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23 pages, 10270 KB  
Article
Polystyrene Nanoplastics Induce Early Mitochondrial Dysfunction in H9c2 Cardiomyoblasts Without Substantial Cell Damage
by Ming-Hung Shen, Pei-Hsuan Lu, Ting-Yu Tsai, Eddy Owaga, Yi-Sheng Tsai, Chia-Wen Chen and Rong-Hong Hsieh
Antioxidants 2026, 15(7), 801; https://doi.org/10.3390/antiox15070801 (registering DOI) - 26 Jun 2026
Viewed by 147
Abstract
Global plastic production has led to widespread contamination by micro- and nanoplastics, with polystyrene nanoplastics (PSNPs) increasingly being detected in human biological samples, including blood and cardiac tissue. Given the critical role of mitochondria in cardiac energy metabolism, this study investigated whether 100 [...] Read more.
Global plastic production has led to widespread contamination by micro- and nanoplastics, with polystyrene nanoplastics (PSNPs) increasingly being detected in human biological samples, including blood and cardiac tissue. Given the critical role of mitochondria in cardiac energy metabolism, this study investigated whether 100 nm PSNPs interact with mitochondria and affect mitochondrial function in H9c2 cardiomyoblasts. Cellular uptake and intracellular distribution were examined, followed by an evaluation of mitochondrial ultrastructure, intracellular and mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential, mitochondrial dynamics and mitophagy-related gene expression, mitochondrial DNA copy number, and metabolic function. PSNPs were internalized but did not directly localize to mitochondria within 24 h. No significant cytotoxicity, increase in intracellular or mitochondrial ROS production, or alteration in basal metabolic activity was observed. However, PSNP exposure resulted in intracellular accumulation, an altered mitochondrial ultrastructure characterized by crista loosening and vacuole-like structural changes. These changes were accompanied by reduced mitochondrial membrane potential; the upregulation of mitochondrial dynamics-related genes, including optic atrophy 1 (Opa1) and dynamin-related protein 1 (Drp1); the suppression of PTEN-induced kinase 1 (PINK1)/Parkin RBR E3 ubiquitin protein ligase (Parkin)-mediated mitophagy-related genes; and decreased maximal respiratory capacity. Lactate production and the extracellular acidification rate remained unchanged, suggesting that compensatory glycolysis was not activated. These findings indicate that PSNP exposure induces early mitochondrial structural and functional alterations without substantial cell damage, suggesting a potential reduction in cardiac adaptive capacity under PSNP-induced stress conditions. Full article
(This article belongs to the Special Issue Oxidative Stress Induced by Micro(Nano)plastics)
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16 pages, 6271 KB  
Article
Effect of Letrozole Administration on Reproductive Performance and Plasma Metabolites of Ewes During Estrus Synchronization Treatment
by Tingting Li, Xihu Wang, Hao Lu, Tingting Lu, Reyimu Reyilaguli, Haibo Lv, Xiaojun Liu, Jianjun Zhang, Shijie Li, Rui Xiao and Guodong Zhao
Life 2026, 16(7), 1058; https://doi.org/10.3390/life16071058 - 25 Jun 2026
Viewed by 152
Abstract
This study investigated the effects of letrozole (LE) on reproductive performance, hormones, and plasma metabolites in Turpan Black ewes. Sixty-six multiparous non-pregnant ewes were randomly assigned to a Control group or an LE group (0.2 mg/kg body weight, added to the basal diet) [...] Read more.
This study investigated the effects of letrozole (LE) on reproductive performance, hormones, and plasma metabolites in Turpan Black ewes. Sixty-six multiparous non-pregnant ewes were randomly assigned to a Control group or an LE group (0.2 mg/kg body weight, added to the basal diet) for 180 days, both receiving estrus synchronization. LE significantly increased the twinning rate (p < 0.05), but no significant differences were observed in estrus rate, conception rate, or lambing rate (p > 0.05). Hormone analysis revealed significant changes in Luteinizing Hormone (LH), Progesterone (P4) (group, time, and interaction effects), Estradiol (E2), Testosterone (T) (time effect), Gonadotropin-Releasing Hormone (GnRH) (group and interaction effects), and Follicle-Stimulating Hormone (FSH) (primarily time effect). Metabolomic analysis identified 3451 differential metabolites. L-saccharopine and 5-hydroxylysine were downregulated (p < 0.01), and estrone was decreased (p < 0.05). Lysylhistidine was upregulated (p < 0.05), while testosterone and LE showed rising trends without statistical significance (p > 0.05). These metabolites were mainly enriched in amino acid metabolism and lipid metabolism pathways related to reproduction. Significant correlations were also detected between several metabolites and reproductive hormones. LE improves the twinning rate in Turpan Black ewes, likely by modulating key reproductive hormones (LH, P4, GnRH, FSH, E2, T) and altering plasma metabolites involved in amino acid and lipid metabolism. These findings provide new insights into the regulatory mechanisms of letrozole on ovine reproduction. Full article
(This article belongs to the Special Issue Gut Health and Nutritional Strategies in Animals)
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20 pages, 19179 KB  
Article
Split Potassium Fertilization Modulates Endogenous Hormone Homeostasis to Optimize the Grain-Filling Process and Mitigate High-Temperature Damage in Rice
by Xinyue Zhang, Junjie Dong, Youfa Li, Yuanze Sun and Haowei Fu
Plants 2026, 15(12), 1781; https://doi.org/10.3390/plants15121781 - 9 Jun 2026
Viewed by 224
Abstract
High temperature during flowering and grain filling severely reduces rice yield and grain quality. Split potassium (K) fertilization can mitigate such heat-induced damage, yet its mechanisms linking grain filling, endogenous hormones and grain performance remain unclear. Here, a two-year pot experiment was conducted [...] Read more.
