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18 pages, 2436 KiB  
Article
Leveraging IGOOSE-XGBoost for the Early Detection of Subclinical Mastitis in Dairy Cows
by Rui Guo and Yongqiang Dai
Appl. Sci. 2025, 15(15), 8763; https://doi.org/10.3390/app15158763 (registering DOI) - 7 Aug 2025
Abstract
Subclinical mastitis in dairy cows poses a significant challenge to the dairy industry, leading to reduced milk yield, altered milk composition, compromised animal health, and substantial economic losses for dairy farmers. A model based on the XGBoost algorithm, optimized with an Improved GOOSE [...] Read more.
Subclinical mastitis in dairy cows poses a significant challenge to the dairy industry, leading to reduced milk yield, altered milk composition, compromised animal health, and substantial economic losses for dairy farmers. A model based on the XGBoost algorithm, optimized with an Improved GOOSE Optimization Algorithm (IGOOSE), is presented in this work as an innovative approach for predicting subclinical mastitis in order to overcome these problems. The Dairy Herd Improvement (DHI) records of 4154 cows served as the model’s original foundation. A total of 3232 samples with 21 characteristics made up the final dataset, following extensive data cleaning and preprocessing. To overcome the shortcomings of the original GOOSE algorithm in intricate, high-dimensional problem spaces, three significant enhancements were made. First, an elite inverse strategy was implemented to improve population initialization, enhancing the algorithm’s balance between global exploration and local exploitation. Second, an adaptive nonlinear control factor was added to increase the algorithm’s stability and convergence speed. Lastly, a golden sine strategy was adopted to reduce the risk of premature convergence to suboptimal solutions. According to experimental results, the IGOOSE-XGBoost model works better than other models in predicting subclinical mastitis, especially when it comes to recognizing somatic cell scores, which are important markers of the illness. This study provides a strong predictive framework for managing the health of dairy cows, allowing for the prompt identification and treatment of subclinical mastitis, which enhances the efficiency and quality of milk supply. Full article
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16 pages, 611 KiB  
Article
Effects of Increasing Dietary Inclusion of White Lupin on Growth Performance, Meat Quality, and Fatty Acid Profile on Growing-Fattening Pigs
by Georgeta Ciurescu, Mihaela Dumitru, Nicoleta Aurelia Lefter and Dan-Traian Râmbu
Agriculture 2025, 15(15), 1709; https://doi.org/10.3390/agriculture15151709 (registering DOI) - 7 Aug 2025
Abstract
This study investigated the possibility of partial replacement of genetically modified soybean meal (SBM) with raw white lupin (WL) seeds in growing pigs’ diets and determined its impact on performance [body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI)], [...] Read more.
This study investigated the possibility of partial replacement of genetically modified soybean meal (SBM) with raw white lupin (WL) seeds in growing pigs’ diets and determined its impact on performance [body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI)], meat quality, and fatty acid profile (FA). A total of 54 male crossbred pigs [(Topigs Large White × Norsvin Landrace) × Duroc], aged 12 weeks, with an initial average BW of 30.30 ± 0.77 kg, were divided into three dietary groups of 18 piglets each. The control group (CON) was fed a standardized SBM-based complete feed. In the experimental groups (WL1 and WL2) the SBM was replaced with increasing levels of WL seeds [WL1-5.0% and WL2-10.0% (grower period, 30–60 kg BW), and WL1-7.0% and WL2-14.0% (finisher period, 61–110 kg BW)]. All diets were formulated to be isocaloric and isonitrogenous with similar content of total lysine and sulphur amino acids, calcium, and available phosphorus. At the end of 83 days’ fattening trial, the animals were slaughtered. Longissimus dorsi muscle (LD) was sampled for analyses of the physicochemical traits. The results show that increasing the dietary raw WL concentration decreased final BW (p = 0.039), ADG (p < 0.0001), and ADFI (p = 0.004) throughout the experimental period, especially in the second phase of feeding. Dietary treatments did not affect the pigs’ blood biochemical constituents. Concerning LD muscle characteristics, the redness color (a*) and collagen content was higher (p < 0.0001) in the WL1/WL2 vs. CON group. Beneficial decrease in the values of some textural attributes (hardness, gumminess, chewiness, and resilience) of LD in the WL1/WL2 vs. CON group was registered. The use of WL had a significant effect on the content of FAs, especially for eicosapentaenoic (p = 0.014) and n-3 PUFA (p = 0.045), which were higher than those fed the CON diet. In conclusion, WL could be used as a replacement of SBM in growing–finishing pigs’ diets, with significant improvements in the meat fatty acid profile and technological properties. Full article
18 pages, 1861 KiB  
Article
Clay Nanomaterials Sorbents for Cleaner Water: A Sustainable Application for the Mining Industry
by María Molina-Fernández, Albert Santos Silva, Rodrigo Prado Feitosa, Edson C. Silva-Filho, Josy A. Osajima, Santiago Medina-Carrasco and María del Mar Orta Cuevas
Nanomaterials 2025, 15(15), 1211; https://doi.org/10.3390/nano15151211 (registering DOI) - 7 Aug 2025
Abstract
The increasing shortage of drinking water, driven by reduced rainfall and the intensification of industrial and agricultural activities, has raised justified concerns about the quantity and quality of available water resources. These sectors not only demand high water consumption but also discharge large [...] Read more.
