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24 pages, 6731 KiB  
Article
Combined Impacts of Acute Heat Stress on the Histology, Antioxidant Activity, Immunity, and Intestinal Microbiota of Wild Female Burbot (Lota Lota) in Winter: New Insights into Heat Sensitivity in Extremely Hardy Fish
by Cunhua Zhai, Yutao Li, Ruoyu Wang, Haoxiang Han, Ying Zhang and Bo Ma
Antioxidants 2025, 14(8), 947; https://doi.org/10.3390/antiox14080947 (registering DOI) - 31 Jul 2025
Viewed by 265
Abstract
Temperature fluctuations caused by climate change and global warming pose a threat to fish. The burbot (lota lota) population is particularly sensitive to increased water temperature, but the systematic impacts of high-temperature exposure on their liver and intestinal health remain unclear. [...] Read more.
Temperature fluctuations caused by climate change and global warming pose a threat to fish. The burbot (lota lota) population is particularly sensitive to increased water temperature, but the systematic impacts of high-temperature exposure on their liver and intestinal health remain unclear. In January of 2025, we collected wild adult burbot individuals from the Ussuri River (water temperature: about 2 °C), China. The burbot were exposed to 2 °C, 7 °C, 12 °C, 17 °C, and 22 °C environments for 96 h; then, the liver and intestinal contents were subsequently collected for histopathology observation, immunohistochemistry, biochemical index assessment, and transcriptome/16S rDNA sequencing analysis. There was obvious liver damage including hepatocyte necrosis, fat vacuoles, and cellular peripheral nuclei. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were elevated and subsequently decreased. Additionally, the malondialdehyde (MDA) level significantly increased with increasing temperature. These results indicate that 7 °C (heat stress temperature), 12 °C (tipping point for normal physiological metabolism status), 17 °C (tipping point for individual deaths), and 22 °C (thermal limit) are critical temperatures in terms of the physiological response of burbot during their breeding period. In the hepatic transcriptome profiling, 6538 differentially expressed genes (DEGs) were identified, while KEGG enrichment analysis showed that high-temperature stress could affect normal liver function by regulating energy metabolism, immune, and apoptosis-related pathways. Microbiomics also revealed that acute heat stress could change the intestinal microbe community structure. Additionally, correlation analysis suggested potential regulatory relationships between intestinal microbe taxa and immune/apoptosis-related DEGs in the liver. This study revealed the potential impact of environmental water temperature changes in cold habitats in winter on the physiological adaptability of burbot during the breeding period and provides new insights for the ecological protection of burbot in the context of global climate change and habitat warming. Full article
(This article belongs to the Special Issue Antioxidant Response in Aquatic Animals)
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33 pages, 3764 KiB  
Article
Cu2+ and Zn2+ Ions Affecting Biochemical Paths and DNA Methylation of Rye (Secale cereale L.) Anther Culture Influencing Plant Regeneration Efficiency
by Wioletta Monika Dynkowska, Renata Orłowska, Piotr Waligórski and Piotr Tomasz Bednarek
Cells 2025, 14(15), 1167; https://doi.org/10.3390/cells14151167 - 29 Jul 2025
Viewed by 150
Abstract
Rye regeneration in anther cultures is problematic and affected by albino plants. DNA methylation changes linked to Cu2+ ions in the induction medium affect reprogramming microspores from gametophytic to sporophytic path. Alternations in S-adenosyl-L-methionine (SAM), glutathione (GSH), or β-glucans and changes in [...] Read more.