High temperature during flowering and grain filling severely reduces rice yield and grain quality. Split potassium (K) fertilization can mitigate such heat-induced damage, yet its mechanisms linking grain filling, endogenous hormones and grain performance remain unclear. Here, a two-year pot experiment was conducted to explore the effects of split K application on rice yield, quality and hormonal metabolism under high temperature. Four treatments included ambient temperature with full basal K (AT-K100), high temperature with full basal K (HT-K100), and two split K regimes under high temperature (HT-K70+30, HT-K30+70). Split K application decreased abscisic acid (ABA) levels at 5 days after anthesis (DAA), increased indole-3-acetic acid (IAA), zeatin riboside (ZR) and gibberellin A3 (GA3) at 5 DAA, and maintained higher IAA and GA3 levels until 20 DAA. The ratios of ABA/IAA and ABA/GA3 were also reduced at both 5 and 20 DAA. These hormonal alterations optimized grain-filling dynamics, prolonged active filling duration and improved middle- and late-stage filling rates, thereby promoting grain weight accumulation and suppressing chalkiness formation. Compared with HT-K100, HT-K70+30 increased yield by 8.75%, which was attributed to improved seed-setting rate and 1000-grain weight. HT-K30+70 enhanced spikelet number per panicle, seed-setting rate and 1000-grain weight, but significantly decreased effective panicles, resulting in no obvious yield advantage. Furthermore, split K application effectively reduced grain chalkiness, with a more pronounced effect at a higher panicle-stage K proportion. Under ongoing global warming, K management can be tailored to production goals: higher basal K is preferable for yield pursuit, while increasing panicle K topdressing effectively improves grain quality. Full article
(This article belongs to the Topic New Trends in Crop Breeding and Sustainable Production)
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19 pages, 651 KB  
Article
Neurometabolic Signatures of Alexithymia and Visuospatial Abilities in Parkinson’s Disease: An Exploratory 1H-MRS Study of the Substantia Nigra and Globus Pallidus
by Laura Culicetto, Giulia Marafioti, Lilla Bonanno, Rosa Morabito, Gianluca Elio Fallica, Chiara Sorbera, Giuseppe Di Lorenzo, Silvia Marino, Angelo Quartarone and Rosella Ciurleo
J. Clin. Med. 2026, 15(11), 4236; https://doi.org/10.3390/jcm15114236 - 30 May 2026
Viewed by 269
Abstract
Background: Parkinson’s Disease (PD) is a multisystem neurodegenerative disorder associated with cognitive and emotional disturbances, including visuospatial deficits and alexithymia, which may substantially affect quality of life (QoL). The metabolic underpinnings of non-motor and emotional features within deep basal ganglia nuclei remain poorly [...] Read more.
Background: Parkinson’s Disease (PD) is a multisystem neurodegenerative disorder associated with cognitive and emotional disturbances, including visuospatial deficits and alexithymia, which may substantially affect quality of life (QoL). The metabolic underpinnings of non-motor and emotional features within deep basal ganglia nuclei remain poorly understood. This exploratory proof-of-concept study aimed to examine 1H-MRS-derived metabolite ratios in the substantia nigra (SN) and globus pallidus (GP) and to explore their preliminary associations with visuospatial-attentional abilities and alexithymia. Methods: Fifteen individuals with PD and 15 healthy controls (HCs) underwent Proton Magnetic Resonance Spectroscopy (1H-MRS) targeting the SN and GP bilaterally. Metabolite ratios were quantified with LCModel and analyzed as left, right, and hemisphere-averaged measures. PD participants completed a multidisciplinary assessment including motor severity, cognition, visuospatial abilities, mood and alexithymia. Multiple testing was controlled using false discovery rate (FDR). Given the between-group imbalance in age and education, exploratory covariate-adjusted sensitivity analyses were also performed. Results: PD participants were older, less educated, and showed lower global cognition than HCs, including significantly reduced MoCA scores (20.9 ± 6.6 vs. 28.7 ± 1.8; FDR-corrected p < 0.001). In uncorrected analyses, between-group metabolite comparisons showed lower myo-inositol (Ins) in the SN (p = 0.04) and higher glutamatergic signal in the right GP in PD relative to HCs (p = 0.03); however, these differences were not robust after adjustment for age, education and multiple testing. Within the PD group, an uncorrected right–left asymmetry was observed for pallidal Ins. Exploratory correlations suggested uncorrected associations between SN metabolites and alexithymia dimensions related to emotional awareness and verbalization, whereas GP metabolites were more frequently associated with selected visuospatial, attentional, language-related, and broader cognitive measures. None of these associations survived FDR correction. Conclusions: This exploratory proof-of-concept study provides preliminary feasibility data and effect-size estimates for future 1H-MRS investigations of basal ganglia metabolites in PD. Given the small sample size, lack of cognitive matching, age and education imbalance, and absence of correction-surviving associations, the findings should not be interpreted as evidence of PD-specific neurometabolic markers. Larger, prospectively matched, and adequately powered studies are needed. Full article
(This article belongs to the Section Clinical Neurology)
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27 pages, 925 KB  
Review
Amino Acids as Metabokines in Hypercatabolic States: Rethinking Nutritional Protein-Based Strategies Beyond Caloric Support
by Giovanni Corsetti and Evasio Pasini
Nutrients 2026, 18(11), 1703; https://doi.org/10.3390/nu18111703 - 27 May 2026
Viewed by 759
Abstract
The clinical management of nutrition in acute and chronic diseases requires an integrated understanding of the interactions between energy intake, dietary protein, and amino acids (AAs). Many conditions (including sepsis, major trauma, cancer cachexia, chronic heart failure, chronic obstructive pulmonary disease, renal and [...] Read more.