The increasing shortage of drinking water, driven by reduced rainfall and the intensification of industrial and agricultural activities, has raised justified concerns about the quantity and quality of available water resources. These sectors not only demand high water consumption but also discharge large amounts of toxic substances such as organic matter, metal ions and inorganic anions, posing risks to both public health and the environment. This study evaluated the effectiveness of clay-based nanomaterials in the treatment of contaminated industrial wastewater from the mining sector. The materials tested included montmorillonite, high-loading expandable synthetic mica, and their organically functionalized forms (MMT, Mica-Na-4, C18-MMT, and C18-Mica-4). The experimental results show that these clays had minimal impact on the pH of the water, while a notable decrease in the chemical oxygen demand (COD) was observed. Ion chromatography indicated an increase in nitrogen and sulfur compounds with higher oxidation states. Inductively coupled plasma analysis revealed a significant reduction in the calcium concentration and an increase in the sodium concentration, likely due to cation exchange mechanisms. However, the removal of copper and iron was ineffective, possibly due to competitive interactions with other cations in the solution. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the structural modifications and interlayer spacing changes in the clay materials upon exposure to contaminated water. These findings demonstrate the potential of clay minerals as effective and low-cost materials for the remediation of industrial wastewater. Full article
(This article belongs to the Special Issue Eco-Friendly Nanomaterials: Innovations in Sustainable Applications)
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20 pages, 3448 KiB  
Article
Fatty Acid-Rich Fraction of Hibiscus syriacus L. Alleviates Atopic Dermatitis-like Skin Lesions Mouse Model via Inflammatory Pathway Modulation: Integrative Docking and Experimental Validation
by Trang Thi Minh Nguyen, Bom Park, Xiangji Jin, Qiwen Zheng, Gyeong-Seon Yi, Su-Jin Yang and Tae-Hoo Yi
Plants 2025, 14(15), 2447; https://doi.org/10.3390/plants14152447 - 7 Aug 2025
Abstract
Atopic dermatitis (AD) remains a therapeutic challenge due to the limitations of current treatments, creating demand for safer multi-target alternatives to corticosteroids. Our integrated study establishes Hibiscus syriacus L. (H. syriacus) as a mechanistically validated solution through computational and biological validation. [...] Read more.
Atopic dermatitis (AD) remains a therapeutic challenge due to the limitations of current treatments, creating demand for safer multi-target alternatives to corticosteroids. Our integrated study establishes Hibiscus syriacus L. (H. syriacus) as a mechanistically validated solution through computational and biological validation. The fraction’s two main compounds, linoleic acid and palmitic acid, exhibit favorable drug-like properties including high lipophilicity (LogP 5.2) and 87% oral absorption. Molecular docking collectively predicts comprehensive NF-κB pathway blockade. Experimental validation showed that the fraction (100 μg/mL) inhibited LPS-induced nitric oxide (NO) by 78% and TNF-α/IFN-γ-induced reactive oxygen species (ROS) by 40%, while significantly downregulating the chemokines TARC (73%) and MDC (71%). In DNCB-induced AD mice, the treatment (200 mg/kg/day) produced a 62% improvement in clinical severity scores, reduced serum IgE by 27%, decreased transepidermal water loss by 36%, and doubled skin hydration while normalizing pH levels from the alkaline to physiological range. While both treatments reduced DNCB-induced epidermal hyperplasia, H. syriacus (62.9% reduction) restored the normal thickness without pathological thinning, a critical advantage over corticosteroids that cause atrophy. This dual-action therapeutic achieves corticosteroid-level anti-inflammatory effects while restoring skin barrier integrity to normal levels and avoiding corticosteroid-associated atrophy, positioning it as a next-generation AD treatment. Full article
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26 pages, 2011 KiB  
Review
Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker
by Liliana Rebolledo-Pérez, Jorge Hernández-Bello, Alicia Martínez-Ramos, Rolando Castañeda-Arellano, David Fernández-Quezada, Flavio Sandoval-García and Irene Guadalupe Aguilar-García
Int. J. Mol. Sci. 2025, 26(15), 7638; https://doi.org/10.3390/ijms26157638 - 7 Aug 2025
Abstract
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases [...] Read more.