Rye regeneration in anther cultures is problematic and affected by albino plants. DNA methylation changes linked to Cu2+ ions in the induction medium affect reprogramming microspores from gametophytic to sporophytic path. Alternations in S-adenosyl-L-methionine (SAM), glutathione (GSH), or β-glucans and changes in DNA methylation in regenerants obtained under different in vitro culture conditions suggest a crucial role of biochemical pathways. Thus, understanding epigenetic and biochemical changes arising from the action of Cu2+ and Zn2+ that participate in enzymatic complexes may stimulate progress in rye doubled haploid plant regeneration. The Methylation-Sensitive Amplified Fragment Length Polymorphism approach was implemented to identify markers related to DNA methylation and sequence changes following the quantification of variation types, including symmetric and asymmetric sequence contexts. Reverse-Phase High-Pressure Liquid Chromatography (RP-HPLC) connected with mass spectrometry was utilized to determine SAM, GSH, and glutathione disulfide, as well as phytohormones, and RP-HPLC with a fluorescence detector to study polyamines changes originating in rye regenerants due to Cu2+ or Zn2+ presence in the induction medium. Multivariate and regression analysis revealed that regenerants derived from two lines treated with Cu2+ and those treated with Zn2+ formed distinct groups based on DNA sequence and methylation markers. Zn2+ treated and control samples formed separate groups. Also, Cu2+ discriminated between controls and treated samples, but the separation was less apparent. Principal coordinate analysis explained 85% of the total variance based on sequence variation and 69% of the variance based on DNA methylation changes. Significant differences in DNA methylation characteristics were confirmed, with demethylation in the CG context explaining up to 89% of the variance across genotypes. Biochemical profiles also demonstrated differences between controls and treated samples. The changes had different effects on green and albino plant regeneration efficiency, with cadaverine (Cad) and SAM affecting regeneration parameters the most. Analyses of the enzymes depend on the Cu2+ or Zn2+ ions and are implemented in the synthesis of Cad, or SAM, which showed that some of them could be candidates for genome editing. Alternatively, manipulating SAM, GSH, and Cad may improve green plant regeneration efficiency in rye. Full article
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28 pages, 5315 KiB  
Article
Integrated Transcriptome and Metabolome Analysis Provides Insights into the Low-Temperature Response in Sweet Potato (Ipomoea batatas L.)
by Zhenlei Liu, Jiaquan Pan, Sitong Liu, Zitong Yang, Huan Zhang, Tao Yu and Shaozhen He
Genes 2025, 16(8), 899; https://doi.org/10.3390/genes16080899 - 28 Jul 2025
Viewed by 326
Abstract
Background/Objectives: Sweet potato is a tropical and subtropical crop and its growth and yield are susceptible to low-temperature stress. However, the molecular mechanisms underlying the low temperature stress of sweetpotato are unknown. Methods: In this work, combined transcriptome and metabolism analysis was employed [...] Read more.
Background/Objectives: Sweet potato is a tropical and subtropical crop and its growth and yield are susceptible to low-temperature stress. However, the molecular mechanisms underlying the low temperature stress of sweetpotato are unknown. Methods: In this work, combined transcriptome and metabolism analysis was employed to investigate the low-temperature responses of two sweet potato cultivars, namely, the low-temperature-resistant cultivar “X33” and the low-temperature-sensitive cultivar “W7”. Results: The differentially expressed metabolites (DEMs) of X33 at different time stages clustered in five profiles, while they clustered in four profiles of W7 with significant differences. Differentially expressed genes (DEGs) in X33 and W7 at different time points clustered in five profiles. More DEGs exhibited continuous or persistent positive responses to low-temperature stress in X33 than in W7. There were 1918 continuously upregulated genes and 6410 persistent upregulated genes in X33, whereas 1781 and 5804 were found in W7, respectively. Core genes involved in Ca2+ signaling, MAPK cascades, the reactive oxygen species (ROS) signaling pathway, and transcription factor families (including bHLH, NAC, and WRKY) may play significant roles in response to low temperature in sweet potato. Thirty-one common differentially expressed metabolites (DEMs) were identified in the two cultivars in response to low temperature. The KEGG analysis of these common DEMs mainly belonged to isoquinoline alkaloid biosynthesis, phosphonate and phosphinate metabolism, flavonoid biosynthesis, cysteine and methionine metabolism, glycine, serine, and threonine metabolism, ABC transporters, and glycerophospholipid metabolism. Five DEMs with identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected for correlation analysis. KEGG enrichment analysis showed that the carbohydrate metabolism, phenylpropanoid metabolism, and glutathione metabolism pathways were significantly enriched and played vital roles in low-temperature resistance in sweet potato. Conclusions: These findings contribute to a deeper understanding of the molecular mechanisms underlying plant cold tolerance and offer targets for molecular breeding efforts to enhance low-temperature resistance. Full article
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12 pages, 2911 KiB  
Article
A pH-Sensitive Glutathione Responsive Small-Molecule Probe TZ2 Sensitizes Lung Cancer Cells to Chemotherapy by Targeting Tumor Microenvironment
by Changle Zhong, Minghan Lu, Guanhao Pan, Xintong You, Yan Peng, Shulan Zeng and Guohai Zhang
Molecules 2025, 30(15), 3081; https://doi.org/10.3390/molecules30153081 - 23 Jul 2025
Viewed by 193
Abstract
The tumor microenvironment plays an important role in tumor incidence, metastasis, and chemotherapy resistance. Novel therapeutic strategies targeting the tumor microenvironment have become a research focus in the field of biomedicine. In this study, we developed a smart small-molecule probe, TZ2, featuring [...] Read more.
