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21 pages, 1024 KiB  
Review
The Impact of Environmental Factors on the Secretion of Gastrointestinal Hormones
by Joanna Smarkusz-Zarzecka, Lucyna Ostrowska and Marcelina Radziszewska
Nutrients 2025, 17(15), 2544; https://doi.org/10.3390/nu17152544 (registering DOI) - 2 Aug 2025
Abstract
The enteroendocrine system of the gastrointestinal (GI) tract is the largest endocrine organ in the human body, playing a central role in the regulation of hunger, satiety, digestion, and energy homeostasis. Numerous factors—including dietary components, physical activity, and the gut microbiota—affect the secretion [...] Read more.
The enteroendocrine system of the gastrointestinal (GI) tract is the largest endocrine organ in the human body, playing a central role in the regulation of hunger, satiety, digestion, and energy homeostasis. Numerous factors—including dietary components, physical activity, and the gut microbiota—affect the secretion of GI hormones. This study aims to analyze how these factors modulate enteroendocrine function and influence systemic metabolic regulation. This review synthesizes the current scientific literature on the physiology and distribution of enteroendocrine cells and mechanisms of hormone secretion in response to macronutrients, physical activity, and microbial metabolites. Special attention is given to the interactions between gut-derived signals and central nervous system pathways involved in appetite control. Different GI hormones are secreted in specific regions of the digestive tract in response to meal composition and timing. Macronutrients, particularly during absorption, stimulate hormone release, while physical activity influences hormone concentrations, decreasing ghrelin and increasing GLP-1, PYY, and leptin levels. The gut microbiota, through fermentation and metabolite production (e.g., SCFAs and bile acids), modulates enteroendocrine activity. Species such as Akkermansia muciniphila are associated with improved gut barrier integrity and enhanced GLP-1 secretion. These combined effects contribute to appetite regulation and energy balance. Diet composition, physical activity, and gut microbiota are key modulators of gastrointestinal hormone secretion. Their interplay significantly affects appetite regulation and metabolic health. A better understanding of these relationships may support the development of personalized strategies for managing obesity and related disorders. Full article
(This article belongs to the Section Nutritional Immunology)
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18 pages, 5178 KiB  
Article
Quantification of Suspended Sediment Concentration Using Laboratory Experimental Data and Machine Learning Model
by Sathvik Reddy Nookala, Jennifer G. Duan, Kun Qi, Jason Pacheco and Sen He
Water 2025, 17(15), 2301; https://doi.org/10.3390/w17152301 (registering DOI) - 2 Aug 2025
Abstract
Monitoring sediment concentration in water bodies is crucial for assessing water quality, ecosystems, and environmental health. However, physical sampling and sensor-based approaches are labor-intensive and unsuitable for large-scale, continuous monitoring. This study employs machine learning models to estimate suspended sediment concentration using images [...] Read more.
Monitoring sediment concentration in water bodies is crucial for assessing water quality, ecosystems, and environmental health. However, physical sampling and sensor-based approaches are labor-intensive and unsuitable for large-scale, continuous monitoring. This study employs machine learning models to estimate suspended sediment concentration using images captured in natural light, named RGB, and near-infrared (NIR) conditions. A controlled dataset of approximately 1300 images with SSC values ranging from 1000 mg/L to 150,000 mg/L was developed, incorporating temperature, time of image capture, and solar irradiance as additional features. Random forest regression and gradient boosting regression were trained on mean RGB values, red reflectance, time of captured, and temperature for natural light images, achieving up to 72.96% accuracy within a 30% relative error. In contrast, NIR images leveraged gray-level co-occurrence matrix texture features and temperature, reaching 83.08% accuracy. Comparative analysis showed that ensemble models outperformed deep learning models like Convolutional Neural Networks and Multi-Layer Perceptrons, which struggled with high-dimensional feature extraction. These findings suggest that using machine learning models and RGB and NIR imagery offers a scalable, non-invasive, and cost-effective way of sediment monitoring in support of water quality assessment and environmental management. Full article
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23 pages, 8591 KiB  
Article
Targeting Cellular Senescence with Liposome-Encapsulated Fisetin: Evidence of Senomorphic Effect
by Agata Henschke, Bartosz Grześkowiak, Olena Ivashchenko, María Celina Sánchez-Cerviño, Emerson Coy and Sergio Moya
Int. J. Mol. Sci. 2025, 26(15), 7489; https://doi.org/10.3390/ijms26157489 (registering DOI) - 2 Aug 2025
Abstract
Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected [...] Read more.
Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration. Full article
(This article belongs to the Section Molecular Pharmacology)
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26 pages, 7634 KiB  
Article
Research on the Preparation and Performance of Wood with High Negative Oxygen Ion Release Induced by Moisture
by Min Yin, Yuqi Zhang, Yun Lu, Zongying Fu, Haina Mi, Jianfang Yu and Ximing Wang
Coatings 2025, 15(8), 905; https://doi.org/10.3390/coatings15080905 (registering DOI) - 2 Aug 2025
Abstract
With the growing severity of environmental pollution, people are paying increasing attention to their health. However, naturally occurring wood with health benefits and applications in human healthcare is still scarce. Natural wood exhibits a limited negative oxygen ion release capacity, and this release [...] Read more.
With the growing severity of environmental pollution, people are paying increasing attention to their health. However, naturally occurring wood with health benefits and applications in human healthcare is still scarce. Natural wood exhibits a limited negative oxygen ion release capacity, and this release has a short duration, failing to meet practical application requirements. This study innovatively developed a humidity-responsive, healthy wood material with a high negative oxygen ion release capacity based on fast-growing poplar. Through vacuum cyclic impregnation technology, hexagonal stone powder was infused into the pores of poplar wood, endowing it with the ability to continuously release negative oxygen ions. The healthy wood demonstrated a static average negative oxygen ion release rate of 537 ions/cm3 (peaking at 617 ions/cm3) and a dynamic average release rate of 3,170 ions/cm3 (peaking at 10,590 ions/cm3). The results showed that the particle size of hexagonal stone powder in suspension was influenced by the dispersants and dispersion processes. The composite dispersion process demonstrated optimal performance when using 0.5 wt% silane coupling agent γ-(methacryloxy)propyltrimethoxysilane (KH570), achieving the smallest particle size of 8.93 μm. The healthy wood demonstrated excellent impregnation performance, with a weight gain exceeding 14.61% and a liquid absorption rate surpassing 165.18%. The optimal impregnation cycle for vacuum circulation technology was determined to be six cycles, regardless of the type of dispersant. Compared with poplar wood, the hygroscopic swelling rate of healthy wood was lower, especially in PEG-treated samples, where the tangential, radial, longitudinal, and volumetric swelling rates decreased by 70.93%, 71.67%, 69.41%, and 71.35%, respectively. Combining hexagonal stone powder with fast-growing poplar wood can effectively enhance the release of negative oxygen ions. The static average release of negative oxygen ions from healthy wood is 1.44 times that of untreated hexagonal stone powder, and the dynamic release reaches 2 to 3 times the concentration of negative oxygen ions specified by national fresh air standards. The water-responsive mechanism revealed that negative oxygen ion release surged when ambient humidity exceeded 70%. This work proposes a sustainable and effective method to prepare healthy wood with permanent negative oxygen ion release capability. It demonstrates great potential for improving indoor air quality and enhancing human health. Full article
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11 pages, 1083 KiB  
Article
Assessment of 137Cs and 40K Transfer Factors in Croatian Agricultural Systems and Implications for Food Safety
by Tomislav Bituh, Branko Petrinec, Dragutin Hasenay and Sanja Stipičević
Environments 2025, 12(8), 269; https://doi.org/10.3390/environments12080269 (registering DOI) - 2 Aug 2025
Abstract
Croatian agricultural legislation acknowledges the significance of radionuclides as pollutants in agricultural lands; however, it lacks specific thresholds or reference values for contamination levels, in contrast to other contaminants. This absence highlights the necessity for a comprehensive assessment of radionuclides across various agricultural [...] Read more.
