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Search Results (241)

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Keywords = non-mammalian models

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16 pages, 1760 KiB  
Article
Functional Divergence of NOTCH1 and NOTCH2 in Human Cerebral Organoids Reveals Receptor-Specific Roles in Early Corticogenesis
by Sophia Yakovleva, Anastasia Knyazeva, Anastasia Yunusova, Elina Allayarova, Dmitriy Lanshakov, Anna Malashicheva and Tatiana Shnaider
Int. J. Mol. Sci. 2025, 26(15), 7309; https://doi.org/10.3390/ijms26157309 - 29 Jul 2025
Viewed by 254
Abstract
The Notch signaling pathway is a critical regulator of embryonic brain development. Among its four mammalian receptors, Notch1 and Notch2 are particularly significant in the developing cortex, yet their roles in human neurodevelopment are not well understood. In murine cortex development, Notch1 primarily [...] Read more.
The Notch signaling pathway is a critical regulator of embryonic brain development. Among its four mammalian receptors, Notch1 and Notch2 are particularly significant in the developing cortex, yet their roles in human neurodevelopment are not well understood. In murine cortex development, Notch1 primarily regulates early progenitor identity and neurogenesis, while Notch2 is required for maintaining radial glial cells at later stages. However, it is unclear whether these functions are conserved in the human developing brain. In this study, we used cerebral organoids as an in vitro model of early human corticogenesis and conducted lentiviral shRNA-mediated knockdowns of NOTCH1 and NOTCH2. Our findings indicate that NOTCH1 is essential for organoid growth, lumen morphogenesis, radial glial identity, and progenitor proliferation. In contrast, depleting NOTCH2 did not significantly affect these early developmental processes. These results demonstrate that NOTCH1 and NOTCH2 have potentially non-redundant and temporally distinct roles in early human corticogenesis, reflecting receptor-specific specialization within the Notch signaling pathway. Full article
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23 pages, 2027 KiB  
Article
Effect of Maternal Dietary DHA and Prenatal Stress Mouse Model on Autistic-like Behaviors, Lipid Peroxidation Activity, and GABA Expression in Offspring Pups
by Taeseon Woo, Nick I. Ahmed, Michael K. Appenteng, Candice King, Runting Li, Kevin L. Fritsche, Grace Y. Sun, Jiankun Cui, Matthew J. Will, Sara V. Maurer, Hanna E. Stevens, David Q. Beversdorf and C. Michael Greenlief
Int. J. Mol. Sci. 2025, 26(14), 6730; https://doi.org/10.3390/ijms26146730 - 14 Jul 2025
Viewed by 296
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the most abundant ω-3 fatty acids in the membrane phospholipids of the mammalian brain, and dietary DHA plays an important role in brain development and maintenance of brain structure. In this study, we investigated whether peri-natal supplementation of DHA can alleviate autistic-like behaviors in a genetic risk/stress mouse model and how it alters lipid peroxidation activity and GABAergic system gene expression in the forebrain. Pregnant heterozygous serotonin transporter knockout (SERT-KO) and wild-type (WT) dams were placed in either non-stressed control conditions or chronic variable stress (CVS) conditions and fed either a control diet or a DHA-rich (1% by weight) diet. Offspring of each group were assessed for anxiety and autism-associated behavior at post-natal day 60 using an open field test, elevated plus maze test, repetitive behavior, and the 3-chamber social approach test. A liquid chromatography-mass spectrometry (LC-MS)-based method was used to follow changes in levels of lipid peroxidation products in the cerebral cortex. Male offspring of prenatally stressed SERT-het KO dams exhibited decreased social preference behaviors and increased repetitive grooming behaviors compared to WT control offspring. Moreover, DHA supplementation in male SERT-het mice decreased frequency of grooming behaviors albeit showing no associated effects on social behaviors. Regardless of stress conditions, supplementation of DHA to the WT mice did not result in alterations in grooming nor social interaction in the offspring. Furthermore, no apparent changes were observed in the lipid peroxidation products comparing the stressed and non-stressed brains. Gad2 was downregulated in the cortex of female offspring of prenatally stressed SERT-KO dams, and this change appeared to be rescued by DHA supplementation in offspring. Gad2 was upregulated in the striatum of male offspring of prenatally stressed SERT-KO dams, but DHA did not significantly alter the expression compared to the control diet condition. Full article
(This article belongs to the Collection Feature Papers in Bioactives and Nutraceuticals)
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26 pages, 11210 KiB  
Article
Perspectives on the pH-Influenced Design of Chitosan–Genipin Nanogels for Cell-Targeted Delivery
by Julieta D. Glasman, Agustina Alaimo, Cecilia Samaniego López, María Edith Farías, Romina B. Currá, Diego G. Lamas and Oscar E. Pérez
Pharmaceutics 2025, 17(7), 876; https://doi.org/10.3390/pharmaceutics17070876 - 3 Jul 2025
Viewed by 519
Abstract
Background: Chitosan (CS) crosslinked with genipin (GNP) provides a mild, non-toxic route to generate nanogels (NGs) with enhanced integrity and colloidal stability. Objectives: To develop and characterise CS-GNP NG as a novel platform for targeted cellular delivery, optimising design through physicochemical [...] Read more.