The tumor microenvironment plays an important role in tumor incidence, metastasis, and chemotherapy resistance. Novel therapeutic strategies targeting the tumor microenvironment have become a research focus in the field of biomedicine. In this study, we developed a smart small-molecule probe, TZ2, featuring pH/GSH dual-responsive characteristics. TZ2 exhibits a unique pH-dependent reaction mechanism: GSH is preferentially covalently modified with maleimide groups in acidic microenvironments (pH < 7), while specifically activating nucleophilic substitutions under alkaline conditions (pH > 7). It is worth noting that TZ2 effectively eliminates intracellular glutathione (GSH) in a time and concentration-dependent manner, demonstrating significant GSH depletion ability in various tumor cell lines. Pharmacodynamic studies have shown that TZ2 not only inhibits the cell cycle by regulating the expression of cell cycle-related proteins, but also effectively suppresses the cloning ability of cancer cells. Furthermore, TZ2 significantly increases the sensitivity of drug-resistant cancer cells to cisplatin. By integrating microenvironment modulation, real-time monitoring, and synergistic therapy, TZ2 provides a novel molecular tool and theoretical basis for tumor theranostics integration. Full article
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19 pages, 4583 KiB  
Article
Glutathione and Magnetic Nanoparticle-Modified Nanochannels for the Detection of Cadmium (II) in Cereal Grains
by Wei Hu, Xinyue Xiang, Donglei Jiang, Na Zhang and Lifeng Wang
Magnetochemistry 2025, 11(7), 61; https://doi.org/10.3390/magnetochemistry11070061 - 21 Jul 2025
Viewed by 242
Abstract
We developed a novel and portable magnetic nanochannel electrochemical sensor for the sensitive detection of cadmium ions (Cd2+), which pose serious risks to food safety and human health. The sensor was fabricated by co-modifying an anodic aluminum oxide (AAO) nanochannel membrane [...] Read more.
We developed a novel and portable magnetic nanochannel electrochemical sensor for the sensitive detection of cadmium ions (Cd2+), which pose serious risks to food safety and human health. The sensor was fabricated by co-modifying an anodic aluminum oxide (AAO) nanochannel membrane with a composite of glutathione (GSH) and ferric oxide nanoparticles (Fe3O4), denoted as GSH@Fe3O4. This modified membrane was then integrated with a screen-printed carbon electrode (SPCE) to construct the GSH@Fe3O4/GSH@AAO/SPCE sensing platform. The performance of the sensor was evaluated using differential pulse voltammetry (DPV), which demonstrated a strong linear correlation between the peak current response and the concentration of Cd2+ in the range of 5–120 μg/L. The calibration equation was IDPV(μA) = −0.31 + 0.98·CCd2+(μg/L), with an excellent correlation coefficient (R2 = 0.999, n = 3). The calculated limit of detection (LOD) was as low as 0.1 μg/L, indicating the high sensitivity of the system. These results confirm the successful construction of the GSH@Fe3O4/GSH@AAO/SPCE portable nanochannel sensor. This innovative sensing platform provides a rapid, sensitive, and user-friendly approach for the on-site monitoring of heavy metal contamination in agricultural products, especially grains. Full article
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33 pages, 2362 KiB  
Review
Ferroptosis and Metabolic Dysregulation: Emerging Chemical Targets in Cancer and Infection
by Marta Pawłowska, Jarosław Nuszkiewicz, Dorian Julian Jarek and Alina Woźniak
Molecules 2025, 30(14), 3020; https://doi.org/10.3390/molecules30143020 - 18 Jul 2025
Viewed by 628
Abstract
The distinctive nature of ferroptosis is that it is induced chemically and signifies a regulated cell death dependent on iron-dependent lipid peroxidation. The mechanism of ferroptosis involves oxidative damage to the membrane lipids. It differs from apoptosis and necroptosis, triggering metabolic changes in [...] Read more.