Croatian agricultural legislation acknowledges the significance of radionuclides as pollutants in agricultural lands; however, it lacks specific thresholds or reference values for contamination levels, in contrast to other contaminants. This absence highlights the necessity for a comprehensive assessment of radionuclides across various agricultural systems in Croatia. This study investigates the transfer of radionuclides 137Cs and 40K from soil to agricultural crops throughout Croatia and estimates the consequent annual ingestion dose for the population. The samples collected comprised food crops and animal feed, with corresponding soil samples analyzed to calculate transfer factors. Activity concentrations of 137Cs exhibited regional and crop-type variability, reflecting the uneven distribution of fallout and differing soil properties. Transfer factors were found to range from 0.003 to 0.06 for 137Cs and from 0.15 to 3.1 for 40K, with the highest uptake occurring in kidney beans. The total estimated annual effective ingestion dose was calculated to be a maximum of 0.748 mSv/year for children aged 2–7, predominantly attributable to 40K. Given the homeostatic regulation of potassium in the human body, the dose associated with 137Cs poses a more significant radiological concern. These findings underscore the need for radionuclide-specific agricultural legislation in Croatia and offer a baseline for recommending reference values and informing future regulations regarding agricultural soil contamination. Full article
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16 pages, 6744 KiB  
Article
Thermochemical Conversion of Digestate Derived from OFMSW Anaerobic Digestion to Produce Methane-Rich Syngas with CO2 Sorption
by Emanuele Fanelli, Cesare Freda, Assunta Romanelli, Vito Valerio, Adolfo Le Pera, Miriam Sellaro, Giacinto Cornacchia and Giacobbe Braccio
Processes 2025, 13(8), 2451; https://doi.org/10.3390/pr13082451 (registering DOI) - 2 Aug 2025
Abstract
The energetic valorization of digestate obtained from anaerobic digestion (AD) of the organic fraction of municipal solid waste (OFMSW) was investigated via pyrolysis in a bench-scale rotary kiln. The mass rate of dried digestate to the rotary kiln pyrolyzer was fixed at 500 [...] Read more.
The energetic valorization of digestate obtained from anaerobic digestion (AD) of the organic fraction of municipal solid waste (OFMSW) was investigated via pyrolysis in a bench-scale rotary kiln. The mass rate of dried digestate to the rotary kiln pyrolyzer was fixed at 500 gr/h. The effect of the pyrolysis temperature was investigated at 600, 700, and 800 °C. The pyrolysis products, char, oil, and gas, were quantified and chemically analyzed. It was observed that with the increase in the temperature from 600 to 800 °C, the char decreased from 60.3% to 52.2% and the gas increased from 26.5% to 35.3%. With the aim of increasing the methane production and methane concentration in syngas, the effect of CaO addition to the pyrolysis process was investigated at the same temperature, too. The mass ratio CaO/dried digestate was set at 0.2. The addition of CaO sorbent has a clear effect on the yield and composition of pyrolysis products. Under the experimental conditions, CaO was observed to act both as a CO2 sorbent and as a catalyst, promoting cracking and reforming reactions of volatile compounds. In more detail, at the investigated temperatures, a net reduction in CO2 concentration was observed in syngas, accompanied by an increase in CH4 concentration. The gas yield decreased with the CaO addition because of CO2 chemisorption. The oil yield decreased as well, probably because of the cracking and reforming effect of the CaO on the volatiles. A very promising performance of the CaO sorbent was observed at 600 °C; at this temperature, the CO2 concentration decreased from 32.2 to 13.9 mol %, and the methane concentration increased from 16.1 to 29.4 mol %. At the same temperature, the methane production increased from 34 to 63 g/kgdigestate. Full article
(This article belongs to the Section Chemical Processes and Systems)
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33 pages, 12598 KiB  
Article
OKG-ConvGRU: A Domain Knowledge-Guided Remote Sensing Prediction Framework for Ocean Elements
by Renhao Xiao, Yixiang Chen, Lizhi Miao, Jie Jiang, Donglin Zhang and Zhou Su
Remote Sens. 2025, 17(15), 2679; https://doi.org/10.3390/rs17152679 (registering DOI) - 2 Aug 2025
Abstract
Accurate prediction of key ocean elements (e.g., chlorophyll-a concentration, sea surface temperature, etc.) is imperative for maintaining marine ecological balance, responding to marine disaster pollution, and promoting the sustainable use of marine resources. Existing spatio-temporal prediction models primarily rely on either physical or [...] Read more.
