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Search Results (2,166)

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15 pages, 2923 KB  
Article
Optimal Stubble Management Strategies of Caragana tibetica for Enhancing Stress Resistance and Vegetation Restoration
by Xiaoman Yuan, Yong Gao and Yumei Liang
Plants 2025, 14(24), 3867; https://doi.org/10.3390/plants14243867 - 18 Dec 2025
Abstract
Caragana tibetica Kom. is a key constructive species in desert steppe and desert transition zones. Long-term enclosure has led to population decline and even mortality of C. tibetica, while populations outside enclosures grow well. However, the biological mechanisms underlying the continued growth [...] Read more.
Caragana tibetica Kom. is a key constructive species in desert steppe and desert transition zones. Long-term enclosure has led to population decline and even mortality of C. tibetica, while populations outside enclosures grow well. However, the biological mechanisms underlying the continued growth of C. tibetica under grazing remain unclear. Therefore, this study aimed to clarify the effects of stubble management on the photosynthetic physiology and antioxidant characteristics of C. tibetica, and to determine the optimal stubble intensity. Plants were subjected to five stubble gradients (0%, 25%, 50%, 75%, 100%). The results showed that stubble treatments caused significant changes in both photosynthetic and antioxidant traits. Interestingly, the correlations between photosynthetic and antioxidant characteristics varied with the growth season: they were positively correlated in the early growth season, but negatively correlated in the middle and late stages. Using a generalized algorithmic model, we found that stubble intensities ranging from 0.5% to 38.7% enhanced the stress resistance of C. tibetica, with 21.6% being the optimal intensity. This study demonstrates that moderate stubble management promotes the stress resistance of C. tibetica, providing important theoretical and scientific support for vegetation restoration and ecological construction in desert steppes. Full article
(This article belongs to the Collection Feature Papers in Plant Ecology)
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22 pages, 583 KB  
Review
Harnessing Nanoparticles and Nanosuspensions to Combat Powdery Mildew: A Frontier in Vegetable and Fruit Protection
by Addisie Geremew, Alemayehu Shembo and Laura Carson
J. Fungi 2025, 11(12), 896; https://doi.org/10.3390/jof11120896 - 18 Dec 2025
Abstract
Powdery mildew poses a persistent threat to global vegetable and fruit production, particularly affecting leafy crops such as lettuce, spinach, and cucurbits. Conventional control strategies including chemical fungicides, biological agents, and resistant cultivars face limitations due to resistance development, environmental toxicity, and inconsistent [...] Read more.
Powdery mildew poses a persistent threat to global vegetable and fruit production, particularly affecting leafy crops such as lettuce, spinach, and cucurbits. Conventional control strategies including chemical fungicides, biological agents, and resistant cultivars face limitations due to resistance development, environmental toxicity, and inconsistent field efficacy. This review explores the emerging role of nanotechnology, specifically nanoparticles (NPs) and nanosuspensions (NSs), in managing powdery mildew. Metallic nanoparticles and non-metallic variants demonstrate potent antifungal activity through mechanisms such as membrane disruption, reactive oxygen species (ROS) generation, and gene regulation. Encapsulated nano-fungicides and sprayable essential oils represent potential application methods that could enhance delivery precision and activate plant defense mechanisms against powdery mildew. Integrating the application of nanoparticles and nanosuspensions with smart and digital delivery systems could be a promising strategy for managing powdery mildew infestation in fruits and vegetables. Despite their potential, challenges including ecotoxicity, formulation stability, scalability, and regulatory gaps must be addressed. This review underscores the need for interdisciplinary research to advance safe, effective, and sustainable nano-enabled solutions for powdery mildew control. Full article
(This article belongs to the Section Fungi in Agriculture and Biotechnology)
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12 pages, 891 KB  
Review
Functional and Mechanistic Insights into Plant VQ Proteins in Abiotic and Biotic Stress Responses
by Lili Zhang, Yi Wang, Zhiyong Ni and Yuehua Yu
Plants 2025, 14(24), 3855; https://doi.org/10.3390/plants14243855 - 17 Dec 2025
Abstract
Valine-glutamine motif proteins (VQ), plant-specific transcriptional co-regulators harboring the conserved FxxhVQxhTG motif, play pivotal roles in coordinating plant stress adaptation through dynamic interactions with WRKY transcription factors (WRKY), mitogen-activated protein kinases (MAPKs) cascades, and hormone signaling pathways. Evolutionary analyses reveal the characteristics of [...] Read more.