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use. Full article
(This article belongs to the Special Issue Neurobiological Mechanisms of Addictive Disorders)
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12 pages, 1664 KiB  
Article
Dual Effect of 4-Methylumbelliferone on INS1E Cells: Enhancing Migration and Glucose-Stimulated Insulin Secretion
by Giorgia Adamo, Daniele Romancino, Paola Gargano, Marta Sarullo, Aldo Nicosia, Sabrina Picciotto, Giulia Smeraldi, Antonella Bongiovanni and Monica Salamone
Int. J. Mol. Sci. 2025, 26(15), 7637; https://doi.org/10.3390/ijms26157637 - 7 Aug 2025
Abstract
Recent studies have demonstrated that the coumarin derivative 4-Methylumbelliferone (4MU) has an antidiabetic effect in rodent models. 4MU is known to decrease the availability of hyaluronan (HA) substrates and inhibit the activity of different HA synthases. Nevertheless, it has been observed that 4MU [...] Read more.
Recent studies have demonstrated that the coumarin derivative 4-Methylumbelliferone (4MU) has an antidiabetic effect in rodent models. 4MU is known to decrease the availability of hyaluronan (HA) substrates and inhibit the activity of different HA synthases. Nevertheless, it has been observed that 4MU may also affect cellular metabolism. In this study, we utilize the rat insulinoma beta cell line (INS-1E) cultured in both two-dimensional (2D) and three-dimensional (3D) experimental settings (pseudo islets), as an in vitro model to study beta cell functionality. For the first time, we observed that treating INS1E cells with 4MU results in improved insulin secretion. Additionally, we discovered that 4MU treatment elicited morphological changes from multilayer to monolayer conditions, along with a varied distribution of insulin granules and cell adhesion properties. Notably, we found that insulin secretion is not correlated with HA production. The same result was observed in co-culture experiments involving INS-1E cells and stromal vascular fraction (SVF) from adipose tissue. These experiments aim to investigate the effects of 4MU on beta cells in the context of its potential use in early-stage type 1 diabetes and in enhancing islet transplantation outcomes. Full article
(This article belongs to the Special Issue New Insights into Hyaluronan in Human Medicine)
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17 pages, 5085 KiB  
Article
A Segmentation Network with Two Distinct Attention Modules for the Segmentation of Multiple Renal Structures in Ultrasound Images
by Youhe Zuo, Jing Li and Jing Tian
Diagnostics 2025, 15(15), 1978; https://doi.org/10.3390/diagnostics15151978 - 7 Aug 2025
Abstract
Background/Objectives: Ultrasound imaging is widely employed to assess kidney health and diagnose renal diseases. Accurate segmentation of renal structures in ultrasound images plays a critical role in the diagnosis and treatment of related kidney diseases. However, challenges such as speckle noise and [...] Read more.