Accurate prediction of key ocean elements (e.g., chlorophyll-a concentration, sea surface temperature, etc.) is imperative for maintaining marine ecological balance, responding to marine disaster pollution, and promoting the sustainable use of marine resources. Existing spatio-temporal prediction models primarily rely on either physical or data-driven approaches. Physical models are constrained by modeling complexity and parameterization errors, while data-driven models lack interpretability and depend on high-quality data. To address these challenges, this study proposes OKG-ConvGRU, a domain knowledge-guided remote sensing prediction framework for ocean elements. This framework integrates knowledge graphs with the ConvGRU network, leveraging prior knowledge from marine science to enhance the prediction performance of ocean elements in remotely sensed images. Firstly, we construct a spatio-temporal knowledge graph for ocean elements (OKG), followed by semantic embedding representation for its spatial and temporal dimensions. Subsequently, a cross-attention-based feature fusion module (CAFM) is designed to efficiently integrate spatio-temporal multimodal features. Finally, these fused features are incorporated into an enhanced ConvGRU network. For multi-step prediction, we adopt a Seq2Seq architecture combined with a multi-step rolling strategy. Prediction experiments for chlorophyll-a concentration in the eastern seas of China validate the effectiveness of the proposed framework. The results show that, compared to baseline models, OKG-ConvGRU exhibits significant advantages in prediction accuracy, long-term stability, data utilization efficiency, and robustness. This study provides a scientific foundation and technical support for the precise monitoring and sustainable development of marine ecological environments. Full article
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20 pages, 2076 KiB  
Article
Numerical Modeling of Gentamicin Transport in Agricultural Soils: Implications for Environmental Pollution
by Nami Morales-Durán, Sebastián Fuentes, Jesús García-Gallego, José Treviño-Reséndez, Josué D. García-Espinoza, Rubén Morones-Ramírez and Carlos Chávez
Antibiotics 2025, 14(8), 786; https://doi.org/10.3390/antibiotics14080786 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives: In recent years, the discharge of antibiotics into rivers and irrigation canals has increased. However, few studies have addressed the impact of these compounds on agricultural fields that use such water to meet crop demands. Methods: In this study, the transport of [...] Read more.