Valine-glutamine motif proteins (VQ), plant-specific transcriptional co-regulators harboring the conserved FxxhVQxhTG motif, play pivotal roles in coordinating plant stress adaptation through dynamic interactions with WRKY transcription factors (WRKY), mitogen-activated protein kinases (MAPKs) cascades, and hormone signaling pathways. Evolutionary analyses reveal the characteristics of their evolutionary protection and ancient origin, with lineage-specific expansion via genome duplication events. Structurally, compact genes lacking introns and the presence of intrinsic disordered regions (IDRs) facilitate rapid stress responses and versatile protein interactions. Functionally, VQ proteins orchestrate abiotic stress tolerance (e.g., drought, salinity, temperature extremes) by modulating reactive oxygen species (ROS) homeostasis, osmotic balance, and abscisic acid/salicylic acid (ABA/SA)-mediated signaling. Concurrently, they enhance biotic stress resistance via pathogen-responsive WRKY-VQ modules that regulate defense gene expression and hormone crosstalk. Despite advances, challenges persist in deciphering post-translational modifications, tissue-specific functions, and cross-stress integration mechanisms. Harnessing CRISPR-based editing and multi-omics approaches will accelerate the exploitation of VQ genes for developing climate-resilient crops. This review synthesizes the molecular architecture, evolutionary dynamics, and multifunctional regulatory networks of VQ proteins, providing a roadmap for their utilization in sustainable agriculture. Full article
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27 pages, 6816 KB  
Article
Experimental Evaluation of the Performance of a Flat Sheet Reverse Osmosis Membrane Under Variable and Intermittent Operation Emulating a Photovoltaic-Driven Desalination System
by Evangelos Dimitriou, Dimitrios Loukatos, Konstantinos G. Arvanitis and George Papadakis
Water 2025, 17(24), 3576; https://doi.org/10.3390/w17243576 - 16 Dec 2025
Abstract
The integration of Reverse Osmosis (RO) desalination with Renewable Energy (RE) sources offers a sustainable approach to freshwater production, particularly in remote and off-grid regions. However, the variable and intermittent output of RE power can cause operational instability that affects membrane performance and [...] Read more.
The integration of Reverse Osmosis (RO) desalination with Renewable Energy (RE) sources offers a sustainable approach to freshwater production, particularly in remote and off-grid regions. However, the variable and intermittent output of RE power can cause operational instability that affects membrane performance and system reliability. This study experimentally evaluated a flat sheet seawater RO membrane under variable conditions emulating a Photovoltaic (PV)-powered system over three days. Three scenarios were examined: (i) steady full-load operation representing PV with battery storage, (ii) variable operation representing sunny-day PV output, and (iii) highly variable operation representing cloudy-day PV output. A Variable Frequency Drive (VFD) regulated by an Arduino microcontroller adjusted high-pressure pump operation in real time to replicate power fluctuations without energy storage. Each scenario operated for eight hours per day and was tested with and without end-of-day rinsing. Under the highly variable cloudy-day scenario without rinsing, water permeability decreased by 37%, salt rejection decreased by 18%, and membrane resistance increased by 37%, indicating compaction and fouling effects. Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR) confirmed structural changes in membranes exposed to fluctuating conditions. These results highlight the need for improved operational strategies to protect membrane longevity in RE-powered desalination systems. Full article
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21 pages, 37241 KB  
Article
Genome-Wide Identification of the AGC Kinase Family in Tetraploid Potato (Solanum tuberosum L.) Cultivar ‘Qingshu No. 9’ and Functional Analysis of StD6PK in Response to Late Blight (Phytophthora infestans)
by Yifan Zhou, Chunna Lv, Yihan Zhao, Yuting Bao and Fang Wang
Plants 2025, 14(24), 3818; https://doi.org/10.3390/plants14243818 - 15 Dec 2025
Viewed by 93
Abstract
The AGC kinase family is crucial for regulating plant disease resistance, integrating hormone signals, managing reactive oxygen species (ROS) metabolism, and maintaining redox balance. However, research on AGC kinases in Solanaceae plants is limited, and the functions of most AGC kinases remain unidentified. [...] Read more.
