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Search Results (161)

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18 pages, 2549 KB  
Article
Biochar and Arbuscular Mycorrhizal Fungi Promote Rice Paddy Phosphorus Cycle by Altering Soil Phosphorus Turnover and Leaf Phosphorus Distribution
by Zhonghua Wen, Xu Yang, Xuanwei Zhou, Yongjia Shi, Haoyue Zheng and Jun Meng
Agronomy 2025, 15(11), 2562; https://doi.org/10.3390/agronomy15112562 - 6 Nov 2025
Viewed by 339
Abstract
Biochar and arbuscular mycorrhizal fungi (AMF) make significant contributions to improving soil and plant mineral nutrition, primarily phosphorus (P). However, the response of soil and leaf P fractions dynamics to biochar and AMF amendment in paddy ecosystems remains unclear. A pot experiment in [...] Read more.
Biochar and arbuscular mycorrhizal fungi (AMF) make significant contributions to improving soil and plant mineral nutrition, primarily phosphorus (P). However, the response of soil and leaf P fractions dynamics to biochar and AMF amendment in paddy ecosystems remains unclear. A pot experiment in greenhouse was conducted to study the effects of three biochars produced from rice husk (HBC), maize straw (MBC), and wood chips (WBC) and Rhizophagus irregularis on soil and leaf P fractions, soil chemical properties, and rice growth. The combination of biochar and AMF increased soil content of labile inorganic P (38.25%, 50.87% and 23.65%, respectively) and decreased that of labile organic P (52.31%, 61.12% and 44.60%, respectively) compared to the control. Similarly, HBC and MBC with AMF combination increased leaf contents of inorganic (7.29% and 8.81%, respectively) and nucleic acid (18.75% and 14.73%, respectively) P, which were strongly correlated with soil labile P fractions. Biochar and AMF amendment governed the transformation of soil P by altering total P, organic matter, and pH. Meanwhile, the distribution of leaf P was influenced by leaf total P content, soil organic matter, and electrical conductivity (EC). In addition, MBC and HBC increased the rice mycorrhizal colonization rate by 6.78% and 18.19%, respectively. The application of HBC and AMF increased leaves’ and stems’ biomass (28.57% and 26.67%, respectively), and three biochars and AMF also facilitated P accumulation in rice. Therefore, these results provide the first evidence for the interaction between biochar and AMF to alter P distribution among leaf fractions in paddy fields. Full article
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21 pages, 2678 KB  
Article
Potassium-Hydroxide-Based Extraction of Nicotinamide Adenine Dinucleotides from Biological Samples Offers Accurate Assessment of Intracellular Redox Status
by Tamas Faludi, Daniel Krakko, Jessica Nolan, Robert Hanczko, Akshay Patel, Zach Oaks, Evan Ruggiero, Joshua Lewis, Xiaojing Wang, Ting-Ting Huang, Ibolya Molnar-Perl and Andras Perl
Int. J. Mol. Sci. 2025, 26(21), 10371; https://doi.org/10.3390/ijms262110371 - 24 Oct 2025
Viewed by 409
Abstract
The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide [...] Read more.
The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide which act as signaling molecules. Monitoring NADPH levels, NADPH/NADP+ ratio, and especially distinguishing from NADH, provides vital information about cellular redox status, energy generation, survival, lineage specification, and death pathway selection. NADPH detection is key to understanding metabolic reprogramming in cancer, aging, and cardiovascular, hormonal, neurodegenerative, and autoimmune diseases. Liquid chromatography combined with mass spectrometry (LC-MS) is crucial for NADPH detection in redox signaling because it offers the high sensitivity, specificity, and comprehensive profiling needed to quantify this vital but labile redox cofactor in complex biological samples. Using hepatoma cell lines, liver tissues, and primary hepatocytes from mice lacking transaldolase or nicotinamide nucleotide transhydrogenase, or having lupus, this study demonstrates that accurate measurement of NADPH depends on its preservation in reduced form which can be optimally achieved by extraction of metabolites in alkaline solution, such as 0.1 M potassium hydroxide (KOH) in comparison to 80% methanol (MeOH) alone or 40:40:20 methanol/acetonitrile/formic acid solution. While KOH extraction coupled with hydrophilic interaction liquid chromatography (HILIC) and mass spectrometry most reliably detects NADPH, NADP, NADH, NAD, polyamines, and polyols, MeOH extraction is best suited for detection of glutathione and overall discrimination between complex metabolite extracts. This study therefore supports performing parallel KOH and MeOH extractions to enable comprehensive metabolomic analysis of redox signaling. Full article
(This article belongs to the Special Issue ROS Signalling and Cell Turnover)
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13 pages, 1722 KB  
Article
Interactions Between Soil Texture and Cover Crop Diversity Shape Carbon Dynamics and Aggregate Stability
by Vladimír Šimanský and Martin Lukac
Land 2025, 14(10), 2044; https://doi.org/10.3390/land14102044 - 13 Oct 2025
Viewed by 448
Abstract
Increasing attention is being paid to the use of cover crops as a means of improving soil quality, particularly in relation to soil organic matter (SOM) accumulation and aggregate stability. This study evaluated the effects of soil texture, soil depth, and cover crop [...] Read more.