Background/Objectives: Ultrasound imaging is widely employed to assess kidney health and diagnose renal diseases. Accurate segmentation of renal structures in ultrasound images plays a critical role in the diagnosis and treatment of related kidney diseases. However, challenges such as speckle noise and low contrast still hinder precise segmentation. Methods: In this work, we propose an encoder–decoder architecture, named MAT-UNet, which incorporates two distinct attention mechanisms to enhance segmentation accuracy. Specifically, the multi-convolution pixel-wise attention module utilizes the pixel-wise attention to enable the network to focus more effectively on important features at each stage. Furthermore, the triple-branch multi-head self-attention mechanism leverages the different convolution layers to obtain diverse receptive fields, capture global contextual information, compensate for the local receptive field limitations of convolution operations, and boost the segmentation performance. We evaluate the segmentation performance of the proposed MAT-UNet using the Open Kidney US Data Set (OKUD). Results: For renal capsule segmentation, MAT-UNet achieves a Dice Similarity Coefficient (DSC) of 93.83%, a 95% Hausdorff Distance (HD95) of 32.02 mm, an Average Surface Distance (ASD) of 9.80 mm, and an Intersection over Union (IOU) of 88.74%. Additionally, MAT-UNet achieves a DSC of 84.34%, HD95 of 35.79 mm, ASD of 11.17 mm, and IOU of 74.26% for central echo complex segmentation; a DSC of 66.34%, HD95 of 82.54 mm, ASD of 19.52 mm, and IOU of 51.78% for renal medulla segmentation; and a DSC of 58.93%, HD95 of 107.02 mm, ASD of 21.69 mm, and IOU of 43.61% for renal cortex segmentation. Conclusions: The experimental results demonstrate that our proposed MAT-UNet achieves superior performance in multiple renal structure segmentation in ultrasound images. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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18 pages, 3212 KiB  
Article
Supplementation with Live and Heat-Treated Lacticaseibacillus paracasei NB23 Enhances Endurance and Attenuates Exercise-Induced Fatigue in Mice
by Mon-Chien Lee, Ting-Yin Cheng, Ping-Jui Lin, Ting-Chun Lin, Chia-Hsuan Chou, Chao-Yuan Chen and Chi-Chang Huang
Nutrients 2025, 17(15), 2568; https://doi.org/10.3390/nu17152568 - 7 Aug 2025
Abstract
Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate [...] Read more.
Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate clearance of fatigue-associated by-products. Objective: This study aimed to determine whether live or heat-inactivated Lacticaseibacillus paracasei NB23 can enhance exercise endurance and attenuate fatigue biomarkers in a murine model. Methods: Forty male Institute of Cancer Research (ICR) mice were randomized into four groups (n = 10 each) receiving daily gavage for six weeks with vehicle, heat-killed NB23 (3 × 1010 cells/mouse/day), low-dose live NB23 (1 × 1010 CFU/mouse/day), or high-dose live NB23 (3 × 1010 CFU/mouse/day). Forelimb grip strength and weight-loaded swim-to-exhaustion tests assessed performance. Blood was collected post-exercise to measure serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase (CK). Liver and muscle glycogen content was also quantified, and safety was confirmed by clinical-chemistry panels and histological examination. Results: NB23 treatment produced dose-dependent improvements in grip strength (p < 0.01) and swim endurance (p < 0.001). All NB23 groups exhibited significant reductions in post-exercise lactate (p < 0.0001), ammonia (p < 0.001), BUN (p < 0.001), and CK (p < 0.0001). Hepatic and muscle glycogen stores rose by 41–59% and 65–142%, respectively (p < 0.001). No changes in food or water intake, serum clinical-chemistry parameters, or tissue histology were observed. Conclusions: Our findings suggest that both live and heat-treated L. paracasei NB23 may contribute to improved endurance performance, increased energy reserves, and faster clearance of fatigue-related metabolites in our experimental model. However, these results should be interpreted cautiously given the exploratory nature and limitations of our study. Full article
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25 pages, 1677 KiB  
Review
Sustainable, Targeted, and Cost-Effective Laccase-Based Bioremediation Technologies for Antibiotic Residues in the Ecosystem: A Comprehensive Review
by Rinat Ezra, Gulamnabi Vanti and Segula Masaphy
Biomolecules 2025, 15(8), 1138; https://doi.org/10.3390/biom15081138 - 7 Aug 2025
Abstract
Widespread antibiotic residues are accumulating in the environment, potentially causing adverse effects for humans, animals, and the ecosystem, including an increase in antibiotic-resistant bacteria, resulting in worldwide concern. There are various commonly used physical, chemical, and biological treatments for the degradation of antibiotics. [...] Read more.