The AGC kinase family is crucial for regulating plant disease resistance, integrating hormone signals, managing reactive oxygen species (ROS) metabolism, and maintaining redox balance. However, research on AGC kinases in Solanaceae plants is limited, and the functions of most AGC kinases remain unidentified. Using the tetraploid potato (Solanum tuberosum L.) cultivar ‘Tingsha No. 9’, we conducted a genome-wide identification of the AGC gene family and profiled transcript responses to late-blight (Phytophthora infestans) stress. Additionally, we examined the subcellular localization and characterized the phenotypic responses of overexpression lines of the late-blight–responsive kinase StD6PK under late-blight stress. A total of 141 AGC family members were identified in ‘Qingshu No. 9’, categorized into eight subfamilies. This classification includes one cultivar-specific subfamily that was previously unrecognized, as well as 50 AGC family members within subfamily 1. AGC family members had significant differences in physicochemical characteristics and most of which were located in the nucleus. AGC family members are distributed on 46 chromosomes, with the largest number of chromosome 11 and the least number of chromosome 7. Gene duplication is dominated by whole-genome duplication (WGD) and segmental duplication. Ka/Ks values of all collinear pairs are less than 1. Purification selection drives family evolution in a long evolutionary process. Its promoter is rich in light-responsive, hormone-responsive, and stress-responsive elements, and its expression varies significantly in tissues; and some genes are highly expressed in specific organs. RNA-seq analysis revealed that 78.1% of the members responded to late-blight stress, and the expression levels of the selected eight subfamily members all showed significant increases or decreases after inoculation with late blight. StD6PK (Soltu.Q9.Chr04_A40011450.g) was strongly induced at 48~72 h, and its expression level at 72 h was 5.7 times higher than that at 0 h. Stable transformation of potato demonstrated that overexpression of StD6PK could enhance the resistance of potato to late blight, with subcellular localization revealing its nuclear localization characteristic. This study was the first time to complete the identification of AGC family genome of tetraploid potato ‘Qingshu No. 9’, reveal its evolution and expression characteristics, clarify the response characteristics of StD6PK to late blight, and provide insights into the evolutionary and functional basis of the AGC kinase gene family in potato late blight resistance mechanisms, while supplying genetic resources to accelerate the development of late blight-resistant germplasm. Full article
(This article belongs to the Section Plant Genetics, Genomics and Biotechnology)
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31 pages, 5359 KB  
Article
Saccharomyces cerevisiae TAD1 Mutant Strain As Potential New Antimicrobial Agent: Studies on Its Antibacterial Activity and Mechanism of Action
by Yu Zhang, Mengkun Li, Shulei Ji, Liu Cong, Shanshan Mao, Jinyue Wang, Xiao Li, Tao Zhu, Zuobin Zhu and Ying Li
Microorganisms 2025, 13(12), 2848; https://doi.org/10.3390/microorganisms13122848 - 15 Dec 2025
Viewed by 79
Abstract
Human infections caused by pathogenic bacteria remain a major global health concern. Among them, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Salmonella typhi are particularly prevalent and associated with significant morbidity and mortality. While antibiotics have long been the cornerstone [...] Read more.
Human infections caused by pathogenic bacteria remain a major global health concern. Among them, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Salmonella typhi are particularly prevalent and associated with significant morbidity and mortality. While antibiotics have long been the cornerstone of bacterial infection treatment, the widespread and often inappropriate use of these drugs has led to the emergence of multidrug-resistant (MDR) strains. This escalating resistance crisis underscores the urgent need for alternative therapeutic strategies. Amid the escalating global antimicrobial-resistance crisis, a genome-wide screen of 1800 Saccharomyces cerevisiae knockouts identified a TAD1-deficient mutant whose cell-free supernatant (CFS) rapidly eradicates multidrug-resistant E. coli, S. aureus, K. pneumoniae, and S. typhi in vitro. CFS disrupts pathogenic biofilms, downregulates biofilm-associated genes, and exerts bactericidal activity by triggering intracellular reactive oxygen species (ROS) accumulation and compromising envelope integrity. Probiotic profiling revealed robust tolerance to an acidic pH and physiological bile, high auto-aggregation, and efficient co-aggregation with target pathogens. In both Galleria mellonella and murine infectious models, administration of CFS or live yeast significantly increased survival, attenuated intestinal histopathology, and reduced inflammatory infiltration. These data establish the TAD1-knockout strain and its secreted metabolites as dual-function antimicrobial-probiotic entities, offering a sustainable therapeutic alternative to conventional antibiotics against multidrug-resistant bacterial infections. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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32 pages, 1845 KB  
Systematic Review
Relationship Between Maxillary Transverse Deficiency and Respiratory Problems: A Systematic Review of the Effectiveness of Devices over the Past Decade
by Gaetano Ierardo, Fabiana Nicita, Iole Vozza, Antonella Polimeni and Valeria Luzzi
J. Clin. Med. 2025, 14(24), 8861; https://doi.org/10.3390/jcm14248861 - 15 Dec 2025
Viewed by 84
Abstract
Background/Objectives: Maxillary transverse deficiency is linked to impaired nasal breathing and pediatric sleep-disordered breathing. This systematic review evaluated the effects of maxillary expansion (ME) on upper-airway morphology and breathing function in growing patients. Methods: The search was conducted on PubMed/MEDLINE, Scopus, [...] Read more.