Increasing attention is being paid to the use of cover crops as a means of improving soil quality, particularly in relation to soil organic matter (SOM) accumulation and aggregate stability. This study evaluated the effects of soil texture, soil depth, and cover crop type on soil organic carbon (Corg), labile carbon (CL), and soil structure under field conditions in western Slovakia. A field experiment compared two texturally distinct Phaeozem soils—silty clay loam and sandy loam —and two cover cropping strategies: pea (Pisum sativum L.) monoculture and a four-species mixture of flax (Linum usitatissimum L.), camelina (Camelina sativa L.), white mustard (Sinapis alba L.), and Italian millet (Setaria italica L.). Fine-textured soil accumulated up to 50% more Corg and 1.5 times more CL than sandy soil, while aggregate stability was up to 90% higher. The surface layer (0–10 cm) contained more SOM, but the deeper layer (10–20 cm) showed greater aggregate stability. Pea cultivation increased total organic carbon, whereas the diverse mixture enhanced labile carbon content and promoted the formation of smaller yet more stable aggregates. Strong correlations between CL and aggregate stability confirmed the key role of labile organic matter fractions in soil structural stabilisation. Overall, the results demonstrate that the interaction between soil texture and cover crop diversity critically shapes SOM dynamics and soil structure. Combining diverse cover crops with fine-textured soils provides an effective strategy to enhance soil quality, carbon sequestration, and long-term agricultural sustainability. Full article
(This article belongs to the Section Land, Soil and Water)
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16 pages, 2528 KB  
Article
The Biosorption of Cadmium, Lead, and Arsenic Using Garlic Byproducts and Their Potential for Metal Immobilization in Soil
by Jin Hee Park
Sustainability 2025, 17(19), 8857; https://doi.org/10.3390/su17198857 - 3 Oct 2025
Viewed by 754
Abstract
Metal contamination poses serious environmental and human health risks, which results in the need for low-cost remediation approaches. The utilization of agricultural byproducts for the removal of metal contaminants is considered cost-effective and environmentally sustainable. Garlic byproducts are rich in sulfur-containing compounds, and [...] Read more.
Metal contamination poses serious environmental and human health risks, which results in the need for low-cost remediation approaches. The utilization of agricultural byproducts for the removal of metal contaminants is considered cost-effective and environmentally sustainable. Garlic byproducts are rich in sulfur-containing compounds, and various functional groups contribute to metal binding. This study aimed to evaluate the potential of garlic stem and peel for the removal of cadmium (Cd), lead (Pb), and arsenic (As) from aqueous solutions and for their immobilization in contaminated soils. Batch sorption experiments conducted at pH 7 for 24 h showed that garlic stem removed 71.5% of Cd and 70.8% of Pb, while garlic peel achieved 65.4% and 79.4% removal, respectively. The higher Pb removal by garlic peel might be attributed to its higher sulfur content. However, both byproducts were less effective in removing As(III) and showed negligible removal of As(V), as these species predominantly occur in neutral or negatively charged species at neutral pH, resulting in weak interactions with negatively charged surface functional groups. Soil incubation experiments were conducted using 1% and 5% amendments of garlic stem and peel in Pb- and As-contaminated soils. Extractable Pb concentrations significantly increased in soils treated with 1% garlic peel because of the formation of labile complexes of Pb with dissolved organic carbon. However, a column experiment to evaluate the impact on Pb mobility under saturated and unsaturated conditions showed that Pb concentration in soil pore water decreased with garlic stem. Pb concentration was lower under saturated conditions, possibly due to the precipitation of Pb as PbS. Although the short-term application of raw agricultural byproducts increased extractable metal concentrations, long-term incubation reduced Pb levels in pore water. These findings suggest that unmodified garlic stem is a promising, cost-effective amendment for Pb immobilization in soil. Nevertheless, caution is needed in its application to prevent unintended metal mobilization in soil. Full article
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20 pages, 2100 KB  
Article
Fe2+-Sensing α-Synuclein Iron-Responsive Messenger RNA/eIF4F Complex Binding and Regulating mRNA Translation Activation and Repression
by Mateen A. Khan
Int. J. Mol. Sci. 2025, 26(19), 9320; https://doi.org/10.3390/ijms26199320 - 24 Sep 2025
Viewed by 393
Abstract
Alpha-synuclein (α-Syn) protein plays a crucial role in the pathophysiology of Parkinson’s disease (PD). In the 5′-untranslated regions (5′-UTRs) of α-Syn, mRNA has a structured iron-responsive element (IRE) with a stem loop that regulates translation. Iron (labile as Fe2+) enhances protein [...] Read more.