The clinical management of nutrition in acute and chronic diseases requires an integrated understanding of the interactions between energy intake, dietary protein, and amino acids (AAs). Many conditions (including sepsis, major trauma, cancer cachexia, chronic heart failure, chronic obstructive pulmonary disease, renal and liver failure, autoimmune diseases, and aging) share a common pathophysiological feature: the hypercatabolic state (HCS). HCS is characterized by systemic inflammation and neuroendocrine activation that increase basal metabolic rate, induce insulin resistance, and accelerate skeletal muscle proteolysis, leading to negative nitrogen balance, sarcopenia, and cachexia. Under these conditions, skeletal muscle acts as a metabolic reservoir of AAs mobilized to support energy production, gluconeogenesis, immune function, and vital organ metabolism, often at the expense of lean body mass and clinical outcomes. This narrative review examines the distinct and non-overlapping roles of calories, proteins, and AAs in metabolic regulation, with a particular focus on HCS. Calories primarily act as a permissive factor for protein utilization, whereas proteins and especially essential amino acids (EAAs) function not only as substrates for protein synthesis but also as signaling molecules (metabokines) regulating anabolic and catabolic pathways, including mTORC1 and AMPK. Energy provision alone is insufficient to prevent muscle loss when EAA availability is inadequate, while high protein intake without sufficient energy fails to sustain anabolism due to anabolic resistance. Evidence indicates that protein quality and the balanced availability of all EAAs are more critical for lean mass preservation than total caloric intake alone. Strategies based solely on calorie provision or protein quantity are therefore limited, whereas targeted EAA supplementation may partially overcome anabolic resistance in selected hypercatabolic conditions. Overall, this review supports a shift from calorie-centered nutrition toward a signal-based, quality-oriented approach, based on personalized needs, that integrates metabolic status, protein quality, and AA signaling to preserve lean body mass and improve clinical outcomes. Full article
(This article belongs to the Special Issue Dietary Amino Acid Metabolism in Human Health and Disease)
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28 pages, 1927 KB  
Article
Effects of Feeding Grapevine Branch–Leaf Silage on Growth Performance, Serum Biochemical Parameters, Rumen Microbial Diversity, and Metabolism in Kazakh Rams
by Kadeliya Abudureyimu, Linhai Song, Buweiaizhaer Maimaitimin, Subinuer Abuduli, Yuxin Zhou, Yongkuo Li, Zhijun Zhang, Wei Shao, Liang Yang and Wanping Ren
Animals 2026, 16(11), 1600; https://doi.org/10.3390/ani16111600 - 24 May 2026
Viewed by 827
Abstract
Grapevine branch and leaf silage (GBLS), a polyphenol-rich unconventional forage, exhibits antimicrobial and antioxidant properties that can benefit animal health and productivity. A total of 60 healthy six-month-old Kazakh rams (43.29 ± 4.55 kg, p > 0.05 for initial body weight among groups) [...] Read more.