Background/Objectives: Maxillary transverse deficiency is linked to impaired nasal breathing and pediatric sleep-disordered breathing. This systematic review evaluated the effects of maxillary expansion (ME) on upper-airway morphology and breathing function in growing patients. Methods: The search was conducted on PubMed/MEDLINE, Scopus, ScienceDirect, Cochrane CENTRAL, and gray literature (January 2015–April 2025). Eligible RCTs, controlled trials, and cohort/observational studies assessed airway morphology and/or respiratory outcomes after ME in pediatric/adolescent patients. Risk of bias was evaluated with RoB 2 (RCTs) and ROBINS-I (non-randomized studies). The findings were synthesized qualitatively and certainty graded with GRADE. Results: Forty-one studies were included. Imaging consistently showed enlargement of the nasal cavity and nasopharynx after expansion, whereas the effects in the oropharynx and hypopharynx, as well as in the maxillary sinuses, were smaller or variable. Objective patency improved in several studies (higher peak nasal inspiratory flow, reduced nasopharyngeal obstruction, and nasal resistance), whereas computational fluid dynamics generally showed non-significant trends toward lower resistance. Spirometry improved, particularly in oral breathers (gains in FEV1, FVC, FEF25–75%). Polysomnography indicated reductions in AHI and improved oxygenation in some pediatric OSA cohorts, although other RCTs reported null PSG effects. Caregiver-reported sleep and quality-of-life outcomes were consistently enhanced. Device design modestly influenced regional widening, but overall respiratory effects were similar across expanders. By GRADE, certainty was low for airway morphology and very low for breathing function. Conclusions: In growing patients, ME reliably enlarges upper-airway compartments, especially the nasal cavity and nasopharynx, yet functional improvements are heterogeneous. Standardized outcomes and integrated morphological–functional assessments are needed to strengthen the evidence base. Full article
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15 pages, 307 KB  
Review
Fifty Years and Counting: Searching for the “Silver Bullet” or the “Silver Shotgun” to Mitigate Preharvest Aflatoxin Contamination
by Baozhu Guo, Idrice Carther Kue Foka, Dongliang Wu, Josh P. Clevenger, Rong Di and Jake C. Fountain
Toxins 2025, 17(12), 596; https://doi.org/10.3390/toxins17120596 - 15 Dec 2025
Viewed by 111
Abstract
The year 2025 marks two significant milestones for aflatoxin research: 65 years since aflatoxin was first identified in 1960, and 50 years of focused research on preharvest aflatoxin contamination since it was first recognized in 1975. Studies in the 1970s revealed that A. [...] Read more.
The year 2025 marks two significant milestones for aflatoxin research: 65 years since aflatoxin was first identified in 1960, and 50 years of focused research on preharvest aflatoxin contamination since it was first recognized in 1975. Studies in the 1970s revealed that A. flavus could infect crops like maize and produce aflatoxin in the field before harvest and made it possible to investigate the potential genetic resistance in crops to mitigate the issues. Tremendous efforts have been made to learn about the process and regulation of aflatoxin production along with interactions between A. flavus and host plants as influenced by environmental factors. This has allowed for the breeding of more resistant crops and investigations into the underlying genetic and genomic components of resistance mechanisms in crops like maize and peanut. However, despite decades of studies, many questions remain. One established “dogma” is that drought stress, especially when combined with high temperatures, is the single greatest contributing factor to preharvest aflatoxin contamination and is a perennial risk faced throughout the major agricultural production regions of the world. Although there are many reviews summarizing the decades’ long wealth of information about A. flavus, aflatoxin biosynthesis, management and host plant resistance, there are few reports that put the spotlight on why aflatoxin contamination is exacerbated by drought stress, which places plants under severe physiological stress and weakens immune systems. Therefore, here we will focus on three major areas of research in maize: the “living embryo” theory and host resistance mechanisms, the “Key Largo hypothesis” and the causes of drought-exacerbated aflatoxin contamination, and recent advancements in CRISPR-based genome editing for enhancing drought tolerance and increasing plant immune responses. This will highlight key breakthroughs and future prospects for the continuing development of superior crop germplasm and cultivars and for mitigating aflatoxin contamination in food and feed supply chains. Full article
14 pages, 1454 KB  
Article
Slight Water Loss Combined with Methyl Jasmonate Treatment Improves Actinidia arguta Resistance to Gray Mold by Modulating Reactive Oxygen Species and Phenylpropanoid Metabolism
by Xinqi Liu, Qingxuan Wang, Feiyang Wang, Baodong Wei, Qian Zhou, Shunchang Cheng and Yang Sun
Foods 2025, 14(24), 4311; https://doi.org/10.3390/foods14244311 - 14 Dec 2025
Viewed by 156
Abstract
In this study, we aimed to elucidate the mechanism through which treatment with slight water loss combined with methyl jasmonate (MeJA) regulates gray mold development in Actinidia arguta, focusing on reactive oxygen species (ROS) and phenylpropanoid metabolism. The results showed that water [...] Read more.