Alpha-synuclein (α-Syn) protein plays a crucial role in the pathophysiology of Parkinson’s disease (PD). In the 5′-untranslated regions (5′-UTRs) of α-Syn, mRNA has a structured iron-responsive element (IRE) with a stem loop that regulates translation. Iron (labile as Fe2+) enhances protein synthesis rates through an IRE mRNA. This investigation aimed to describe the way in which α-Syn IRE interacts with eIF4F and establish a relationship between binding affinity and translation efficiency. The strong binding affinity of α-Syn IRE with eIF4F was demonstrated by a fluorescence-based experiment, with Ka = 8.4 × 106 M−1 at 25 °C. Fe2+ further increased (~three-fold) the affinity of α-Syn IRE with eIF4F, outcompeting binding with IRP1. With an increase in temperature (10–30 °C), Kd values increased from 35.8 ± 1.6 nM to 158 ± 8.7 nM for the interaction of α-Syn IRE with eIF4F; however, adding Fe2+ demonstrated significantly increased affinity throughout the same temperature range. Thermodynamic analyses demonstrated that α-Syn IRE/eIF4F binding occurred spontaneously, with the presence of van der Waals and hydrogen bonding. Fe2+ enhanced the α-Syn IRE/eIF4F complex’s change in enthalpic and binding free energy contributions, which led to a more stable complex formation through the involvement of more hydrogen bonding. Exogenous addition of eIF4F in depleted WG or RR lysates restored α-Syn protein synthesis. Fe2+ further boosted α-Syn mRNA translation. IRP1 repressed α-Syn translation, although the addition of Fe2+ reversed this effect by boosting activator eIF4F binding and decreasing repressor IRP1 binding. These findings reveal the significance of iron in the α-synuclein mRNA regulatory process and validate its contribution as a strong enhancer of α-Syn mRNA translation. Full article
(This article belongs to the Section Macromolecules)
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14 pages, 1622 KB  
Article
Vertical Differentiation Characteristics and Environmental Regulatory Mechanisms of Microbial Biomass Carbon and Nitrogen in Coastal Wetland Sediments from the Northern Yellow Sea
by Yue Zhang, Haiting Xu and Jian Zhou
Sustainability 2025, 17(17), 8082; https://doi.org/10.3390/su17178082 - 8 Sep 2025
Viewed by 652
Abstract
Coastal saltmarsh wetlands play a pivotal role in global carbon and nitrogen cycling, yet the vertical distribution characteristics of sediment carbon and nitrogen and their regulatory mechanisms remain uncertain. Microbial biomass carbon (MBC) and nitrogen (MBN) serve as critical [...] Read more.