Grapevine branch and leaf silage (GBLS), a polyphenol-rich unconventional forage, exhibits antimicrobial and antioxidant properties that can benefit animal health and productivity. A total of 60 healthy six-month-old Kazakh rams (43.29 ± 4.55 kg, p > 0.05 for initial body weight among groups) were randomly assigned to three dietary groups, each consisting of four replicates with five rams per replicate. The control group (CK) was fed a basal diet based on whole-plant corn silage, whereas the experimental groups received diets in which 50% (GBLS50%) or 100% (GBLS100%) of the corn silage was replaced with GBLS. A 10-day adaptation period preceded the 90-day formal feeding trial. Results showed a significant quadratic response for average daily gain (ADG) and average daily feed intake (ADFI) across GBLS substitution rates (p < 0.05), with the 50% level yielding the highest values. Specifically, ADFI at the 50% replacement level was significantly higher than that of the control (p < 0.05), confirming an inverted U-shaped response with 50% as the optimal substitution rate. However, in-depth analysis of serum biochemical parameters revealed that GBLS supplementation significantly reduced serum concentrations of total cholesterol, triglycerides, urea nitrogen, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA), while significantly increasing levels of immunoglobulins (IgA, IgM, IgG), superoxide dismutase (SOD), and catalase (CAT) (p < 0.05). Rumen fermentation analysis showed that the GBLS50% group had significantly lower concentrations of acetate, butyrate, and total volatile fatty acids (VFA) (p < 0.05). In the rumen microbiota study, no significant differences were observed in alpha or beta diversity or at the phylum level between groups (p > 0.05); however, the abundance of Lactobacillus gasseri was significantly reduced in the GBLS50% group (p < 0.05). Metabolomic profiling identified 43 significantly altered metabolites—27 upregulated (e.g., PE (18:1(9Z)/0:0) and 12,14-pentacosadiynoic acid) and 16 downregulated (e.g., deoxyadenosine). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis highlighted purine metabolism as a significantly altered pathway (p < 0.05), providing insight into the potential metabolic mechanisms underlying the physiological effects of GBLS in rams. In conclusion, replacing 50% of whole-plant corn silage with grapevine branch and leaf silage improves growth performance trends and significantly enhances immunity and antioxidant capacity in Kazakh rams. Full article
(This article belongs to the Section Small Ruminants)
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22 pages, 9718 KB  
Article
Effects of Dietary Glycerol Monolaurate on Growth Performance, Bile Acid Metabolism, and Intestinal Health in Asian Swamp Eel (Monopterus albus)
by Haiyan Liu, Hang Yang, Xiaogang Guo, Menghui Lin, Minjie Zhao, Wenzong Zhou and Haiying Cai
Animals 2026, 16(11), 1575; https://doi.org/10.3390/ani16111575 - 22 May 2026
Viewed by 347
Abstract
This study investigated the dose-dependent effects of dietary glycerol monolaurate (GML) supplementation on the growth performance, bile acid metabolism, and intestinal health of Asian swamp eel (Monopterus albus). A total of 225 healthy eels with an initial body weight of 25.0 [...] Read more.
This study investigated the dose-dependent effects of dietary glycerol monolaurate (GML) supplementation on the growth performance, bile acid metabolism, and intestinal health of Asian swamp eel (Monopterus albus). A total of 225 healthy eels with an initial body weight of 25.0 ± 2.0 g were randomly divided into three groups and fed a basal diet (control), 0.5 g/kg GML, or 1.0 g/kg GML for 60 days, respectively. The results showed that dietary GML supplementation increased the weight gain rate by 8.75% and decreased the feed conversion ratio by 8.16% in the GML1 group compared with the control. Dietary GML significantly reduced the contents of TP and ALB (p < 0.05). Meanwhile, the MDA content in the GML0.5 and GML1 groups decreased significantly by 24.80% and 38.15%, respectively. The contents of total bile acids and secondary bile acids were significantly elevated in the GML1 group (p < 0.05). In addition, GML supplementation optimized the intestinal microbial community and significantly reduced the relative abundance of potentially harmful bacteria such as Nocardia and Stenotrophomonas (p < 0.05). In conclusion, under the conditions of this study, dietary GML could effectively the improve growth performance, bile acid metabolism, antioxidant capacity, and intestinal health of M. albus. Among the tested concentrations, 1.0 g/kg GML showed the optimal beneficial effects. Full article
(This article belongs to the Section Aquatic Animals)
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17 pages, 2531 KB  
Article
The Relationship Between Meal Composition and the Body Composition of Wroclaw Medical University Students
by Aleksandra Jaremków, Iwona Markiewicz-Górka, Krzysztof Kraik, Krystyna Pawlas, Rafał Poręba, Małgorzata Poręba and Paweł Gać
Nutrients 2026, 18(10), 1602; https://doi.org/10.3390/nu18101602 - 18 May 2026
Viewed by 367
Abstract
Background/Objectives: Appropriate nutrition is a foundation for maintaining good health. Especially for young people, it determines the proper growth and development. The aim of the study was to investigate the relationship between the dietary makeup of young adults and their body composition parameters. [...] Read more.