The distinctive nature of ferroptosis is that it is induced chemically and signifies a regulated cell death dependent on iron-dependent lipid peroxidation. The mechanism of ferroptosis involves oxidative damage to the membrane lipids. It differs from apoptosis and necroptosis, triggering metabolic changes in the iron-lipid homeostasis and antioxidant defense, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4). Herein, the molecular mechanisms of ferroptosis and its role in the tumorigenesis process and infection-related diseases are presented. It also discusses metabolic reprogramming as a factor that modifies the levels of cell-sensitizing polyunsaturated fatty acids (PUFAs), iron dysregulation, and oxidative stress in aggressive cancers and inflammatory diseases such as sepsis, tuberculosis, and COVID-19. Particular attention is given to chemical modulators of ferroptosis, including synthetic inducers and inhibitors, as well as bioactive natural compounds. Our focus is on the significance of analytical tools, such as lipidomics and metabolomics, in understanding the phenomenon of ferroptosis. Finally, we explore novel therapeutic approaches targeting ferroptosis in cancer and infectious diseases, while navigating both the opportunities and challenges in drug development. The review then draws on chemical biology and disease pathology to propose promising areas of study for ferroptosis-related therapies. Full article
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26 pages, 1644 KiB  
Review
Therapeutic Targeting of Apoptosis, Autophagic Cell Death, Necroptosis, Pyroptosis, and Ferroptosis Pathways in Oral Squamous Cell Carcinoma: Molecular Mechanisms and Potential Strategies
by Po-Chih Hsu, Chung-Che Tsai, Ya-Hsuan Lin and Chan-Yen Kuo
Biomedicines 2025, 13(7), 1745; https://doi.org/10.3390/biomedicines13071745 - 16 Jul 2025
Viewed by 466
Abstract
Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with poor prognosis, largely due to its high metastatic potential and resistance to conventional therapies. Recent advances in cancer biology have underscored the significance of regulated cell death pathways, including apoptosis, autophagic [...] Read more.
Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with poor prognosis, largely due to its high metastatic potential and resistance to conventional therapies. Recent advances in cancer biology have underscored the significance of regulated cell death pathways, including apoptosis, autophagic cell death (ACD), necroptosis, pyroptosis, and ferroptosis, in modulating tumor progression and therapeutic responses. This review provides the current insights into the molecular mechanisms underlying these cell death pathways and explores their therapeutic relevance in OSCC. Restoration of apoptosis using BH3 mimetics, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor agonists, and p53 reactivators shows promise for sensitizing OSCC cells to treatment. Autophagy plays context-dependent roles in cancer, acting as a tumor suppressor during early carcinogenesis by maintaining cellular homeostasis, and as a tumor promoter in established tumors by supporting cancer cell survival under stress. Targeting necroptosis and pyroptosis has emerged as a novel strategy for inducing cancer cell death, with compounds such as acetylshikonin and okanin demonstrating antitumor effects. Additionally, the induction of ferroptosis via lipid peroxidation and glutathione peroxidase 4 (GPX4) inhibition offers a promising avenue for overcoming drug resistance, with agents such as quercetin and trifluoperazine exhibiting preclinical success. Integration of these therapeutic approaches may enhance the OSCC treatment efficacy, reduce chemoresistance, and provide novel prognostic biomarkers for clinical management. Future studies should focus on optimizing combinatorial strategies that effectively leverage these pathways to improve OSCC patient outcomes. Full article
(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approach)
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18 pages, 2273 KiB  
Article
Integrating Near-Infrared Spectroscopy and Proteomics for Semen Quality Biosensing
by Notsile H. Dlamini, Mariana Santos-Rivera, Carrie K. Vance-Kouba, Olga Pechanova, Tibor Pechan and Jean M. Feugang
Biosensors 2025, 15(7), 456; https://doi.org/10.3390/bios15070456 - 15 Jul 2025
Viewed by 403
Abstract
Artificial insemination (AI) is a key breeding technique in the swine industry; however, the lack of reliable biomarkers for semen quality limits its effectiveness. Seminal plasma (SP) contains extracellular vesicles (EVs) that present a promising, non-invasive biomarker for semen quality. This study explores [...] Read more.