Background: Chitosan (CS) crosslinked with genipin (GNP) provides a mild, non-toxic route to generate nanogels (NGs) with enhanced integrity and colloidal stability. Objectives: To develop and characterise CS-GNP NG as a novel platform for targeted cellular delivery, optimising design through physicochemical characterisation and biocompatibility evaluation. Methods: NGs were synthesised under optimised conditions by adjusting the pH of the CS solution, followed by high-intensity ultrasound (HIUS) to achieve disaggregation. Physicochemical characterisation was carried out using UV-Vis spectroscopy, FTIR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). Rheological studies and SAXS analysis assessed structural properties. Biocompatibility was evaluated via MTT assay, and internalisation was monitored by fluorescence microscopy on mammalian cell lines. Results: NG formation was highly pH-dependent, with optimal configuration at pH 4.5, yielding stable, uniformly sized particles (~200 nm, ζ-potential +29 mV). Kinetic modelling showed a sigmoidal formation pattern, suggesting nucleation, growth, and stabilisation. FTIR confirmed covalent bonding between CS and GNP via primary amide bonds and Schiff bases. Rheology indicated pseudoplastic behaviour, and SAXS revealed a compact network formation. Biocompatibility assays confirmed non-cytotoxicity below 100 µg/mL and efficient cellular uptake. Conclusions: This study presents a rapid, reproducible protocol for generating colloidally stable, biocompatible NGs suitable for drug delivery. Full article
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15 pages, 2063 KiB  
Article
Metabolic Disruptions in Zebrafish Induced by α-Cypermethrin: A Targeted Metabolomics Study
by Hang-Ji Ok, Ji-Woo Yu, Jung-Hoon Lee, Eun-Song Choi, Jong-Hwan Kim, Yoonjeong Jeon, Won Noh, Sung-Gil Choi, Jeong-Han Kim, Min-Ho Song and Ji-Ho Lee
Toxics 2025, 13(7), 529; https://doi.org/10.3390/toxics13070529 - 24 Jun 2025
Viewed by 618
Abstract
The widespread application of pesticides in agriculture has raised increasing concerns regarding their ecological impact, particularly in aquatic environments. Among these, α-cypermethrin, a highly active isomeric form of cypermethrin, has been extensively used due to its potent insecticidal efficacy and low mammalian toxicity. [...] Read more.
The widespread application of pesticides in agriculture has raised increasing concerns regarding their ecological impact, particularly in aquatic environments. Among these, α-cypermethrin, a highly active isomeric form of cypermethrin, has been extensively used due to its potent insecticidal efficacy and low mammalian toxicity. However, its toxicity to non-target aquatic organisms remains insufficiently understood at the metabolic level. In this study, a targeted metabolomics approach was employed to investigate the biochemical effects of α-cypermethrin in adult zebrafish. Acute toxicity was first determined to establish sublethal exposure concentrations (0.15 µg/L and 1.5 µg/L), followed by a 48 h exposure under a controlled flow-through system. GC-MS/MS-based analysis quantified 395 metabolites, and multivariate statistical models (principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA)) revealed clear dose-dependent metabolic alterations at two time points. Pathway analysis identified disruptions in glycolysis, glycerolipid metabolism, amino acid turnover, and glutathione pathways. Notably, glutamate depletion and associated reductions in GABA (4-Aminobutanoate) and TCA (Tricarboxylic acid) cycle intermediates suggest oxidative stress-induced metabolic bottlenecks. These results provide mechanistic insights into α-cypermethrin-induced toxicity and demonstrate the utility of metabolite-level biomarkers for environmental monitoring. This study contributes to a systems-level understanding of how sublethal pesticide exposure affects vertebrate metabolism, offering a basis for improved ecological risk assessment and pesticide regulation. Full article
(This article belongs to the Special Issue Toxic Pollutants and Ecological Risk in Aquatic Environments)
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18 pages, 2189 KiB  
Article
Changes of CB1 Receptor Expression in Tissues of Cocaine-Exposed Eels
by Lorenzo Riccio, Teresa Chianese, Aldo Mileo, Sabrina Balsamo, Rosaria Sciarrillo, Roberta Gatta, Luigi Rosati, Maria De Falco and Anna Capaldo
Animals 2025, 15(12), 1734; https://doi.org/10.3390/ani15121734 - 12 Jun 2025
Viewed by 1069
Abstract
Previous studies performed on the European eel Anguilla anguilla showed changes in the morphology and physiology of several tissues after exposure to environmental cocaine concentrations. To better understand the model through which cocaine produced its effects on these tissues, we investigated whether there [...] Read more.