Background/Objectives: Appropriate nutrition is a foundation for maintaining good health. Especially for young people, it determines the proper growth and development. The aim of the study was to investigate the relationship between the dietary makeup of young adults and their body composition parameters. Methods: A total of 297 students of Wroclaw Medical University participated in the study. A questionnaire was administered to assess meal composition, and body composition, phase angle, and basal metabolic rate (BMR) were evaluated. Results: The greatest differences were observed in the consumption of grains, animal protein, and dairy products. Meals consumed by males contained mostly animal protein and grain products, whereas females’ meals contained more fruit and vegetables. Correlations were observed between dinner, supper and the extracellular water/intracellular water (ECW/ICW) ratio, fat, water, and muscle body content, with r~ ±(0.134–0.163), and between the second breakfast and body mass index (BMI), and visceral fat level (respectively: −0.118; −0.149). Multivariate analysis indicated that consuming a balanced dinner has a significant impact on maintaining the appropriate proportions of body composition. Conclusions: Analysis of the results suggests that proper composition of meals is associated with a lower BMI, reduced fat content, increased muscle mass, and better body hydration. Full article
(This article belongs to the Special Issue Nutrient Intake and Food Patterns in Students)
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28 pages, 2113 KB  
Review
Bat-Inspired Longevity: Immune Damage Management and Nutritional Modulation for Healthy Aging
by Sunmin Park and James W. Daily
Int. J. Mol. Sci. 2026, 27(10), 4467; https://doi.org/10.3390/ijms27104467 - 16 May 2026
Viewed by 930
Abstract
The exceptional longevity of bats challenges classical theories of inflammaging and suggests an alternative that improved resilience in responding to pathogens and cellular damage can increase longevity. Accordingly, we have developed the Core Longevity State Vector (CLSV-6) to characterize an expanded explanation for [...] Read more.
The exceptional longevity of bats challenges classical theories of inflammaging and suggests an alternative that improved resilience in responding to pathogens and cellular damage can increase longevity. Accordingly, we have developed the Core Longevity State Vector (CLSV-6) to characterize an expanded explanation for inflammaging that can be predictive of successful aging and used to develop potential strategies for successful aging. Despite high metabolic rates and persistent viral exposure, many bat species have much longer lifespans than would be predicted for mammals of their size. The increased longevity of many bat species is achieved through damage tolerance, regulated inflammasome activity, constitutive basal antiviral defenses, enhanced autophagy–mitophagy, and efficient resolution of inflammation, rather than through heightened inflammatory immunity. The CLSV-6 is introduced as a multidimensional immunotype framework integrating six conserved mechanisms that link bat immunity to bat longevity and to human healthy aging: (1) damage tolerance, (2) autophagy–mitophagy, (3) proteostasis (management of degraded proteins), (4) basal immune readiness without activation, (5) inflammasome regulation, and (6) inflammatory resolution capacity. Together, these mechanisms enable a robust antiviral defense when needed without chronic inflammation. Notably, centenarians converge toward this bat-like configuration. Studies suggest that centenarians often preserve more functional NK cells, better macrophage regulation, and improved anti-inflammatory control, with both bats and humans exhibiting reduced activation of the NLRP3 inflammasome, resulting in greater immune resilience. Building on this framework, functional foods—including polyphenols, fermented foods, and herbal extracts—are proposed as practical strategies to shift human immunity toward bat-like, CLSV-6 immunotype by enhancing cellular quality control, regulating inflammasome activity, strengthening basal antiviral readiness, and supporting inflammatory resolution, thereby redirecting longevity strategies from immune stimulation toward damage containment and repair. This review reframes longevity as an emergent property of integrated immune damage management and provides a mechanistic roadmap for nutritional interventions to engineer healthier human aging inspired by bat immunity. Full article
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12 pages, 489 KB  
Article
Association Between Phase Angle, Muscle Mass Distribution, and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease
by Lyazat Ibrayeva, Irina Bacheva and Malika Sadibekova
J. Clin. Med. 2026, 15(10), 3839; https://doi.org/10.3390/jcm15103839 - 16 May 2026
Viewed by 376
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is associated with systemic alterations in body composition, including muscle mass loss and fat redistribution, which may influence patient-reported outcomes. However, the independent contribution of bioimpedance-derived parameters, particularly phase angle, to quality of life (QoL) remains [...] Read more.