Artificial insemination (AI) is a key breeding technique in the swine industry; however, the lack of reliable biomarkers for semen quality limits its effectiveness. Seminal plasma (SP) contains extracellular vesicles (EVs) that present a promising, non-invasive biomarker for semen quality. This study explores the biochemical profiles of boar SP to assess semen quality through near-infrared spectroscopy (NIRS) and proteomics of SP-EVs. Fresh semen from mature Duroc boars was evaluated based on sperm motility, classifying samples as Passed (≥70%) or Failed (<70%). NIRS analysis identified distinct variations in water structures at specific wavelengths (C1, C5, C12 nm), achieving high accuracy (92.2%), sensitivity (94.2%), and specificity (90.3%) through PCA-LDA. Proteomic analysis of SP-EVs revealed 218 proteins in Passed and 238 in Failed samples. Nexin-1 and seminal plasma protein pB1 were upregulated in Passed samples, while LGALS3BP was downregulated. The functional analysis highlighted pathways associated with single fertilization, filament organization, and glutathione metabolism in Passed samples. Integrating NIRS with SP-EV proteomics provides a robust approach to non-invasive assessment of semen quality. These findings suggest that SP-EVs could serve as effective biosensors for rapid semen quality assessment, enabling better boar semen selection and enhancing AI practices in swine breeding. Full article
(This article belongs to the Section Optical and Photonic Biosensors)
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22 pages, 5335 KiB  
Article
An Italian Study of PM0.5 Toxicity: In Vitro Investigation of Cytotoxicity, Oxidative Stress, Intercellular Communication, and Extracellular Matrix Metalloproteases
by Nathalie Steimberg, Giovanna Mazzoleni, Jennifer Boniotti, Milena Villarini, Massimo Moretti, Annalaura Carducci, Marco Verani, Tiziana Grassi, Francesca Serio, Sara Bonetta, Elisabetta Carraro, Alberto Bonetti, Silvia Bonizzoni, Umberto Gelatti and the MAPEC_LIFE Study Group
Int. J. Mol. Sci. 2025, 26(14), 6769; https://doi.org/10.3390/ijms26146769 - 15 Jul 2025
Viewed by 208
Abstract
Particulate matter (PM), mainly PM0.5, represents a significant concern for human health, particularly relating to lung homeostasis, and more research is required to ascertain its tissue tropism and the molecular pathways involved. In this study, we first focus on classical in [...] Read more.
Particulate matter (PM), mainly PM0.5, represents a significant concern for human health, particularly relating to lung homeostasis, and more research is required to ascertain its tissue tropism and the molecular pathways involved. In this study, we first focus on classical in vitro toxicological endpoints (cytotoxicity and cell growth) in human bronchial and alveolar epithelial cell lines mimicking the two pulmonary target tissues. Air samples were collected in five Italian cities (Brescia, Lecce, Perugia, Pisa, Turin) during winter and spring. To better decipher the PM0.5 effects on pulmonary cells, a further winter sampling was performed in Brescia, and studies were extended to assess tumour promotion, oxidative stress, and the activity of Matrix metalloproteases (MMP). The results confirmed that the effect of air pollution is linked to the seasons (winter is usually more cytotoxic than spring) and is correlated with the peculiar characteristics of the cities studied (meteoclimatic conditions, economic/anthropogenic activities). Alveolar cells were often less sensitive than bronchial cells. All PM samples from Brescia inhibited intercellular communication mediated by gap junctions (GJIC), increased the total content in glutathione, and decreased the reduced form of glutathione, whereas the Reactive Oxygen Species (ROS) content was almost constant. Long-term treatments at higher doses of PM decreased MMP2 and MMP9 activity. Taken together, the results confirmed that PM is cytotoxic and can potentially act as tumour promoters, but the mechanisms involved in oxidative stress and lung homeostasis are dose- and time-dependent and quite complex. Full article
(This article belongs to the Special Issue The Influence of Environmental Factors on Disease and Health Outcomes)
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15 pages, 2940 KiB  
Article
Platinum Nanoparticles Loaded in Polydopamine-Modified Porous Coordination Network-224 with Peroxidase-Like Activity for Sensitive Glutathione Detection
by Shoubei Gao, Mingyue Gao, Chenran Zhen, Yanshuai Cui, Xianbing Ji, Ruyu Li and Longgang Wang
Biomolecules 2025, 15(7), 1002; https://doi.org/10.3390/biom15071002 - 13 Jul 2025
Viewed by 344
Abstract
The content of glutathione in the human body is crucial to human health, so a convenient and efficient method is needed to detect it. Herein, porous coordination network-224 (PCN-224) was modified by polydopamine to prepare polydopamine-modified PCN-224 (PCN-224-PDA) to improve the water dispersibility [...] Read more.