Widespread antibiotic residues are accumulating in the environment, potentially causing adverse effects for humans, animals, and the ecosystem, including an increase in antibiotic-resistant bacteria, resulting in worldwide concern. There are various commonly used physical, chemical, and biological treatments for the degradation of antibiotics. However, the elimination of toxic end products generated by physicochemical methods and the need for industrial applications pose significant challenges. Hence, environmentally sustainable, green, and readily available approaches for the transformation and degradation of these antibiotic compounds are being sought. Herein, we review the impact of sustainable fungal laccase-based bioremediation strategies. Fungal laccase enzyme is considered one of the most active enzymes for biotransformation and biodegradation of antibiotic residue in vitro. For industrial applications, the low laccase yields in natural and genetically modified hosts may constitute a bottleneck. Methods to screen for high-laccase-producing sources, optimizing cultivation conditions, and identifying key genes and metabolites involved in extracellular laccase activity are reviewed. These include advanced transcriptomics, proteomics, and metagenomics technologies, as well as diverse laccase-immobilization technologies with different inert carrier/support materials improving enzyme performance whilst shifting from experimental assays to in situ monitoring of residual toxicity. Still, more basic and applied research on laccase-mediated bioremediation of pharmaceuticals, especially antibiotics that are recalcitrant and prevalent, is needed. Full article
(This article belongs to the Special Issue Recent Advances in Laccases and Laccase-Based Bioproducts)
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17 pages, 10110 KiB  
Article
An Integrated Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation Study to Investigate the Potential Mechanism of Isoliquiritigenin in the Treatment of Ischemic Stroke
by Hang Yuan, Yuting Hou, Yuan Jiao, Xin Lu and Liang Liu
Curr. Issues Mol. Biol. 2025, 47(8), 627; https://doi.org/10.3390/cimb47080627 - 6 Aug 2025
Abstract
Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used [...] Read more.
Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used to predict potential targets related to the anti-IS effect of ISL. The binding ability of ISL to potential core targets was further analyzed by molecular docking and molecular dynamics (MD) simulations. By establishing an oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cell model, the anti-IS mechanisms of ISL were investigated via RT-qPCR and Western Blot (WB). As a result, network pharmacology analysis revealed that APP, ESR1, MAO-A, PTGS2, and EGFR may be potential core targets of ISL for anti-IS treatment. Molecular docking and molecular dynamics simulation results revealed that ISL can stably bind to the five potential core targets and form stable complex systems with them. The results of the cell experiments revealed a significant anti-IS effect of ISL. Additionally, mRNA and protein expression levels of APP, MAO-A and PTGS2 or ESR1 in the ISL treatment group were significantly lower or higher than those in the OGD/R group In conclusion, ISL may improve IS by regulating the protein expression levels of APP, ESR1, MAO-A, and PTGS2. Full article
(This article belongs to the Special Issue Cerebrovascular Diseases: From Pathogenesis to Treatment)
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14 pages, 3011 KiB  
Article
Ameliorative Effects of Soybean Powder Fermented by Bacillus subtilis on Constipation Induced by Loperamide in Rats
by Gi Soo Lee, Su Kang Kim, Ju Yeon Ban and Chung-Hun Oh
Int. J. Mol. Sci. 2025, 26(15), 7615; https://doi.org/10.3390/ijms26157615 - 6 Aug 2025
Abstract
Constipation is a prevalent gastrointestinal disorder that significantly impairs quality of life. While pharmacological agents such as loperamide are widely used to induce constipation in experimental models, there is increasing interest in natural alternatives for alleviating intestinal dysfunction. In this study, we investigated [...] Read more.