Background: Chronic obstructive pulmonary disease (COPD) is associated with systemic alterations in body composition, including muscle mass loss and fat redistribution, which may influence patient-reported outcomes. However, the independent contribution of bioimpedance-derived parameters, particularly phase angle, to quality of life (QoL) remains unclear. Methods: This exploratory pilot study included 75 clinically stable patients with moderate-to-severe COPD (GOLD stages II–III). Body composition was assessed using segmental multi-frequency bioelectrical impedance analysis with the InBody 770 system. Evaluated parameters included fat-free mass (FFM), skeletal muscle mass (SMM), percent body fat (PBF), visceral fat area (VFA), extracellular water-to-total body water ratio (ECW/TBW), bone mineral content (BMC), and phase angle (PhA). Quality of life was assessed using the WHOQOL-BREF questionnaire. Associations between body composition parameters and QoL domains were analyzed using Spearman correlation analysis and multivariable linear regression models. Results: Despite a median body mass index (BMI) within the normal range (23.4 kg/m2), body fat mass exceeded reference values in both men and women. Fat-free mass and skeletal muscle mass were located near the lower range of expected values. Correlation analysis demonstrated predominantly weak associations between body composition parameters and QoL domains. Significant positive correlations were identified between the psychological QoL domain and fat-free mass (ρ = 0.238, p = 0.041), skeletal muscle mass (ρ = 0.240, p = 0.040), basal metabolic rate (ρ = 0.236, p = 0.043), and bone mineral content (ρ = 0.249, p = 0.033). In multivariable regression models, fat-free mass and skeletal muscle mass demonstrated consistent positive associations with both physical and psychological QoL domains. Whole-body and segmental phase angle parameters did not demonstrate significant associations with QoL outcomes. Conclusions: In patients with COPD, BMI alone may inadequately reflect underlying alterations in body composition. Muscle-related parameters, particularly fat-free mass and skeletal muscle mass, demonstrated more consistent associations with physical and psychological aspects of quality of life than obesity-related indicators. These findings suggest that bioelectrical impedance analysis may provide additional clinically relevant information beyond BMI when assessing body composition and quality of life in patients with COPD. Full article
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18 pages, 11196 KB  
Article
Effects of Epimedium Ultrafine Powder on Seminal Quality, Hormones, Immuno-Antioxidant Status, Gut Microbiota and Metabolites in Boars
by Jingbin He, Weiyi Li, Bin Ran, Yupeng Zhang, Junjie Wu, Yunxiang Zhao, Zhili Li and Mengjie Liu
Animals 2026, 16(10), 1520; https://doi.org/10.3390/ani16101520 - 15 May 2026
Viewed by 380
Abstract
Epimedium is a traditional Chinese tonic used to tonify the kidneys, enhance sexual function, and strengthen muscles and bones. However, the potential effects of Epimedium on the semen quality of Bama boars remain incompletely elucidated. The objective of this study was to evaluate [...] Read more.
Epimedium is a traditional Chinese tonic used to tonify the kidneys, enhance sexual function, and strengthen muscles and bones. However, the potential effects of Epimedium on the semen quality of Bama boars remain incompletely elucidated. The objective of this study was to evaluate the effects of dietary Epimedium ultrafine powder (EP) supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. The objective of this study was to evaluate the effects of dietary EP supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. Eighteen healthy, sexually mature adult male Bama boars were randomly divided into three groups (n = 6) and fed either a basal diet (CON) or the basal diet supplemented with 0.3% (EP3) or 0.5% (EP5) Epimedium ultrafine powder for five weeks. This study employed enzyme-linked immunosorbent assay (ELISA), 16S RNA gene sequencing, non-targeted metabolomics (CON and EP5), and Spearman correlation analysis, among other methods. The results indicated that dietary Epimedium (0.3% and 0.5%) increased the levels of serum TP, FSH, and SOD and decreased the abnormal sperm rate and the levels of serum TBA, TNF-α, and IL-6. Among them, adding 0.5% Epimedium in the diet increased sperm motility and the levels of serum T, LH, and IgG. 16S rRNA gene sequencing analysis revealed that both 0.3% and 0.5% Epimedium supplementation reduced the abundance of Streptococcus. Specifically, the 0.3% dose decreased Prevotella abundance, while the 0.5% dose reduced Escherichia-Shigella abundance. PICRUSt2 analysis revealed that the pathways of phenylalanine, butanoate, biotin, and arachidonic acid metabolism were significantly enriched in the Epimedium group. A non-targeted metabolomics analysis identified that indole-3-acrylic acid, DL-tryptophan, 2-hydroxyphenylalanine, and propionylcarnitine showed significant upregulation after Epimedium supplementation. Spearman correlation analysis indicated that Streptococcus was negatively correlated with sperm motility and serum-related parameters (TP, T, LH, IgM, and IgG). Streptococcus and Escherichia-Shigella were negatively correlated with indole-3-acrylic acid, DL-tryptophan, and biotin. In conclusion, Epimedium has a positive impact on the seminal quality, reproductive hormones, and immune–antioxidant levels of Bama boars by regulating the composition and metabolites of the intestinal microbiota. Full article
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12 pages, 1872 KB  
Article
A Boronic Acid-Based Glutamine Analog Forms a Covalent Adduct with Kidney-Type Glutaminase and Suppresses Triple-Negative Breast Cancer Cell Proliferation
by Thiruselvam Viswanathan, Dinesh Devadoss, Achyuta Nagaraj, Barry P. Rosen, Hitendra S. Chand and Venkadesh Sarkarai Nadar
Biomedicines 2026, 14(5), 1100; https://doi.org/10.3390/biomedicines14051100 - 13 May 2026
Viewed by 449
Abstract
Background: Cancer cells exhibit metabolic reprogramming characterized by increased dependence on glutamine to sustain rapid proliferation and biosynthetic demands. Kidney-type glutaminase (KGA), which catalyzes the first and rate-limiting step of glutamine metabolism, represents a promising therapeutic target, particularly in triple-negative breast cancer [...] Read more.