The content of glutathione in the human body is crucial to human health, so a convenient and efficient method is needed to detect it. Herein, porous coordination network-224 (PCN-224) was modified by polydopamine to prepare polydopamine-modified PCN-224 (PCN-224-PDA) to improve the water dispersibility of the PCN-224. Monodispersed platinum nanoparticles were loaded into the PCN-224-PDA to prepare PCN-224-PDA-Pt. The PCN-224-PDA-Pt showed high peroxidase-like catalytic activity, and its catalytic activity was affected by pH and temperature. The PCN-224-PDA-Pt almost had no hemolysis of red blood cells. In addition, the PCN-224-PDA-Pt showed high affinity for 3,3′,5,5′-tetramethylbenzidine and catalytic efficiency in kinetic studies, and the type of reactive oxygen species generated during the catalytic process was hydroxyl radicals. More importantly, a colorimetric method for glutathione detection was developed based on the peroxidase-like activity of the PCN-224-PDA-Pt. The linear detection range was 1–600 μM and the detection limit reached 0.306 μM. This method shows good anti-interference capabilities and excellent recovery rates, indicating its strong potential for applications in biological detection. Full article
(This article belongs to the Section Chemical Biology)
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18 pages, 3104 KiB  
Article
Reduced Glutathione in Modulation of Salt Stress on Sour Passion Fruit Production and Quality
by Weslley Bruno Belo de Souza, Geovani Soares de Lima, Lauriane Almeida dos Anjos Soares, Mirandy dos Santos Dias, Brencarla de Medeiros Lima, Larissa Fernanda Souza Santos, Valeska Karolini Nunes Oliveira, Rafaela Aparecida Frazão Torres, Hans Raj Gheyi, Lucyelly Dâmela Araújo Borborema, André Alisson Rodrigues da Silva, Vitor Manoel Bezerra da Silva and Valéria Fernandes de Oliveira Sousa
Plants 2025, 14(14), 2149; https://doi.org/10.3390/plants14142149 - 11 Jul 2025
Viewed by 408
Abstract
This study evaluated the effects of reduced glutathione (GSH) application on the production and quality of sour passion fruit irrigated with brackish water in the semi-arid region of Paraíba, Brazil. The experiment was conducted in drainage lysimeters under greenhouse conditions at the Center [...] Read more.
This study evaluated the effects of reduced glutathione (GSH) application on the production and quality of sour passion fruit irrigated with brackish water in the semi-arid region of Paraíba, Brazil. The experiment was conducted in drainage lysimeters under greenhouse conditions at the Center of Technology and Natural Resources of the Federal University of Campina Grande (UFCG). Treatments combined five levels of electrical conductivity of brackish irrigation water (Bw: 0.4, 1.2, 2.0, 2.8, and 3.6 dS m−1) and four GSH concentrations (0, 40, 80, and 120 mg L−1), arranged in a randomized block design with three replicates. Salinity levels above 0.4 dS m−1 negatively affected fruit production and post-harvest quality of ‘BRS GA1’ sour passion fruit. Foliar application of 120 mg L−1 GSH increased fruit yield, while 74 mg L−1 GSH mitigated salt stress effects on production and pulp chemical quality. The ‘BRS GA1’ cultivar was highly sensitive to salinity, showing a 26.9% yield reduction per unit increase in Bw electrical conductivity above 0.4 dS m−1. The results suggest that GSH can alleviate salt stress damage, improving crop productivity and fruit quality under semi-arid conditions. Full article
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21 pages, 2210 KiB  
Article
Thiamine Compounds Alleviate Oxidative Stress, Over-Expression of Pro-Inflammatory Markers and Behavioral Abnormalities in a Mouse Predation Model of PTSD
by Tatyana Strekalova, Anna Gorlova, Joao Costa-Nunes, Aleksandr Litavrin, Johannes P. M. de Munter, Alexei Lyundup, Aleksei Umriukhin, Andrey Proshin, Allan V. Kalueff, Edna Grünblatt and Susanna Walitza
Int. J. Mol. Sci. 2025, 26(14), 6627; https://doi.org/10.3390/ijms26146627 - 10 Jul 2025
Viewed by 418
Abstract
Experiences of life-threatening stimuli can induce post-traumatic stress disorder (PTSD), which is associated with long-lasting behavioral and neurochemical abnormalities. Despite its increased global incidence, the current treatment options for PTSD remain limited, highlighting the need for novel therapeutic strategies. As oxidative stress and [...] Read more.