In this study, we aimed to elucidate the mechanism through which treatment with slight water loss combined with methyl jasmonate (MeJA) regulates gray mold development in Actinidia arguta, focusing on reactive oxygen species (ROS) and phenylpropanoid metabolism. The results showed that water loss alone, MeJA alone, and their combination each reduced the incidence of disease, with the combined treatment showing the greatest efficacy. At the end of the storage period, the combined treatment enhanced the activities of superoxide dismutase (SOD), polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate-CoA ligase (4CL). It also increased the accumulation of defense-related substances (total phenol and lignin contents) and up-regulated AaPAL, Aa4CL, AaC4H, and AaC3′H gene expression. Furthermore, the combined treatment reduced the disease severity index from 60% to 16% and delayed onset by 2 d. In conclusion, slight water loss combined with MeJA treatment effectively suppressed gray mold. This effect may be attributed to activation of ROS metabolism, induction of phenylpropanoid metabolism, and up-regulation of related genes, which enhanced the resistance of the fruit to gray mold. Full article
(This article belongs to the Section Food Microbiology)
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24 pages, 3511 KB  
Article
An Antioxidative Exopolysaccharide–Protein Complex of Cordyceps Cs-HK1 Fungus and Its Epithelial Barrier-Protective Effects in Caco-2 Cell Culture
by Yan Yu Zhu, Margaret M. H. Wu, Zi Chen Zhao, Fang Ting Gu, Lin Xi Huang, Kevin W. H. Kwok and Jian Yong Wu
Antioxidants 2025, 14(12), 1501; https://doi.org/10.3390/antiox14121501 - 14 Dec 2025
Viewed by 217
Abstract
The exopolysaccharides (EPS) from the mycelial fermentation of Cordyceps sinensis Cs-HK1, especially the low-molecular weight, protein-rich exopolysaccharide fractions (EPS-LM), have previously exhibited significant antioxidant activity. This study further investigated the antioxidant and protective effects of EPS-LM on intestinal epithelial barrier integrity in Caco-2 [...] Read more.
The exopolysaccharides (EPS) from the mycelial fermentation of Cordyceps sinensis Cs-HK1, especially the low-molecular weight, protein-rich exopolysaccharide fractions (EPS-LM), have previously exhibited significant antioxidant activity. This study further investigated the antioxidant and protective effects of EPS-LM on intestinal epithelial barrier integrity in Caco-2 monolayers challenged with hydrogen peroxide (H2O2, 550 μM). EPS-LM contained two major molecular-weight fractions, 25 kDa and 1.7 kDa, with 19.3% total carbohydrate and 28.7% protein content (w/w). Treatment of the cells with EPS-LM (50–200 μg/mL) showed concentration-dependent protective effects against ROS-induced losses of cell viability and epithelial barrier integrity. EPS-LM treatment enhanced the activities of major antioxidant enzymes (SOD, GSH-Px, and CAT) and modulated NRF2 and its downstream target NQO1, consistent with alleviated oxidative stress. It also improved several indicators of intestinal barrier function, including increased transepithelial electrical resistance and upregulation of tight junction proteins (Occludin, ZO-1, and Claudin-1). These results provide new experimental evidence and theoretical basis for the nutraceutical potential of EPS-LM to mitigate oxidative stress and preserve intestinal epithelial barrier integrity. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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17 pages, 1461 KB  
Article
Cucurbitacin D Induces Apoptotic Cell Death via NOX4 and Overcomes Radioresistance in Colorectal Cancer
by Tae Woo Kim
Int. J. Mol. Sci. 2025, 26(24), 12022; https://doi.org/10.3390/ijms262412022 - 13 Dec 2025
Viewed by 124
Abstract
Colorectal cancer (CRC) incidence is a significant cancer globally, and radiotherapy resistance is a serious problem. Cucurbitacin D (CBD), extracted from many plants such as the tubers of Trichosanthes kirilowii and the fruits of Ecballium elaterium (squirting cucumber), has various therapeutic effects, such [...] Read more.