Constipation is a prevalent gastrointestinal disorder that significantly impairs quality of life. While pharmacological agents such as loperamide are widely used to induce constipation in experimental models, there is increasing interest in natural alternatives for alleviating intestinal dysfunction. In this study, we investigated the laxative effects of soybean powder fermented by Bacillus subtilis DKU_09 in a loperamide-induced rat model of constipation. The probiotic strain was isolated from cheonggukjang, a traditional Korean fermented soybean paste, and its identity was confirmed through 16S rRNA sequencing. Fermented soybean powder was characterized morphologically via scanning electron microscopy and chemically via HPLC to assess its isoflavone content. Rats were administered loperamide (5 mg/kg) for four days to induce constipation and were then treated with fermented soybean powder at doses of 100, 200, or 300 mg/kg. No pharmacological laxatives (e.g., PEG) were used as a positive control; instead, values from the treatment groups were compared with those from the loperamide-only constipation group. Key outcomes of fecal output, water content, colonic fecal retention, and gastrointestinal transit ratio were measured. The fermented product significantly improved stool frequency and moisture content, reduced colonic fecal retention, and restored gastrointestinal transit in a dose-dependent manner. Notably, the 300 mg/kg group demonstrated nearly complete recovery of fecal parameters without affecting body weight. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. These findings suggest that Bacillus subtilis-fermented soybean powder exerts synergistic laxative effects through the combined action of probiotic viability and fermentation-enhanced bioactive compounds such as aglycone isoflavones. This study supports the potential use of fermented soybean-based nutraceuticals as a natural and safe intervention for constipation and gastrointestinal dysregulation. Full article
(This article belongs to the Special Issue Functions and Applications of Natural Products)
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18 pages, 3229 KiB  
Article
AMPK-Targeting Effects of (−)-Epicatechin Gallate from Hibiscus sabdariffa Linne Leaves on Dual Modulation of Hepatic Lipid Accumulation and Glycogen Synthesis in an In Vitro Oleic Acid Model
by Hui-Hsuan Lin, Pei-Tzu Wu, Yu-Hsuan Liang, Ming-Shih Lee and Jing-Hsien Chen
Int. J. Mol. Sci. 2025, 26(15), 7612; https://doi.org/10.3390/ijms26157612 - 6 Aug 2025
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant (p < 0.01) decrease in oxidative stress by 83%, and a marked (p < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes. Full article
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18 pages, 2476 KiB  
Article
Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway
by Tsung-Hsun Hsieh, Jar-Yi Ho, Chih-Chien Wang, Feng-Cheng Liu, Chian-Her Lee, Herng-Sheng Lee and Yi-Jen Peng
Cells 2025, 14(15), 1208; https://doi.org/10.3390/cells14151208 - 6 Aug 2025
Abstract
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. [...] Read more.
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article
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16 pages, 858 KiB  
Review
Unraveling the Core of Endometriosis: The Impact of Endocrine Disruptors
by Efthalia Moustakli, Anastasios Potiris, Themos Grigoriadis, Athanasios Zikopoulos, Eirini Drakaki, Ioanna Zouganeli, Charalampos Theofanakis, Angeliki Gerede, Athanasios Zachariou, Ekaterini Domali, Peter Drakakis and Sofoklis Stavros
Int. J. Mol. Sci. 2025, 26(15), 7600; https://doi.org/10.3390/ijms26157600 - 6 Aug 2025
Abstract
Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative [...] Read more.
Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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24 pages, 2540 KiB  
Article
Classification Framework for Hydrological Resources for Sustainable Hydrogen Production with a Predictive Algorithm for Optimization
by Mónica Álvarez-Manso, Gabriel Búrdalo-Salcedo and María Fernández-Raga
Hydrogen 2025, 6(3), 54; https://doi.org/10.3390/hydrogen6030054 - 6 Aug 2025
Abstract
Given the urgent need to decarbonize the global energy system, green hydrogen has emerged as a key alternative in the transition to renewables. However, its production via electrolysis demands high water quality and raises environmental concerns, particularly regarding reject water discharge. This study [...] Read more.
Given the urgent need to decarbonize the global energy system, green hydrogen has emerged as a key alternative in the transition to renewables. However, its production via electrolysis demands high water quality and raises environmental concerns, particularly regarding reject water discharge. This study employs an experimental and analytical approach to define optimal water characteristics for electrolysis, focusing on conductivity as a key parameter. A pilot water treatment plant with reverse osmosis and electrodeionization (EDI) was designed to simulate industrial-scale pretreatment. Twenty water samples from diverse natural sources (surface and groundwater) were tested, selected for geographical and geological variability. A predictive algorithm was developed and validated to estimate useful versus reject water based on input quality. Three conductivity-based categories were defined: optimal (0–410 µS/cm), moderate (411–900 µS/cm), and restricted (>900 µS/cm). Results show that water quality significantly affects process efficiency, energy use, waste generation, and operating costs. This work offers a technical and regulatory framework for assessing potential sites for green hydrogen plants, recommending avoidance of high-conductivity sources. It also underscores the current regulatory gap regarding reject water treatment, stressing the need for clear environmental guidelines to ensure project sustainability. Full article
(This article belongs to the Special Issue Advances in Hydrogen Production, Storage, and Utilization)
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