping lipid species in FFPE clinical samples with MALDI-MSI using 6-aza-2-thiothymine (ATT) as a matrix of choice. Methods: To do so, ATT performances were first compared to those two other matrices commonly used for lipidomic analyses, 2′,5′-dihydroxybenzoic acid (DHB) and Norharmane (NOR), on lipid standards. Results: As a proof-of-concept, we then assessed ATT’s performance for the MALDI-MSI analysis of lipids in FFPE brain sections, both in positive and negative ion modes, comparing results with those obtained from other commonly used dual-polarity matrices. In this context, ATT enabled the putative annotation of 98 lipids while maintaining a well-balanced detection of glycerophospholipids (60.2%) and sphingolipids (32.7%) in positive ion mode. It outperformed both DHB and NOR in the identification of glycolipids (3%) and fatty acids (4%). Additionally, ATT exceeded DHB in terms of total lipid count (62 vs. 21) and class diversity and demonstrated performance comparable to NOR in negative ion mode. Moreover, ATT was applied to a FFPE glioblastoma tissue microarray (TMA) evaluating the ability of this matrix to reveal biologically relevant lipid features capable of distinguishing normal brain tissue from glioblastoma regions. Conclusions: Altogether, the results presented in this work suggest that ATT is a suitable matrix for pathology imaging applications, even at higher lateral resolutions of 20 μm, not only for proteomic but also for lipidomic analysis. This could enable the use of the same matrix type for the analysis of both lipids and peptides on the same tissue section, offering a unique strategic advantage for multi-omics studies, while also supporting acquisition in both positive and negative ionization modes. Full article
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13 pages, 857 KiB  
Article
Orange Allergy Beyond LTP: IgE Recognition of Germin-like Proteins in Citrus Fruits
by M. Soledad Zamarro Parra, Montserrat Martínez-Gomaríz, Alan Hernández, Javier Alcover, Isabel Dobski, David Rodríguez, Ricardo Palacios and Antonio Carbonell
Curr. Issues Mol. Biol. 2025, 47(8), 621; https://doi.org/10.3390/cimb47080621 - 5 Aug 2025
Viewed by 24
Abstract
Orange allergy is estimated to account for up to 3–4% of food allergies. Major allergens identified in orange (Citrus sinensis) include Cit s 1 (germin-like protein) and Cit s 2 (profilin), while Cit s 3 (non-specific lipid transfer protein, nsLTP) and [...] Read more.
Orange allergy is estimated to account for up to 3–4% of food allergies. Major allergens identified in orange (Citrus sinensis) include Cit s 1 (germin-like protein) and Cit s 2 (profilin), while Cit s 3 (non-specific lipid transfer protein, nsLTP) and Cit s 7 (gibberellin-regulated protein) have also been described. The objective of this study was to investigate the presence and IgE-binding capacity of germin-like proteins in citrus fruits other than oranges. We describe five patients with immediate allergic reactions after orange ingestion. All patients underwent skin prick tests (SPT) to aeroallergens and common food allergens, prick-by-prick testing with orange, lemon, and mandarin (pulp, peel, seeds), total IgE, specific IgE (sIgE), anaphylaxis scoring (oFASS), and the Food Allergy Quality of Life Questionnaire (FAQLQ-AF). Protein extracts from peel and pulp of orange, lemon, and mandarin were analyzed by Bradford assay, SDS-PAGE, and IgE immunoblotting using patient sera. Selected bands were identified by peptide mass fingerprinting. A 23 kDa band was recognized by all five patients in orange (pulp and peel), lemon (peel), and mandarin (peel). This band was consistent with Cit s 1, a germin-like protein already annotated in the IUIS allergen database for orange but not for lemon or mandarin. Peptide fingerprinting confirmed the germin-like identity of the 23 kDa bands in all three citrus species. Germin-like proteins of approximately 23 kDa were identified as IgE-binding components in peel extracts of orange, lemon, and mandarin, and in orange pulp. These findings suggest a potential shared allergen across citrus species that may contribute to allergic reactions independent of LTP sensitization. Full article
(This article belongs to the Section Molecular Plant Sciences)
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12 pages, 1107 KiB  
Article
DHA–Triacylglycerol Accumulation in Tacrolimus-Induced Nephrotoxicity Identified by Lipidomic Profiling
by Sho Nishida, Tamaki Ishima, Daiki Iwami, Ryozo Nagai and Kenichi Aizawa
Int. J. Mol. Sci. 2025, 26(15), 7549; https://doi.org/10.3390/ijms26157549 - 5 Aug 2025
Viewed by 36
Abstract
Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial β-oxidation of fatty acids. To [...] Read more.
Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial β-oxidation of fatty acids. To further characterize metabolic alterations associated with this condition, we conducted an untargeted lipidomic analysis of renal tissues using a murine model of TAC nephrotoxicity. TAC (1 mg/kg/day) or saline was subcutaneously administered to male ICR mice for 28 days, and kidney tissues were harvested for comprehensive lipidomic profiling. Lipidomic analysis was performed with liquid chromatography–tandem mass spectrometry (p < 0.05, n = 5/group). Triacylglycerols (TGs) were the predominant lipid class identified. TAC-treated mice exhibited reduced levels of unsaturated TG species with low carbon numbers, whereas TGs with higher carbon numbers and various degrees of unsaturation were increased. All detected TGs containing docosahexaenoic acid (DHA) showed an increasing trend in TAC-treated kidneys. Although accumulation of polyunsaturated TGs has been previously observed in chronic kidney disease, the preferential increase in DHA-containing TGs appears to be a unique feature of TAC-induced nephrotoxicity. These results suggest that DHA-enriched TGs may serve as a metabolic signature of TAC nephrotoxicity and offer new insights into its pathophysiology. Full article
(This article belongs to the Special Issue Recent Molecular Trends and Prospects in Kidney Diseases)
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21 pages, 4907 KiB  
Article
Integrated Transcriptomic and Metabolomic Analysis Reveals the Molecular Mechanisms Involved in the Adaptations of Mandarin Fish (Siniperca chuatsi) to Compound Feed
by Yunyun Yan, Yuan Zhang, Junjian Dong, Fubao Wang, Hetong Zhang, Fengying Gao, Xing Ye, Chengbin Wu and Chengfei Sun
Fishes 2025, 10(8), 379; https://doi.org/10.3390/fishes10080379 - 4 Aug 2025
Viewed by 121
Abstract
Siniperca chuatsi is an important high-quality freshwater aquaculture species in China. In nature, it feeds exclusively on live food. In this study, domesticated juvenile S. chuatsi were divided into three groups and fed live food (group L), compound feed (group C), or [...] Read more.
Siniperca chuatsi is an important high-quality freshwater aquaculture species in China. In nature, it feeds exclusively on live food. In this study, domesticated juvenile S. chuatsi were divided into three groups and fed live food (group L), compound feed (group C), or a mixed diet (group M) for three months to investigate the molecular mechanisms underlying adaptation to compound feed. Histopathological examination revealed that compound feed consumption induced looser liver cell arrangement, hepatocyte morphological irregularities, and vacuolization. A total of 1033 and 1428 differentially expressed genes (DEGs), and 187 and 184 differential metabolites (DMs), were identified in the C vs. L and C vs. M groups, respectively. Transcriptomic analysis revealed that the significantly and commonly enriched metabolic pathways shared by both comparison groups were predominantly involved in amino acid, carbohydrate, and lipid metabolisms. Metabolomic analysis demonstrated that the significantly and commonly enriched metabolic pathways shared by both comparison groups were the arachidonic acid metabolism, linoleic acid metabolism, oxidative phosphorylation, and PPAR signalling pathways. Integrated omics analysis showed that the PPAR signalling pathway was the only significantly co-enriched pathway across both omics datasets. This study provides new insights into the molecular mechanisms of compound feed adaptation and provides theoretical support for selecting feed traits in S. chuatsi. Full article
(This article belongs to the Section Genetics and Biotechnology)
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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 188
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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15 pages, 1474 KiB  
Article
Decline in Serum Lysophosphatidylcholine Species in Patients with Severe Inflammatory Bowel Disease
by Hauke Christian Tews, Tanja Elger, Muriel Huss, Johanna Loibl, Arne Kandulski, Martina Müller, Marcus Höring, Gerhard Liebisch and Christa Buechler
J. Clin. Med. 2025, 14(15), 5485; https://doi.org/10.3390/jcm14155485 - 4 Aug 2025
Viewed by 177
Abstract
Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy [...] Read more.
Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease: Pathogenesis and Management Strategies)
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26 pages, 2221 KiB  
Article
Effects of ε-Poly-L-Lysine/Chitosan Composite Coating on the Storage Quality, Reactive Oxygen Species Metabolism, and Membrane Lipid Metabolism of Tremella fuciformis
by Junzheng Sun, Yingying Wei, Longxiang Li, Mengjie Yang, Yusha Liu, Qiting Li, Shaoxiong Zhou, Chunmei Lai, Junchen Chen and Pufu Lai
Int. J. Mol. Sci. 2025, 26(15), 7497; https://doi.org/10.3390/ijms26157497 - 3 Aug 2025
Viewed by 125
Abstract
This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated [...] Read more.
This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated by surface spraying, with distilled water serving as the control. The effects of the coating on storage quality, physicochemical properties, reactive oxygen species (ROS) metabolism, and membrane lipid metabolism were evaluated during storage at (25 ± 1) °C. The results showed that the ε-PL/CTS composite coating significantly retarded quality deterioration, as evidenced by reduced weight loss, maintained whiteness and color, and higher retention of soluble sugars, soluble solids, and soluble proteins. The coating also effectively limited water migration and loss. Mechanistically, the coated T. fuciformis exhibited enhanced antioxidant capacity, characterized by increased superoxide anion (O2) resistance capacity, higher activities of antioxidant enzymes (SOD, CAT, APX), and elevated levels of non-enzymatic antioxidants (AsA, GSH). This led to a significant reduction in malondialdehyde (MDA) accumulation, alongside improved DPPH radical scavenging activity and reducing power. Furthermore, the ε-PL/CTS coating preserved cell membrane integrity by inhibiting the activities of lipid-degrading enzymes (lipase, LOX, PLD), maintaining higher levels of key phospholipids (phosphatidylinositol and phosphatidylcholine), delaying phosphatidic acid accumulation, and consequently reducing cell membrane permeability. In conclusion, the ε-PL/CTS composite coating effectively extends the shelf life and maintains the quality of postharvest T. fuciformis by modulating ROS metabolism and preserving membrane lipid homeostasis. This study provides a theoretical basis and a practical approach for the quality control of fresh T. fuciformis. Full article
(This article belongs to the Section Biochemistry)
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59 pages, 1351 KiB  
Review
The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
Int. J. Mol. Sci. 2025, 26(15), 7498; https://doi.org/10.3390/ijms26157498 - 3 Aug 2025
Viewed by 173
Abstract
Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce [...] Read more.
Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies. Full article
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22 pages, 1641 KiB  
Article
Site-Specific Trafficking of Lipid and Polar Metabolites in Adipose and Muscle Tissue Reveals the Impact of Bariatric Surgery-Induced Weight Loss: A 6-Month Follow-Up Study
by Aidan Joblin-Mills, Zhanxuan E. Wu, Garth J. S. Cooper, Ivana R. Sequeira-Bisson, Jennifer L. Miles-Chan, Anne-Thea McGill, Sally D. Poppitt and Karl Fraser
Metabolites 2025, 15(8), 525; https://doi.org/10.3390/metabo15080525 - 2 Aug 2025
Viewed by 277
Abstract
Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not [...] Read more.
Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not known. Methods: Women with obesity scheduled to undergo bariatric surgery were assessed at baseline (BL, n = 28) and at 6-month follow-up (6m_FU, n = 26) after weight loss. Fasting plasma (Pla), subcutaneous thigh adipose (STA), subcutaneous abdominal adipose, (SAA), and thigh vastus lateralis muscle (VLM) samples were collected at BL through surgery and at 6m_FU using needle biopsy. An untargeted liquid chromatography mass spectrometry metabolomics platform was used. Pla and tissue-specific lipid and polar metabolite profiles were modelled as changes from BL and 6m_FU. Results: There was significant body weight (−24.5 kg) loss at 6m_FU (p < 0.05). BL vs. 6m_FU tissue metabolomics profiles showed the largest difference in lipid profiles in SAA tissue in response to surgery. Conversely, polar metabolites were more susceptible to change in STA and VLM. In Pla samples, both lipid and polar metabolite profiles showed significant differences between timepoints. Jaccard–Tanimoto coefficient t-tests identified a sub-group of gut microbiome and dietary-derived omega-3-fatty-acid-containing lipid species and core energy metabolism and adipose catabolism-associated polar metabolites that are trafficked between sample types in response to bariatric surgery. Conclusions: In this first report on channelling of lipids and polar metabolites to alternative tissues in bariatric-induced weight loss, adaptive shuttling of small molecules was identified, further promoting adipose processing and highlighting the dynamic and coordinated nature of post-surgical metabolic regulation. Full article
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