Experiences of life-threatening stimuli can induce post-traumatic stress disorder (PTSD), which is associated with long-lasting behavioral and neurochemical abnormalities. Despite its increased global incidence, the current treatment options for PTSD remain limited, highlighting the need for novel therapeutic strategies. As oxidative stress and neuroinflammation contribute to PTSD, the use of powerful antioxidants such as thiamine (B1 vitamin) compounds may counteract disease development. Young C57BL/6 mice received thiamine or benfotiamine in drinking water (each at a dose of 200 mg/kg/day) for 21 days, and for the last five days, they were subjected to rat exposure. Mice were studied for anxiety-like behavior, exploration, locomotion, grooming, social interactions, pain sensitivity, brain changes in protein carbonyl (PC), total glutathione (TG), and gene expression of distress and inflammation markers. Rat exposure induced anxiety-like behavior, excessive grooming, and alteration in locomotion, along with other abnormalities. Stressed, untreated mice had elevated levels of PC and TG in the prefrontal cortex, hippocampus, amygdala, and striatum and increased expression of Il-1β, Tnf, c-Fos, Cox-1, and Cox-2. Treatment with thiamine or benfotiamine significantly ameliorated most of these changes in the stressed groups. Thus, thiamine compounds may have therapeutic potential in patients with PTSD, owing to their antioxidant and anti-inflammatory properties. Full article
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20 pages, 6441 KiB  
Article
Tissue-Based Metabolomic Profiling of Endometrial Cancer and Hyperplasia
by Khalid Akkour, Afshan Masood, Maha Al Mogren, Reem H. AlMalki, Assim A. Alfadda, Salini Scaria Joy, Ali Bassi, Hani Alhalal, Maria Arafah, Othman Mahmoud Othman, Hadeel Mohammad Awwad, Anas M. Abdel Rahman and Hicham Benabdelkamel
Metabolites 2025, 15(7), 458; https://doi.org/10.3390/metabo15070458 - 5 Jul 2025
Viewed by 667
Abstract
Background: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. Methods: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) [...] Read more.
Background: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. Methods: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) (n = 20). Tissue was collected from the endometrium of all 54 patients, including patients with HY, EC, and CO, who underwent total hysterectomy. EC and HY diagnoses were confirmed based on histological examination. Untargeted metabolomics profiling was conducted using LC-HRMS. The partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for univariate and multivariate statistical analysis. The fitness of the model (R2Y) and predictive ability (Q2) were used to create OPLS-DA models. ROC analysis was carried out, followed by network analysis using Ingenuity Pathway Analysis. Results: The top metabolites that can discriminate EC and HY from CO were identified. This revealed a decrease in the levels of the lipid species, specifically phosphatidic acid (PA) (PA (14:1/14:0), PA(10:0/17:0), PA(18:1-O(12,13)/12:0)), PG(a-13:0/a-13:0), ganglioside GA1 (d18:1/18:1), PS(14:1/14:0), TG(20:0/18:4/14:1), and CDP-DG(PGF2alpha/18:2), while the levels of 3-Dehydro-L-gulonate, Uridine diphosphate-N-acetylglucosamine, ganglioside GT2 (d18:1/14:0), gamma-glutamyl glutamic acid and oxidized glutathione were increased in cases of EC and HY as compared to CO. Bioinformatics analysis, specifically using Ingenuity Pathway Analysis (IPA), revealed distinct pathway enrichments for EC and HY. For EC, the most highly scored pathways were associated with cell-to-cell signaling and interaction, skeletal and muscular system development and function, and small-molecule biochemistry. In contrast, HY cases showed the highest scoring pathways related to inflammatory disease, inflammatory response, and organismal injury and abnormalities. Conclusions: Developing sensitive biomarkers could improve diagnosis and guide treatment decisions, particularly in identifying which patients with HY may safely avoid hysterectomy and be managed with hormonal therapy. Full article
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16 pages, 2795 KiB  
Article
Therapeutic Potential of 7,8-Dimethoxycoumarin in Tumor Necrosis Factor-Alpha-Induced Trigeminal Neuralgia in a Rat Model
by Nallupillai Paramakrishnan, Kanthiraj Raadhika, Sumitha Elayaperumal, Yuvaraj Sivamani, Yamunna Paramaswaran, Lim Joe Siang, Thiagharajan Venkata Rathina Kumar, Khian Giap Lim, Muthusamy Ramesh and Arunachalam Muthuraman
Curr. Issues Mol. Biol. 2025, 47(7), 518; https://doi.org/10.3390/cimb47070518 - 4 Jul 2025
Viewed by 360
Abstract
Trigeminal neuralgia is a chronic pain disorder due to neuronal damage. The present study was designed to investigate the effect of 7,8-dimethoxy coumarin (DMC) in a rat model of trigeminal neuralgia. The neuropathic pain was induced by the single endoneural injection of tumor [...] Read more.