Background/Objectives: In recent years, the discharge of antibiotics into rivers and irrigation canals has increased. However, few studies have addressed the impact of these compounds on agricultural fields that use such water to meet crop demands. Methods: In this study, the transport of two types of gentamicin (pure gentamicin and gentamicin sulfate) was modeled at concentrations of 150 and 300 μL/L, respectively, in a soil with more than 60 years of agricultural use. Infiltration tests under constant head conditions and gentamicin transport experiments were conducted in acrylic columns measuring 14 cm in length and 12.7 cm in diameter. The scaling parameters for the Richards equation were obtained from experimental data, while those for the advection–dispersion equation were estimated using inverse methods through a nonlinear optimization algorithm. In addition, a fractal-based model for saturated hydraulic conductivity was employed. Results: It was found that the dispersivity of gentamicin sulfate is 3.1 times higher than that of pure gentamicin. Based on the estimated parameters, two simulation scenarios were conducted: continuous application of gentamicin and soil flushing after antibiotic discharge. The results show that the transport velocity of gentamicin sulfate in the soil may have short-term consequences for the emergence of resistant microorganisms due to the destination of wastewater containing antibiotic residues. Conclusions: Finally, further research is needed to evaluate the impact of antibiotics on soil physical properties, as well as their effects on irrigated crops, animals that consume such water, and the soil microbiota. Full article
(This article belongs to the Special Issue Impact of Antibiotic Residues in Wastewater)
23 pages, 4116 KiB  
Article
A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations
by Hanne Devos, Ioanna K. Mina, Foteini Paradeisi, Manousos Makridakis, Aggeliki Tserga, Marika Mokou, Jerome Zoidakis, Harald Mischak, Antonia Vlahou, Agnieszka Latosinska and Maria G. Roubelakis
Int. J. Mol. Sci. 2025, 26(15), 7480; https://doi.org/10.3390/ijms26157480 (registering DOI) - 2 Aug 2025
Abstract
Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of [...] Read more.
Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of nine most abundant, naturally occurring urinary COL(I)-derived peptides on human endothelial cells at physiological concentrations, using cell migration assays, mass spectrometry-based proteomics, flow cytometry, and AlphaFold 3. While none of the peptides significantly altered endothelial migration by themselves at physiological concentrations, full-length COL(I) increased cell migration, which was inhibited by Peptide 1 (229NGDDGEAGKPGRPGERGPpGp249). This peptide uniquely contains the DGEA and GRPGER motifs, interacting with integrin α2β1. Flow cytometry confirmed the presence of integrin α2β1 on human endothelial cells, and AlphaFold 3 modeling predicted an interaction between Peptide 1 and integrin α2. Mass spectrometry-based proteomics investigating signaling pathways revealed that COL(I) triggered phosphorylation events linked to integrin α2β1 activation and cell migration, which were absent in COL(I) plus peptide 1-treated cells. These findings identify Peptide 1 as a biologically active COL(I)-derived peptide at a physiological concentration capable of modulating collagen-induced cell migration, and provide a foundation for further investigation into its mechanisms of action and role in urine excretion. Full article
16 pages, 562 KiB  
Article
Investigation of Effects of Low Ruminal pH Values on Serum Concentrations of Macrominerals, Trace Elements, and Vitamins and Oxidative Status of Dairy Cows
by Panagiotis D. Katsoulos, Bengü Bilgiç, Duygu Tarhan, Fatma Ateş, Suat Ekin, Süleyman Kozat, Banu Dokuzeylül, Mehmet Erman Or, Emmanouil Kalaitzakis, Georgios E. Valergakis and Nikolaos Panousis
Ruminants 2025, 5(3), 35; https://doi.org/10.3390/ruminants5030035 (registering DOI) - 2 Aug 2025
Abstract
Due to the feeding system (high-concentrate diet) during the early lactation stage, ruminal pH in dairy cows follows a diurnal pattern and can remain below the critical level of 5.5 for extended periods of the day. This study aimed to evaluate the effect [...] Read more.