Coastal saltmarsh wetlands play a pivotal role in global carbon and nitrogen cycling, yet the vertical distribution characteristics of sediment carbon and nitrogen and their regulatory mechanisms remain uncertain. Microbial biomass carbon (MBC) and nitrogen (MBN) serve as critical indicators of ecosystem functioning, representing the most labile organic fractions that directly mediate biogeochemical processes in coastal wetlands. We investigated Yalu River Estuary coastal wetlands in the northern Yellow Sea. Sediment cores (0–100 cm depth) were collected and stratified into 20-cm intervals to analyse physicochemical properties and carbon–nitrogen indicators, enabling quantitative assessment of vertical distribution patterns and environmental drivers. The key findings are as follows: (1) Both microbial biomass carbon (MBC) and nitrogen (MBN) exhibited significant depth-dependent decreases, with MBC decreasing sharply by 45% (90.42 to 60.06 mg/kg) in the 40–60 cm layer and MBN decreasing by 50% (7.50 to 3.72 mg/kg) in the 80–100 cm layer. Total carbon (TC) peaked in the 40–60 cm layer (6.49 g/kg), whereas total nitrogen (TN) continuously decreased (from 0.51 (surface) to 0.24 g/kg (bottom)). (2) Depth-specific controls were identified: Surface layers (0–20 cm) were governed by tidal scouring (causing TC loss) and pH buffering; subsurface layers (20–40 cm) were constrained by moisture content (MC) and bulk density (BD), with partial mitigation by labile TC; and deeper layers (40–100 cm) were dominated by chemical factors exhibiting TN limitation and high electrical conductivity (EC). Understanding these microbial biomass dynamics is particularly crucial for predicting how coastal wetlands will respond to climate change and anthropogenic disturbances, as MBC and MBN serve as sensitive early-warning indicators of ecosystem health. Notably, MBC and MBN in northern Yellow Sea coastal wetlands are regulated primarily by physical—biological interactions in surface sediments and chemical stressors in deeper layers, providing crucial theoretical foundations for precise wetland carbon sink assessment and sustainable ecosystem management. Full article
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30 pages, 1177 KB  
Review
Iron–Inflammasome Crosstalk in Adipose Tissue: Unresolved Roles of NLRP3 and IL-1β in Metabolic Inflammation
by Sixtus Aguree
Int. J. Mol. Sci. 2025, 26(17), 8304; https://doi.org/10.3390/ijms26178304 - 27 Aug 2025
Cited by 1 | Viewed by 1552
Abstract
Iron is essential for cellular respiration, oxidative defense, and host immunity, but its dysregulation is increasingly associated with metabolic disorders, such as obesity and type 2 diabetes. In these diseases, regional iron accumulation occurs in adipose tissue, independent of systemic overload. This process [...] Read more.
Iron is essential for cellular respiration, oxidative defense, and host immunity, but its dysregulation is increasingly associated with metabolic disorders, such as obesity and type 2 diabetes. In these diseases, regional iron accumulation occurs in adipose tissue, independent of systemic overload. This process disrupts the mitochondrial redox balance, induces ferroptotic stress, and activates the innate immune pathways. Recent studies have highlighted the NLRP3 (nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing protein 3) inflammasome and its effector cytokine interleukin-1β (IL-1β) as important mediators of the interface between iron and inflammation. In both adipocytes and macrophages, labile iron increased reactive oxygen species (ROS) production and promoted inflammasome formation. Simultaneously, metabolic stress factors upregulate hepcidin expression, suppress ferroportin activity and exacerbate intracellular iron retention. These molecular events converge to maintain low-grade inflammation and impair insulin signaling. Despite these compelling associations, direct mechanistic evidence remains limited, particularly with respect to depot-specific responses and cell type resolution. In this review, I examine the current evidence linking iron handling and inflammasome biology in adipose tissue, focusing on ferroptosis, thioredoxin-interacting protein (TXNIP) signaling, and spatial mapping of iron–cytokine networks. I also discuss novel therapeutic strategies targeting iron overload and inflammasome activation, including chelation, hepcidin modulation, and inflammasome inhibition in the context of metabolic diseases. Full article
(This article belongs to the Special Issue Future Perspectives and Challenges: Interleukins in Immune Diseases)
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15 pages, 3465 KB  
Article
Identification of Bioactive Peptides from Caenorhabditis elegans Secretions That Promote Indole-3-Acetic Acid Production in Arthrobacter pascens ZZ21
by Shan Sun, Mengsha Li, Luchen Tao, Xiran Liu, Lei Ouyang, Gen Li, Feng Hu and Huixin Li
Microorganisms 2025, 13(8), 1951; https://doi.org/10.3390/microorganisms13081951 - 21 Aug 2025
Viewed by 634
Abstract
Caenorhabditis elegans, a free-living nematode model, secretes neuropeptides, but the ecological roles of its peptide exudates in regulating rhizosphere microbial activity remain largely unexplored. We identified six short peptides (P1, P9, P19, P20, P25, and P26) from C. elegans exudates that significantly [...] Read more.