Background: Cancer cells exhibit metabolic reprogramming characterized by increased dependence on glutamine to sustain rapid proliferation and biosynthetic demands. Kidney-type glutaminase (KGA), which catalyzes the first and rate-limiting step of glutamine metabolism, represents a promising therapeutic target, particularly in triple-negative breast cancer (TNBC), an aggressive sub-type lacking effective targeted therapies. This study evaluated 2-amino-4-boronobutyric acid (ABBA), a boronic acid-containing glutamine analog, as a potential KGA inhibitor with anticancer activity. Methods: KGA inhibition was assessed using a fluorometric enzymatic assay. Cytotoxic effects were examined in multiple TNBC cell lines. Covalent docking and molecular simulation analysis were performed to characterize interactions between ABBA and the KGA active site. Results: ABBA potently inhibited KGA activity, with an IC50 of approximately 1.0 μM, demonstrating greater efficacy than several non-proteinogenic amino acid analogs. ABBA induced dose-dependent cytotoxicity across multiple TNBC cell lines, with pronounced sensitivity observed in basal sub-type cells and cellular sensitivity correlated with KGA expression levels. Expression of γ-glutamyl transpeptidase 1 (GGT1) was negligible, and, excluding any off-target effects, the observed anticancer effects are primarily attributed to KGA inhibition. Docking analysis indicated that ABBA forms a reversible covalent adduct with the catalytic Ser286 residue of KGA in a boronate tetrahedral geometry resembling transition-state mimics, while molecular simulation demonstrated stabilization of the complex through hydrogen bonding and electrostatic interactions. Conclusions: ABBA is a potent boron-based glutaminase inhibitor with therapeutic potential for targeting glutamine metabolism in TNBC. Further structural optimization and in vivo evaluation are warranted to advance ABBA toward therapeutic development. Full article
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21 pages, 4730 KB  
Article
Integrative Multi-Omics Reveal Silibinin Alleviates Heat Stress-Driven Hepatic Lipid Disruption in Laying Hens
by Jiang Gao, Hongrui Ren, Xuanfu Wu, Cunzhi Zou, Bin He and Wenqiang Ma
Int. J. Mol. Sci. 2026, 27(10), 4267; https://doi.org/10.3390/ijms27104267 - 11 May 2026
Viewed by 523
Abstract
Heat stress (HS) has emerged as a major environmental stressor, inducing oxidative stress and hepatic steatosis and impairing production performance and health in laying hens, with limited evidence-based nutritional interventions available. This study investigated the hepatoprotective effects of dietary silibinin (SIL) against chronic [...] Read more.
Heat stress (HS) has emerged as a major environmental stressor, inducing oxidative stress and hepatic steatosis and impairing production performance and health in laying hens, with limited evidence-based nutritional interventions available. This study investigated the hepatoprotective effects of dietary silibinin (SIL) against chronic HS. In a 10-week trial, 252 43-week-old Hy-Line Brown hens were exposed to daily HS (32 ± 1 °C, temperature–humidity index [THI] > 73) and fed either a basal diet or one supplemented with 100 mg/kg SIL. SIL significantly increased laying rate (p < 0.05) and improved albumen height, Haugh units, and shell strength by week 8 (p < 0.05). Histological analysis showed a 48% reduction in non-alcoholic fatty liver disease (NAFLD) activity score, with significantly decreased hepatic triglyceride content (p < 0.05); Oil Red O staining confirmed reduced lipid droplet accumulation. SIL restored redox balance by increasing plasma, hepatic total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) (p < 0.05), increasing hepatic catalase (CAT) and glutathione (GSH) levels while decreasing malondialdehyde (MDA) (p < 0.05). Untargeted plasma metabolomics identified 11 key metabolites related to 2-oxoglutarate and purine metabolism, while hepatic transcriptomics revealed 835 differentially expressed genes primarily in the PPAR signaling and fatty acid biosynthesis pathways. SIL suppressed de novo lipogenesis via downregulation of ACACA and FASN, and enhanced β-oxidation through upregulation of CPT1A and ACSL1 (p < 0.05). Molecular docking indicated favorable binding affinities between SIL and these targets, which was further supported by corresponding changes in protein expression via Western blotting. Correlation analysis revealed a consistent alignment between the upregulation of ACSL1/CPT1A and improvement in performance and antioxidant status, suggesting a coordinated metabolic shift. These findings emphasize the potential of SIL as a sustainable animal nutrition antioxidant additive, which can alleviate HS-induced lipid disorders in the liver of laying hens. Importantly, these hepatoprotective effects were demonstrated exclusively under chronic heat stress conditions; further studies incorporating a normothermic baseline are required to distinguish stress-specific mitigation from general metabolic stimulation. Full article
(This article belongs to the Special Issue The Latest Development of Molecular Research in Animal Nutrition)
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16 pages, 1155 KB  
Article
Angiopoietin-like Proteins 4 and 8 in Diabetic Complications: Associations with Neuropathy and Metabolic Parameters in Type 2 Diabetes
by Yuliyan Naydenov, Vera Karamfilova, Diana Nikolova, Savelia Yordanova, Zdravko Kamenov, Julieta Hristova and Antoaneta Trifonova Gateva
J. Clin. Med. 2026, 15(10), 3631; https://doi.org/10.3390/jcm15103631 - 9 May 2026
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Abstract
Background/Objectives: Angiopoietin-like proteins 4 and 8 (ANGPTL4 and ANGPTL8) are key regulators of lipid metabolism and inflammatory processes, with a potential role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its complications. This monocentric observational study evaluated serum levels of [...] Read more.