Due to the feeding system (high-concentrate diet) during the early lactation stage, ruminal pH in dairy cows follows a diurnal pattern and can remain below the critical level of 5.5 for extended periods of the day. This study aimed to evaluate the effect of low ruminal pH on blood concentrations of certain macrominerals, trace minerals, and fat-soluble vitamins and on the oxidative status of dairy cows during the first half of lactation. Fifty-three randomly selected lactating Holstein cows were used; blood and ruminal fluid samples were collected from all cows on days 30, 90 and 150 of lactation. Blood samples were obtained via coccygeal venipuncture, while the ruminal fluid was obtained by rumenocentesis and the pH was measured immediately after collection. Using a threshold pH of 5.5, samples were classified as normal (pH > 5.5) or low pH (pH ≤ 5.5). Serum concentrations of Ca, Mg, K, Cr, Mn, Zn, Se, and vitamins A, D3, E, and K were not significantly affected by ruminal pH, either by days in milk or by their interaction (p > 0.05). Plasma malondialdehyde and reduced glutathione followed the same trend (p > 0.05). Copper concentration was significantly higher (p < 0.05), and Fe concentration tended to be higher in cows with low pH compared to those with normal pH (p = 0.052). On day 150 of lactation, Cu, Fe, and Co concentrations were significantly higher in low-pH cows compared to normal-pH cows (p < 0.05). Low ruminal pH is associated with significant changes in serum concentrations of copper, iron, and cobalt but has no significant effect on the oxidative status of the animals or on the serum concentrations of the macro elements and fat-soluble vitamins studied. Full article
21 pages, 1705 KiB  
Article
Antioxidant Effects of Exogenous Mitochondria: The Role of Outer Membrane Integrity
by Sadab Sipar Ibban, Jannatul Naima, Ryo Kato, Taichi Kuroda and Yoshihiro Ohta
Antioxidants 2025, 14(8), 951; https://doi.org/10.3390/antiox14080951 (registering DOI) - 2 Aug 2025
Abstract
The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but [...] Read more.
The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but differing in outer membrane integrity. To evaluate their stability in extracellular conditions, we examined their behavior in serum. Both types underwent mitochondrial permeability transition to a similar extent; however, under intracellular-like conditions after serum incubation, mitochondria with intact membranes retained more polarized mitochondria. Notably, mitochondria with intact outer membranes were internalized more efficiently than those with damaged membranes. In H9c2 cells, both types of mitochondria similarly increased intracellular ATP levels 1 h after administration under all tested conditions. When co-administered with H2O2, both suppressed oxidative damage to a comparable degree, as indicated by similar H2O2-scavenging activity in solution, comparable intracellular ROS levels, and equivalent preservation of electron transport chain activity. However, at higher H2O2 concentrations, cells treated with mitochondria possessing intact outer membranes exhibited greater survival 24 h after co-administration. Furthermore, when mitochondria were added after H2O2-induced damage and their removal, intact mitochondria conferred superior cell survival compared to damaged ones. These findings suggest that while both mitochondrial types exert comparable antioxidant effects, outer membrane integrity prior to administration plays a critical role in enhancing cell survival under conditions of oxidative stress. Full article
(This article belongs to the Section ROS, RNS and RSS)
20 pages, 4612 KiB  
Article
Effect of a Gluten-Free Diet on the Intestinal Microbiota of Women with Celiac Disease
by M. Mar Morcillo Serrano, Paloma Reche-Sainz, Daniel González-Reguero, Marina Robas-Mora, Rocío de la Iglesia, Natalia Úbeda, Elena Alonso-Aperte, Javier Arranz-Herrero and Pedro A. Jiménez-Gómez
Antibiotics 2025, 14(8), 785; https://doi.org/10.3390/antibiotics14080785 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, [...] Read more.
Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article
(This article belongs to the Special Issue Antibiotic Resistance: A One-Health Approach, 2nd Edition)
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24 pages, 6999 KiB  
Article
Plasmid DNA Delivery to Cancer Cells with Poly(L-lysine)-Based Copolymers Bearing Thermally Sensitive Segments: Balancing Polyplex Tightness, Transfection Efficiency, and Biocompatibility
by Mustafa Kotmakci, Natalia Toncheva-Moncheva, Sahar Tarkavannezhad, Bilge Debelec Butuner, Ivaylo Dimitrov and Stanislav Rangelov
Pharmaceutics 2025, 17(8), 1012; https://doi.org/10.3390/pharmaceutics17081012 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) [...] Read more.
Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)77-graft-(PEG)9-block-(PLL)z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)77-graft-(PEG)9-block-(PLL)20) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)77-graft-(PEG)9-block-(PLL)z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article
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20 pages, 489 KiB  
Article
Development of Preliminary Candidate Surface Guidelines for Air Force-Relevant Dermal Sensitizers Using New Approach Methodologies
by Andrew J. Keebaugh, Megan L. Steele, Argel Islas-Robles, Jakeb Phillips, Allison Hilberer, Kayla Cantrell, Yaroslav G. Chushak, David R. Mattie, Rebecca A. Clewell and Elaine A. Merrill
Toxics 2025, 13(8), 660; https://doi.org/10.3390/toxics13080660 (registering DOI) - 2 Aug 2025
Abstract
Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may [...] Read more.
Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may experience ACD at elevated rates compared to other occupations. We aimed to better understand the utility of non-animal testing methods in characterizing the sensitization potential of chemicals used during Air Force operations by evaluating the skin sensitization hazard of Air Force-relevant chemicals using new approach methodologies (NAMs) in a case study. We also evaluated the use of NAM data to develop preliminary candidate surface guidelines (PCSGs, maximum concentrations of chemicals on workplace surfaces to prevent induction of dermal sensitization) for chemicals identified as sensitizers. NAMs for assessing skin sensitization, including in silico models and experimental assays, were leveraged into an integrated approach to predict sensitization hazard for 19 chemicals. Local lymph node assay effective concentration values were predicted from NAM assay data via previously published quantitative models. The derived values were used to calculate PCSGs, which can be used to compare the presence of these chemicals on work surfaces to better understand the risk of Airmen developing ACD from occupational exposures. Full article
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16 pages, 703 KiB  
Article
Retinoic Acid Profiles in Proliferative Verrucous Versus Homogeneous Leukoplakia: A Preliminary Nested Case–Control Study
by Cintia M. Chamorro-Petronacci, Alba Pérez-Jardón, Susana B. Bravo, Pilar Gándara-Vila, Andrés Blanco-Carrión, Yajaira Vanessa Avila-Granizo, Alejandro I. Lorenzo-Pouso, Sara A. Prieto-Barros and Mario Pérez-Sayáns
Biomedicines 2025, 13(8), 1881; https://doi.org/10.3390/biomedicines13081881 (registering DOI) - 2 Aug 2025
Abstract
Background: Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) remain challenging entities due to the absence of reliable prognostic biomarkers. All-trans retinoic acid (atRA), a pivotal modulator of epithelial differentiation and mucosal integrity, has been proposed as a candidate biomarker. This study [...] Read more.
Background: Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) remain challenging entities due to the absence of reliable prognostic biomarkers. All-trans retinoic acid (atRA), a pivotal modulator of epithelial differentiation and mucosal integrity, has been proposed as a candidate biomarker. This study sought to quantify plasma RA levels in patients with OL and PVL compared to healthy controls, assessing their potential clinical utility. Methods: A cohort of 40 participants was recruited, comprising 10 patients with OL, 10 with PVL, and 20 healthy controls. This nested case–control study was derived from previously characterized institutional databases of oral potentially malignant disorders. Plasma samples were analyzed for atRA concentration using high-precision mass spectrometry. Statistical comparisons were conducted to evaluate differences between groups and associations with clinical outcomes. Results: Patients with homogeneous OL exhibited significantly reduced plasma atRA concentrations (mean 2.17 ± 0.39 pg/mL) relative to both PVL patients (2.64 ± 0.56 pg/mL) and healthy controls (2.66 ± 0.92 pg/mL), with p-values of 0.009 and 0.039, respectively. No statistically significant difference was found between PVL patients and controls. Furthermore, atRA levels demonstrated no correlation with clinicopathological variables or malignant progression within the PVL cohort. Conclusions: These preliminary findings indicate that diminished plasma atRA levels may serve as a prognostic marker for homogeneous oral leukoplakia, whilst its role in PVL appears limited. However, effect estimates were imprecise, and additional studies are warranted. Full article
(This article belongs to the Special Issue Cellular and Pathogenesis Mechanisms in Oral Cancer)
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