Caenorhabditis elegans, a free-living nematode model, secretes neuropeptides, but the ecological roles of its peptide exudates in regulating rhizosphere microbial activity remain largely unexplored. We identified six short peptides (P1, P9, P19, P20, P25, and P26) from C. elegans exudates that significantly enhanced indole-3-acetic acid (IAA) production by the plant growth-promoting bacterium Arthrobacter pascens ZZ21. These peptides were heat-labile and proteinase K-sensitive but unaffected by DNase I or RNase A, confirming their proteinaceous (peptide) nature rather than nucleic acid origin. The retention of bioactivity in n-butanol extracts further supported their hydrophilic, peptide-like properties. LC-MS/MS identified 30 linear peptides, including the six bioactive ones, which exhibited distinct dose-dependent effects, suggesting diverse regulatory mechanisms. Despite their relatively low abundance, these peptides strongly promoted IAA production in the bacterial culture system across multiple concentrations. These findings reveal an unrecognized mechanism whereby free-living nematodes regulate rhizobacterial metabolism via secreted peptides, offering new insights into nematode-mediated chemical signaling. Therefore, this study advances understanding of plant–microbe–nematode interactions and highlights strategies for manipulating rhizosphere microbiota in sustainable agriculture. Full article
(This article belongs to the Section Plant Microbe Interactions)
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29 pages, 2598 KB  
Review
Exploring the Integration of Anthocyanins with Functional Materials in Smart Food Packaging: From Stabilization to Application
by Xiaowei Huang, Ke Zhang, Zhihua Li, Junjun Zhang, Xiaodong Zhai, Ning Zhang, Liuzi Du and Zhou Qin
Foods 2025, 14(16), 2896; https://doi.org/10.3390/foods14162896 - 20 Aug 2025
Cited by 2 | Viewed by 2497
Abstract
Anthocyanins, the most ubiquitous water-soluble phytopigments in terrestrial flora, have garnered substantial attention in sustainable food packaging research owing to their exceptional chromatic properties, pH-responsive characteristics, and putative health-promoting effects. Nevertheless, their inherent chemical lability manifests as rapid chromatic fading, structural degradation, and [...] Read more.
Anthocyanins, the most ubiquitous water-soluble phytopigments in terrestrial flora, have garnered substantial attention in sustainable food packaging research owing to their exceptional chromatic properties, pH-responsive characteristics, and putative health-promoting effects. Nevertheless, their inherent chemical lability manifests as rapid chromatic fading, structural degradation, and compromised bioactivity/bioavailability, ultimately restricting industrial implementation and incurring significant economic penalties. Recent advances in stabilization technologies through molecular encapsulation within polymeric matrices or nanoscale encapsulation systems have demonstrated remarkable potential for preserving anthocyanin integrity while augmenting multifunctionality. The integration of anthocyanins into advanced functional materials has emerged as a promising strategy for enhancing food safety and extending shelf life through smart packaging solutions. Despite their exceptional chromatic and bioactive properties, anthocyanins face challenges such as chemical instability under environmental stressors, limiting their industrial application. Recent advancements in stabilization technologies, including molecular encapsulation within polymeric matrices and nanoscale systems, have demonstrated significant potential in preserving anthocyanin integrity while enhancing multifunctionality. This review systematically explores the integration of anthocyanins with natural polymers, nanomaterials, and hybrid architectures, focusing on their roles as smart optical sensors, bioactive regulators, and functional components in active and smart packaging systems. Furthermore, the molecular interactions and interfacial phenomena governing anthocyanin stabilization are elucidated. The review also addresses current technological constraints and proposes future directions for scalable, sustainable, and optimized implementations in food preservation. Full article
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18 pages, 930 KB  
Article
Adding L-Carnitine and Selenium to Methimazole in Graves’ Disease: A Prospective Randomized Trial on Thyroid Markers and Quality of Life
by Mattia Rossi, Letizia Meomartino, Marco Zavattaro, Gloria Selvatico, Ruth Rossetto Giaccherino and Loredana Pagano
Nutrients 2025, 17(16), 2693; https://doi.org/10.3390/nu17162693 - 20 Aug 2025
Viewed by 3996
Abstract
Background: The therapeutic response in Graves’ Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties [...] Read more.