Background/Objectives: Angiopoietin-like proteins 4 and 8 (ANGPTL4 and ANGPTL8) are key regulators of lipid metabolism and inflammatory processes, with a potential role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its complications. This monocentric observational study evaluated serum levels of ANGPTL4 and ANGPTL8 in 160 participants (93 patients with T2DM and 67 controls without carbohydrate disturbances) and their associations with peripheral and cardiac autonomic neuropathy. Methods: This is a monocentric, cross-sectional, observational study conducted at the Endocrinology and Metabolic Disorders Clinic of Alexandrovska Hospital in Sofia, involving 160 participants and approved by the Ethics Committee of Medical University–Sofia, with all subjects providing written informed consent in accordance with the Declaration of Helsinki. The main methods included detailed clinical and anthropometric assessments, diagnosis of peripheral neuropathy via the Neuropathy Disability Score (NDS), evaluation of cardiac autonomic neuropathy using heart rate variability analysis and Ewing cardiovascular reflex tests, comprehensive laboratory investigations with fasting blood samples, measurement of serum ANGPTL4 and ANGPTL8 levels by ELISA kits, and statistical analysis performed with IBM SPSS version 25, using parametric and non-parametric tests, correlations, logistic regression, and ROC curves. Results: ANGPTL4 levels were significantly lower in patients with T2DM (12.6 ± 23.1 ng/mL vs. 21.5 ± 29.3 ng/mL; p = 0.033). In a multivariate model, higher values remained associated with lower odds of T2DM (OR per 1 SD = 0.634; p = 0.0424). ANGPTL8 demonstrated moderate discriminatory ability for cardiac autonomic neuropathy (AUC = 0.678; p = 0.007) in unadjusted analysis, but the association did not persist after covariate adjustment. ANGPTL4 showed inverse correlations with body weight, basal metabolic rate, and GGT. Conclusions: The results support the role of ANGPTL4 as a potential biomarker in metabolic disturbances and complications in T2DM, while ANGPTL8 remains mainly insignificant after correction for potential confounding factors. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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19 pages, 2019 KB  
Article
Associations of Dietary Antioxidant and Phytochemical Indices with Cognitive Function: Mediating Roles of Basal Metabolic Rate and Systemic Inflammation
by Yuebao Fu, Wenjing Wang, Junqiao You, Zijian Cheng, Yuhui Sun, Yijia Liu, Yongye Sun and Yuandi Xi
Antioxidants 2026, 15(5), 573; https://doi.org/10.3390/antiox15050573 - 1 May 2026
Viewed by 474
Abstract
Dietary antioxidants and phytochemicals are believed to support cognitive health, but evidence on composite dietary indices remains limited. This cross-sectional study of 1845 community-dwelling older adults in China investigated the associations of the composite dietary antioxidant index (CDAI) and dietary phytochemical index (DPI) [...] Read more.
Dietary antioxidants and phytochemicals are believed to support cognitive health, but evidence on composite dietary indices remains limited. This cross-sectional study of 1845 community-dwelling older adults in China investigated the associations of the composite dietary antioxidant index (CDAI) and dietary phytochemical index (DPI) with cognitive function and mild cognitive impairment (MCI). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA; Beijing version). MCI was diagnosed through a two-stage procedure: MoCA-based preliminary screening (with education-stratified cutoffs: 13/14 for illiterate, 19/20 for 1–6 years, 24/25 for ≥7 years) followed by neurologist confirmation. CDAI was calculated as the sum of the standardized intakes of six antioxidants (selenium, zinc, carotenoids, vitamin A, vitamin C, vitamin E); DPI was defined as the percentage of the total energy intake from phytochemical-rich foods (fruits, vegetables excluding potatoes, legumes including soy products, nuts, seeds, and whole grains). Multivariable linear regression, logistic regression, and receiver operating characteristic (ROC) curve analyses were performed. The basal metabolic rate (BMR) and systemic immune-inflammation index (SII; platelets × neutrophils/lymphocytes) were tested as potential statistical mediators. Each one-unit increase in CDAI was associated with a 0.068-point higher MoCA score (95% CI: 0.012–0.123), and each one-unit increase in DPI was associated with a 0.029-point higher MoCA score (95% CI: 0.008–0.050). BMR and SII partially mediated the association between CDAI and MoCA score, but temporal ordering remains unclear due to the cross-sectional design. When both CDAI and DPI were in the highest quartile, participants had a 46.3% lower risk of MCI compared with those with both indices in the lowest quartile (OR = 0.537, 95% CI: 0.308–0.935). A predictive model incorporating CDAI, inflammatory markers, and red blood cell parameters showed moderate discriminatory ability in this study sample (apparent AUC = 0.731, bootstrap-corrected AUC = 0.728). These findings suggest that a higher combined dietary antioxidant and phytochemical intake may be jointly associated with better cognitive function, although the cross-sectional design precludes causal inference. Full article
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