Colorectal cancer (CRC) incidence is a significant cancer globally, and radiotherapy resistance is a serious problem. Cucurbitacin D (CBD), extracted from many plants such as the tubers of Trichosanthes kirilowii and the fruits of Ecballium elaterium (squirting cucumber), has various therapeutic effects, such as anti-cancer, -inflammation, -diabetes, and -viral infection effects. Since reports have indicated that CBD exhibits effective anti-cancer activity across various cancer types, our hypothesis is that CBD will overcome radioresistance in CRC radiotherapy. In the present study, we identified that CBD, a triterpenoid compound isolated from Trichosanthes kirilowii and Ecballium elaterium, has an anti-cancer and anti-inflammatory effect in vivo and in vitro. In LPS-induced murine models, CBD suppresses LPS-mediated cytokines, including TNFα, IL-6, IL-1β, and COX-2. In CRC xenograft mouse models, CBD treatment results in significantly smaller tumor volumes than the control. In HCT116 and HT29 cells, CBD treatment suppresses cell viability and increases LDH cytotoxicity and caspase-3 activity and cleavage. However, combined treatment of CBD and Z-VAD-FMK inhibits caspase-dependent apoptosis and cell death. Since CBD induces intracellular calcium (Ca2+) and reactive oxygen species (ROS) generation, it mediates ER stress-induced apoptotic cell death through the PERK-ATF4-CHOP axis. Moreover, ER stress inducer thapsigargin (TG) mediates synergistic apoptotic cell death in CBD-treated HCT116 and HT29 cells. However, PERK or CHOP knockdown suppresses ER stress-mediated apoptosis in CBD-treated HCT116 and HT29 cells. CBD treatment induces oxidative stress through the NADPH Oxidase 4 (NOX4) and also increases ROS generation. However, NOX4 knockdown and ROS inhibitor NAC or DPI block ER stress-induced apoptotic cell death by inhibiting the suppression of cell viability and the elevation of caspase-3 activity, LDH cytotoxicity, and intracellular ROS activity in CBD-mediated HCT116 and HT29 cells. We established radioresistant CRC models (HCT116R and HT29R); subsequently, radiation (2 Gy) in combination with CBD treatment overcame radioresistance via the modulation of the epithelial–mesenchymal transition (EMT) phenomenon, including the increase in N-cadherin and vimentin and the reduction in E-cadherin. Thus, these results show that CBD may be a new powerful therapeutic approach for CRC radiotherapy. Full article
(This article belongs to the Special Issue New Advances in Reversing Cancer Therapy Resistance)
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35 pages, 503 KB  
Review
Oxidative Stress, Antioxidant Cofactor Micronutrients, and Cognitive Outcomes in Childhood Obesity: Mechanisms, Evidence, and Therapeutic Opportunities
by Marina Darenskaya, Karen J. Cloete, Luybov Rychkova, Sergey Kolesnikov, Zhanna Prokhorova, Natalya Semenova, Natalya Yuzvak and Lyubov Kolesnikova
Int. J. Mol. Sci. 2025, 26(24), 12012; https://doi.org/10.3390/ijms262412012 - 13 Dec 2025
Viewed by 273
Abstract
Overweight and obesity are major public health concerns among children and adolescents worldwide. The most prevalent form is exogenous–constitutional obesity, which is driven by a sedentary lifestyle and an unhealthy diet in which caloric intake exceeds energy expenditure. Beyond their association with chronic [...] Read more.