Background: The therapeutic response in Graves’ Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties of L-carnitine (LCT) on thyroid hormone action and the immunomodulatory role of selenium (Se), we aimed to assess the impact of adding a combined LCT and Se supplement to standard methimazole (MMI) therapy on the biochemical profile and quality of life (QoL) of patients with overt GD. Methods: This multicenter prospective randomized trial enrolled 60 consecutive patients with newly diagnosed overt GD. Participants were randomized to receive either standard treatment with MMI alone (Control Group) or MMI plus the combined LCT/Se supplement (Intervention Group). TSH, fT3, fT4, and TSH–receptor antibodies (TRAb) levels were evaluated every two months for up to 24 months or until spontaneous remission or definitive therapy. At each visit, patients completed a symptom questionnaire addressing the frequency of typical thyrotoxic symptoms. Results: No significant differences were observed between groups in the trend or time-to-normalization of TSH, fT3, and fT4 levels. However, the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14–4.81), p = 0.016), with a synergistic interaction with MMI therapy. MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020). The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35–46.11), p < 0.001). Overall symptom burden did not differ significantly between groups; however, the supplement exerted an independent effect in reducing the severity of tremor, irritability, mood lability, heat intolerance, and exertional dyspnea. Conclusions: Our findings suggest the clinical benefits of adding combined LCT and Se supplementation to MMI in the treatment of overt GD, including shorter disease duration, lower cumulative MMI exposure and earlier TRAb normality, that could positively influence TRAb-related prognostic outcomes. Full article
(This article belongs to the Section Nutrition and Metabolism)
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17 pages, 1315 KB  
Review
The Shuttling of Methyl Groups Between Folate and Choline Pathways
by Jonathan Bortz and Rima Obeid
Nutrients 2025, 17(15), 2495; https://doi.org/10.3390/nu17152495 - 30 Jul 2025
Cited by 2 | Viewed by 3511
Abstract
Methyl groups can be obtained either from the diet (labile methyl groups) or produced endogenously (methylneogenesis) via one-carbon (C1-) metabolism as S-adenosylmethionine (SAM). The essential nutrients folate and choline (through betaine) are metabolically entwined to feed their methyl groups into C1-metabolism. A choline-deficient [...] Read more.
Methyl groups can be obtained either from the diet (labile methyl groups) or produced endogenously (methylneogenesis) via one-carbon (C1-) metabolism as S-adenosylmethionine (SAM). The essential nutrients folate and choline (through betaine) are metabolically entwined to feed their methyl groups into C1-metabolism. A choline-deficient diet in rats produces a 31–40% reduction in liver folate content, 50% lower hepatic SAM levels, and a doubling of plasma homocysteine. Similarly, folate deficiency results in decreased total hepatic choline. Thus, sufficient intakes of both folate and choline (or betaine) contribute to safeguarding the methyl balance in the body. A significant amount of choline (as phosphatidylcholine) is produced in the liver via the SAM-dependent phosphatidylethanolamine methyltransferase. Experimental studies using diets deficient in several methyl donors have shown that supplemental betaine was able to rescue not only plasma betaine but also plasma folate. Fasting plasma homocysteine concentrations are mainly determined by folate intake or status, while the effect of choline or betaine on fasting plasma homocysteine is minor. This appears to contradict the finding that approximately 50% of cellular SAM is provided via the betaine-homocysteine methyltransferase (BHMT) pathway, which uses dietary choline (after oxidation to betaine) or betaine to convert homocysteine to methionine and then to SAM. However, it has been shown that the relative contribution of choline and betaine to cellular methylation is better reflected by measuring plasma homocysteine after a methionine load test. Choline or betaine supplementation significantly lowers post-methionine load homocysteine, whereas folate supplementation has a minor effect on post-methionine load homocysteine concentrations. This review highlights the interactions between folate and choline and the essentiality of choline as a key player in C1-metabolism. We further address some areas of interest for future work. Full article
(This article belongs to the Section Nutrigenetics and Nutrigenomics)
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26 pages, 808 KB  
Review
A Review of Formulation Strategies for Cyclodextrin-Enhanced Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs)
by Tarek Alloush and Burcu Demiralp
Int. J. Mol. Sci. 2025, 26(13), 6509; https://doi.org/10.3390/ijms26136509 - 6 Jul 2025
Cited by 2 | Viewed by 2572
Abstract
The advancement of efficient drug delivery systems continues to pose a significant problem in pharmaceutical sciences, especially for compounds with limited water solubility. Lipid-based systems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have emerged as viable options owing to their [...] Read more.