Trigeminal neuralgia is a chronic pain disorder due to neuronal damage. The present study was designed to investigate the effect of 7,8-dimethoxy coumarin (DMC) in a rat model of trigeminal neuralgia. The neuropathic pain was induced by the single endoneural injection of tumor necrosis factor-alpha (TNF-α; 0.1 μL: stock 10 pg/mL) in the rat trigeminal nerve. The DMC (100 and 200 mg/kg) and carbamazepine (100 mg/kg) were administered orally for 10 consecutive days from the 5th day of TNF-α injection. The battery of behavioral tests, i.e., acetone drop and Von Frey filament test, was performed to assess the degree of thermal and mechanical allodynia on 0, 1st, 7th, and 14th days. In addition, the biochemical tests, i.e., total protein, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and TNF-α, were also performed in trigeminal nerve tissue. Furthermore, TNF-α-induced neuronal histopathological changes were also evaluated by the eosin and hematoxylin staining method. The administration of DMC was shown to demonstrate the significant (p < 0.05) reversal of TNF-α-induced percentage reduction of thermal and mechanical sensitivity, along with a rise in TBARS and TNF-α and a decrease in GSH levels. Further, DMC also attenuates the histopathological changes. It may be concluded that DMC may be a potential therapeutic agent for the management of trigeminal neuralgia disorders. Full article
(This article belongs to the Section Molecular Pharmacology)
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17 pages, 1350 KiB  
Review
Emerging Therapeutic Strategies Targeting GPX4-Mediated Ferroptosis in Head and Neck Cancer
by Jaewang Lee, Youngin Seo and Jong-Lyel Roh
Int. J. Mol. Sci. 2025, 26(13), 6452; https://doi.org/10.3390/ijms26136452 - 4 Jul 2025
Viewed by 662
Abstract
Ferroptosis, a regulated form of iron-dependent lipid peroxidation-induced cell death, has emerged as a compelling therapeutic strategy to overcome treatment resistance in head and neck cancer (HNC). Glutathione peroxidase 4 (GPX4), a selenoenzyme responsible for detoxifying phospholipid hydroperoxides, plays a central role in [...] Read more.
Ferroptosis, a regulated form of iron-dependent lipid peroxidation-induced cell death, has emerged as a compelling therapeutic strategy to overcome treatment resistance in head and neck cancer (HNC). Glutathione peroxidase 4 (GPX4), a selenoenzyme responsible for detoxifying phospholipid hydroperoxides, plays a central role in blocking ferroptosis and is frequently upregulated in therapy-resistant HNC subtypes. In this review, we examine the multifaceted regulation of GPX4 expression and function, including transcriptional, post-transcriptional, epigenetic, and proteostatic mechanisms. We explore how GPX4 suppression through pharmacologic inhibitors (e.g., RSL3, withaferin A, statins), metabolic stress, or combined therapies (e.g., radiotherapy, EGFR inhibitors, immunotherapy) induces ferroptosis and resensitizes resistant tumors. We also summarize emerging biomarkers, including GPX4, ACSL4, SLC7A11, and NCOA4, that predict ferroptosis sensitivity and may guide patient selection for ferroptosis-targeted therapies. Single-cell and spatial transcriptomics reveal significant intratumoral heterogeneity in ferroptosis susceptibility, underscoring the need for precision approaches. Despite promising preclinical data, challenges such as drug delivery, toxicity, and resistance mechanisms remain. Nevertheless, the ferroptosis-GPX4 axis represents a unique vulnerability in HNC that can be therapeutically exploited. Integrating ferroptosis modulation into personalized oncology may transform outcomes for patients with refractory disease. Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
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