Overweight and obesity are major public health concerns among children and adolescents worldwide. The most prevalent form is exogenous–constitutional obesity, which is driven by a sedentary lifestyle and an unhealthy diet in which caloric intake exceeds energy expenditure. Beyond their association with chronic disease, these factors are closely linked to deficits in cognitive development and executive functions essential for learning (including working memory, sustained attention, planning, behavioral self-regulation, and cognitive flexibility). Oxidative stress (OS), characterized by the accumulation of reactive oxygen species (ROS) in cells and extracellular fluids, is a significant potential mediator in childhood obesity and an important contributor to its comorbidities. The antioxidant defense system (AOD)’s activity largely depends on levels of trace element cofactors, which determine the body’s resistance to adverse environmental factors (the “maladaptation phenomenon”). OS and trace element deficiencies contribute to the development of morphological changes in the brain, thus serving as a critical connecting link between childhood obesity and cognitive impairment. Non-pharmacological interventions are the most accessible and effective approach for prevention and treatment. Bioactive compounds derived from food and natural plants, classified as antioxidants and phytopreparations, may represent a promising complementary approach. These compounds are most effective when used in combination with sustained lifestyle modifications in children. Research in this area can help define future directions for study and develop targeted intervention strategies in the pediatric population. The aim of this review is to examine the relationship between OS, antioxidant cofactor micronutrients, and cognitive outcomes in childhood obesity and to explore mechanisms, evidence, and therapeutic opportunities. Full article
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20 pages, 827 KB  
Article
Exploring the Antibacterial, Anti-Inflammatory, and Antioxidant Properties of the Natural Food Supplement “Protegol” as a Supportive Strategy in Respiratory Tract Infections
by Alexia Barbarossa, Maria Pia Argentieri, Maria Valeria Diella, Eleonora Spinozzi, Filippo Maggi, Antonio Carrieri, Filomena Corbo, Antonio Rosato and Alessia Carocci
Antibiotics 2025, 14(12), 1260; https://doi.org/10.3390/antibiotics14121260 - 13 Dec 2025
Viewed by 339
Abstract
Background/Objectives: Respiratory tract infections (RTIs) remain a leading cause of morbidity worldwide and are frequently associated with the emergence of multidrug-resistant pathogens. In this context, natural compounds represent a valuable source of novel antimicrobial and immunomodulatory agents. The present study aimed to [...] Read more.
Background/Objectives: Respiratory tract infections (RTIs) remain a leading cause of morbidity worldwide and are frequently associated with the emergence of multidrug-resistant pathogens. In this context, natural compounds represent a valuable source of novel antimicrobial and immunomodulatory agents. The present study aimed to evaluate the antibacterial, anti-inflammatory, and antioxidant activities of Protegol, a natural food supplement enriched in bioactive phytochemicals including hydroalcoholic extracts of propolis and hedge mustard (Sisymbrium officinale (L.) Scop.) aerial parts, together with honey, against clinically relevant bacterial strains and in cellular models of inflammation and oxidative stress. Furthermore, the ability of the multi-herbal formulation to alter the permeability of the bacterial cell wall was assessed. Methods: The antibacterial properties of Protegol were evaluated by determining its minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) against a panel of Gram-positive and Gram-negative bacteria, using the broth microdilution method. Cell wall permeability was investigated through the propidium iodide (PI) uptake assay. The anti-inflammatory potential was investigated in LPS-stimulated RAW 264.7 macrophages by measuring nitric oxide (NO) production with the Griess assay. The antioxidant activity was evaluated in BALB/3T3 fibroblasts exposed to hydrogen peroxide, using the DCFH-DA assay. Results: Protegol exhibited a broad-spectrum antibacterial effect, with MIC values ranging from 1.5 to 6.2 mg/mL and MBC values between 3.1 and 12.4 mg/mL. The strongest activity was observed against Staphylococcus aureus and Streptococcus pyogenes, including clinical isolates, while moderate efficacy was detected against resistant Klebsiella pneumoniae strains. PI uptake assays confirmed a dose-dependent disruption of bacterial membrane integrity, supporting a direct effect of Protegol on cell wall permeability. In macrophages, Protegol significantly and dose-dependently reduced NO release, lowering production to 44% at the highest concentration tested. In BALB/3T3 cells, Protegol markedly decreased ROS accumulation to 24% at the same concentration. Conclusions: Overall, the findings support the potential of Protegol as a natural adjuvant to the conventional therapies for respiratory tract health by counteracting bacterial pathogens, reducing inflammation, and mitigating oxidative stress, thereby supporting host defense mechanisms in the context of respiratory tract infections. Full article
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22 pages, 2591 KB  
Article
Novel Adamantane–Sclareol Hybrids Exploit ROS Vulnerability to Overcome Multidrug-Resistance in Glioblastoma Cells
by Ema Lupšić, Pavle Stojković, Marija Grozdanić, Nataša Terzić-Jovanović, Milica Pajović, Fani Koutsougianni, Dimitra Alexopoulou, Igor M. Opsenica, Milica Pešić and Ana Podolski-Renić
Molecules 2025, 30(24), 4756; https://doi.org/10.3390/molecules30244756 - 12 Dec 2025
Viewed by 229
Abstract
Multidrug resistance (MDR) presents a significant challenge in the treatment of glioblastoma. We evaluated six novel adamantane–sclareol hybrids that integrate a natural labdane diterpene scaffold with an adamantane moiety to address this issue. Compounds 2, 5, and 6 demonstrated the ability [...] Read more.