The advancement of efficient drug delivery systems continues to pose a significant problem in pharmaceutical sciences, especially for compounds with limited water solubility. Lipid-based systems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have emerged as viable options owing to their biocompatibility, capability to safeguard labile chemicals, and potential for prolonged release. Nonetheless, the encapsulation efficiency (EE) and release dynamics of these carriers can be enhanced by including cyclodextrins (CDs)—cyclic oligosaccharides recognized for their ability to form inclusion complexes with hydrophobic compounds. This article offers an extensive analysis of CD-modified SLNs and NLCs as multifunctional drug delivery systems. The article analyses the fundamental principles of these systems, highlighting the pre-complexation of the drug with cyclodextrins before lipid incorporation, co-encapsulation techniques, and surface adsorption after formulation. Attention is concentrated on the physicochemical interactions between cyclodextrins and lipid matrices, which influence essential factors such as particle size, encapsulation efficiency, and colloidal stability. The review includes characterization techniques, such as particle size analysis, zeta potential measurement, drug release studies, and Fourier-transform infrared spectroscopy (FT-IR)/Nuclear Magnetic Resonance (NMR) analyses. The study highlights the application of these systems across many routes of administration, including oral, topical, and mucosal, illustrating their adaptability and potential for targeted delivery. The review outlines current formulation challenges, including stability issues, drug leakage, and scalability concerns, and proposes solutions through advanced approaches, such as stimuli-responsive release mechanisms and computer modeling for system optimization. The study emphasizes the importance of regulatory aspects and outlines future directions in the development of CD-lipid hybrid nanocarriers, showcasing its potential to revolutionize the delivery of poorly soluble drugs. Full article
(This article belongs to the Special Issue Research on Cyclodextrin)
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17 pages, 1888 KB  
Article
The Orthovanadate-Catalyzed Formation of a Thermally Inert and Low-Redox-Potential Melanin
by Eric VanArsdale, Olufolasade Atoyebi, Okhil Nag, Matthew Laskoski, Evan Glaser, Eunkeu Oh, Gary J. Vora and Zheng Wang
Int. J. Mol. Sci. 2025, 26(12), 5537; https://doi.org/10.3390/ijms26125537 - 10 Jun 2025
Cited by 1 | Viewed by 717
Abstract
Catechol-like compounds are found throughout biology in the form of both redox-active and metal-binding functional groups. Within the marine environment, catechol groups are known to coordinate strongly with vanadate and ferric ions, and this binding is regulated through redox mechanisms. While investigating marine [...] Read more.
Catechol-like compounds are found throughout biology in the form of both redox-active and metal-binding functional groups. Within the marine environment, catechol groups are known to coordinate strongly with vanadate and ferric ions, and this binding is regulated through redox mechanisms. While investigating marine melanin formation in vitro, we found that DOPA, a catechol-containing amino acid, reacts with both metals differently when provided with sulfite, a weak reductant, and selenite, a weak oxidant. Both compounds interacted with the DOPA–vanadium complex, but only selenite, the more redox-labile chalcogenide, led to the creation of melanin particulates. When DOPA, vanadate, and selenite are present together, a metal-binding spectra shift and a melanin variant are rapidly observed. This variant was found to form large, elongated filaments with a low carboxylic acid content and a unique electron paramagnetic resonance signature. When compared to enzymatically produced melanin, this chemically synthesized variant was more thermally and biologically inert, exhibiting a lower redox activity. The results demonstrate that the regulation of the redox environment from metal–catechol interactions can help to control both the chemical and physical properties of melanin aggregates, suggesting a scalable and cell- and enzyme-free synthesis pathway for applications that may require inert materials of strict composition. Full article
(This article belongs to the Special Issue Melanin and Other Pigments: Function, Synthesis and Characterization)
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17 pages, 1722 KB  
Article
Effect of Alpha-1 Antitrypsin Deficiency on Zinc Homeostasis Gene Regulation and Interaction with Endoplasmic Reticulum Stress Response-Associated Genes
by Juan P. Liuzzi, Samantha Gonzales, Manuel A. Barbieri, Rebecca Vidal and Changwon Yoo
Nutrients 2025, 17(11), 1913; https://doi.org/10.3390/nu17111913 - 2 Jun 2025
Viewed by 1249
Abstract
Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in the SERPINA1 gene, leading to reduced levels or impaired alpha-1 antitrypsin (AAT) function. This condition predominantly affects the lungs and liver. The Z allele, a specific mutation in the SERPINA1 [...] Read more.
Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in the SERPINA1 gene, leading to reduced levels or impaired alpha-1 antitrypsin (AAT) function. This condition predominantly affects the lungs and liver. The Z allele, a specific mutation in the SERPINA1 gene, is the most severe form and results in the production of misfolded AAT proteins. The misfolded proteins accumulate in the endoplasmic reticulum (ER) of liver cells, triggering ER stress and activating the unfolded protein response (UPR), a cellular mechanism designed to restore ER homeostasis. Currently, there is limited knowledge regarding specific nutritional recommendations for patients with AATD. The liver is essential for the regulation of zinc homeostasis, with zinc widely recognized for its hepatoprotective properties. However, the effects of AATD on zinc metabolism remain poorly understood. Similarly, the potential benefits of zinc supplementation for individuals with AATD have not been thoroughly investigated. Objective: This study explored the relationship between AATD and zinc metabolism through a combination of in vitro experiments and computational analysis. Results: The expression of the mutant Z variant of ATT (ATZ) in cultured mouse hepatocytes was associated with decreased labile zinc levels in cells and dysregulation of zinc homeostasis genes. Analysis of two data series from the Gene Expression Omnibus (GEO) revealed that mice expressing ATZ (PiZ mice), a murine model of AATD, exhibited significant differences in mRNA levels related to zinc homeostasis and UPR when compared to wildtype mice. Bayesian network analysis of GEO data uncovered novel gene-to-gene interactions among zinc transporters, as well as between zinc homeostasis, UPR, and other associated genes. Conclusions: The findings provide valuable insights into the role of zinc homeostasis genes in UPR processes linked to AATD. Full article
(This article belongs to the Section Nutrigenetics and Nutrigenomics)
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Article
Experimental and In Silico Studies on the Development of an Electrochemical Biosensor for the Quantification of H2O2 Based on the ChOx Enzyme
by Elvis Ortiz-Santos, Gabriela Valdés-Ramírez, Cesar Millán-Pacheco, Iris N. Serratos, Maria Luisa Lozano-Camargo, Pablo Dalmasso, Gustavo A. Rivas and Laura Galicia
Biosensors 2025, 15(5), 279; https://doi.org/10.3390/bios15050279 - 29 Apr 2025
Viewed by 936
Abstract
This work presents the development of a biosensing platform for hydrogen peroxide (H2O2) electrochemical reduction. The developed platform uses a multi-walled carbon nanotube paste (PMWCNT) and the enzyme cholesterol oxidase (ChOx). The supramolecular architecture of the PMWCNT/ChOx platform was [...] Read more.
This work presents the development of a biosensing platform for hydrogen peroxide (H2O2) electrochemical reduction. The developed platform uses a multi-walled carbon nanotube paste (PMWCNT) and the enzyme cholesterol oxidase (ChOx). The supramolecular architecture of the PMWCNT/ChOx platform was characterized using cyclic voltammetry, electrochemical impedance spectroscopy, and amperometry. The results indicated that the presence of ChOx enhances the sensitivity of electrochemical detection for H2O2 by 21 times compared to that without ChOx. The designed electrochemical sensing bio-platform for H2O2 shows a sensitivity of 26.15 µA/mM in the linear range from 0.4 to 4.0 mM, an LOD of 0.43 µM, and an LOQ of 1.31 µM. Furthermore, in silico studies (molecular dynamics simulations, molecular docking assays, and binding free energy calculations (ΔGb)) were carried out to characterize and validate the molecular interaction between ChOx and H2O2. The computed data confirmed that the binding is spontaneous, and the type of labile interaction promotes a rapid electrochemical reduction of H2O2. Full article
(This article belongs to the Special Issue Recent Developments in Nanomaterial-Based Electrochemical Biosensors)
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