Multidrug resistance (MDR) presents a significant challenge in the treatment of glioblastoma. We evaluated six novel adamantane–sclareol hybrids that integrate a natural labdane diterpene scaffold with an adamantane moiety to address this issue. Compounds 2, 5, and 6 demonstrated the ability to bypass P-glycoprotein (P-gp)-mediated resistance in resistant U87-TxR cells and induced collateral sensitivity, with compound 2 exhibiting the highest selectivity for glioblastoma compared to normal glial cells. Mechanistic studies revealed that compounds 2 and 5 selectively triggered early apoptosis in MDR cells, significantly elevated levels of H2O2 and peroxynitrite, and disrupted mitochondrial membrane potential. Additionally, these compounds altered the expression of key genes involved in glutathione (GSH) and thioredoxin (Trx) antioxidant defense systems and increased ASK1 protein levels, indicating the activation of ROS-driven apoptotic signaling. Both compounds inhibited P-gp function, leading to enhanced intracellular accumulation of rhodamine 123 (Rho 123) and synergistically sensitized U87-TxR cells to paclitaxel (PTX). A preliminary Rag1 xenograft study demonstrated that compound 5 effectively suppressed tumor growth without causing significant weight loss. Collectively, these findings position adamantane–sclareol hybrids, particularly compounds 2 and 5, as promising strategies that exploit an MDR-associated reactive oxygen species (ROS) vulnerability, combining selective cytotoxicity, redox disruption, and P-gp modulation to eliminate resistant glioblastoma cells and enhance the efficacy of chemotherapeutics. Full article
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Review
Oxidative Stress in Liver Metabolic Dysfunction and Diseases, with a Focus on Hepatogenic Diabetes: Effect of Alcohol Consumption
by Martha Lucinda Contreras-Zentella, Lorena Carmina Hernández-Espinosa and Rolando Hernández-Muñoz
Antioxidants 2025, 14(12), 1494; https://doi.org/10.3390/antiox14121494 - 12 Dec 2025
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Abstract
Metabolic dysfunction–associated fatty liver disease (MASLD) is associated with severe forms of liver injury, including fibrosis and cirrhosis. The main risk factors for MASLD—obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, and insulin resistance (IR)—contribute to metabolic disturbances that initiate hepatic steatosis. Metabolic and [...] Read more.
Metabolic dysfunction–associated fatty liver disease (MASLD) is associated with severe forms of liver injury, including fibrosis and cirrhosis. The main risk factors for MASLD—obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, and insulin resistance (IR)—contribute to metabolic disturbances that initiate hepatic steatosis. Metabolic and alcohol-related liver disease (MetALD) describes patients with MASLD who also present alcohol-associated hepatic injury. Chronic oxidative and inflammatory stress promotes the progression of steatosis in both conditions. T2DM and chronic alcohol consumption are independent lifestyle-related risk factors for cirrhosis within the spectrum of metabolic dysfunction–related liver disease (MASLD and MetALD). The coexistence of both conditions may exacerbate hepatic pathological alterations. IR, which is frequently observed in patients with cirrhosis, can lead to the development of a condition known as hepatogenic diabetes (HD). HD is characterized by hyperinsulinemia, IR, and β-cell dysfunction occurring during the onset of cirrhosis and is associated with hepatic inflammation even in the absence of traditional metabolic risk factors such as obesity or a prior history of T2DM. In this context, alcohol intake enhances lipolysis in peripheral tissues, promotes hepatic steatosis, and aggravates metabolic dysfunction, ultimately contributing to excessive mitochondrial production of reactive oxygen species (ROS). Therefore, the present review examines the role of oxidative stress—both alcohol-related and non-alcohol–related—in the pathogenesis of HD, with particular emphasis on ethanol metabolism, oxidative stress, and their interactions in conditions such as T2DM and MetALD. Full article
(This article belongs to the Special Issue Alcohol-Induced Oxidative Stress in Health and Disease, 2nd Edition)
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