Previous studies performed on the European eel Anguilla anguilla showed changes in the morphology and physiology of several tissues after exposure to environmental cocaine concentrations. To better understand the model through which cocaine produced its effects on these tissues, we investigated whether there were alterations in the expression of cannabinoid CB1 receptor (CB1R). Indeed, the endocannabinoid system, and CB1R, regulate neurotransmission, neurodevelopment, embryonic development, reproduction, and the activity of the gastrointestinal system. CB1R has been detected in nervous and peripheral tissues in mammals, and orthologues of the mammalian CB1R are found throughout vertebrates including chicken, turtle, frog, and fish. Therefore, samples of gut, kidney, ovary, muscle, liver, skin, and gills from cocaine-exposed and non-exposed eels were processed for routine histology. Immunohistochemical analysis was carried out to evaluate the immunolocalization of the CB1R. Our results showed for the first time (1) the presence of CB1R in the peripheral tissues of the eel, and (2) statistically significant differences in the localization of CB1R in the gut, kidney, ovary, muscle, and liver of the eels exposed to cocaine, compared to controls. These results demonstrate the involvement of CB1R in cocaine effects and suggest its potential role as a biomarker of tissue alteration. Full article
(This article belongs to the Section Aquatic Animals)
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31 pages, 1634 KiB  
Review
Advancements in Peripheral Nerve Injury Research Using Lab Animals
by Natalia A. Pluta, Manuela Gaviria, Casey M. Sabbag and Shauna Hill
Anatomia 2025, 4(2), 8; https://doi.org/10.3390/anatomia4020008 - 23 May 2025
Viewed by 1704
Abstract
Peripheral nerve injuries (PNIs) commonly result from trauma, compression, or iatrogenic causes, leading to functional deficits. Despite the peripheral nervous system’s regenerative capacity, current treatments yield inconsistent outcomes. Basic science and translational research supporting nerve repair remain underdeveloped, partly due to the absence [...] Read more.
Peripheral nerve injuries (PNIs) commonly result from trauma, compression, or iatrogenic causes, leading to functional deficits. Despite the peripheral nervous system’s regenerative capacity, current treatments yield inconsistent outcomes. Basic science and translational research supporting nerve repair remain underdeveloped, partly due to the absence of standardized protocols, limiting reproducibility. Animal models are essential for studying injury mechanisms, repair strategies, and therapeutic development. This review examines commonly used animal models in PNI research, from non-mammalian species to rodents and large mammals. We discuss the relevance of injury types, experimental variables (i.e., age, sex, nerve type), and study design elements (i.e., nerve gap size, injury induction methods). Assessing these models’ strengths and limitations, this review aims to guide researchers in selecting appropriate models that enhance preclinical relevance. It also addresses the need for standardized protocols and future directions for improving PNI research and patient outcomes. Various PNI treatments—including microsurgery, nerve grafts, scaffolds, stem cells, immunomodulators, nerve augmentation strategies, and polyethylene glycol-mediated fusion—have been developed using animal models. These models are essential for driving innovation and translating emerging therapies to improve outcomes across a broad range of peripheral nerve injuries. Full article
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36 pages, 1680 KiB  
Review
Genotoxicity in Unconventional Mammalian Models of Wild, Urban, and Agricultural Ecosystems: A Systematic Review Under the One Health Approach
by Nora Bibiana M. Gorla, Mariela Nieves and Daniela Marisol Ferré
Genes 2025, 16(5), 525; https://doi.org/10.3390/genes16050525 - 29 Apr 2025
Cited by 1 | Viewed by 1233
Abstract
Background/Objectives: This systematic review evaluates unconventional mammalian models from wild, agricultural, and urban/domestic ecosystems for genotoxicity assessment under the One Health framework. Non-human primates (NHPs), cattle, and domestic dogs are analyzed as sentinel species due to their distinct environmental niches, unique human interactions, [...] Read more.
Background/Objectives: This systematic review evaluates unconventional mammalian models from wild, agricultural, and urban/domestic ecosystems for genotoxicity assessment under the One Health framework. Non-human primates (NHPs), cattle, and domestic dogs are analyzed as sentinel species due to their distinct environmental niches, unique human interactions, and species-specific traits. In conjunction with this, evidence is presented about the in vitro use of cells of these mammals for the genotoxicological evaluation of different chemical substances, such as veterinary drugs, environmental pollutants, and pesticides. The synthesis focuses on standardized genetic toxicology assays (e.g., chromosomal aberrations, micronucleus, comet assay) aligned with Organization for Economic Cooperation and Development (OECD) guidelines. Methods: A structured search of international literature identified studies employing OECD-compliant genotoxicity assays in NHPs, cattle, dogs, and others not listed in OECD. Data was categorized by species, assay type, chemical class evaluated, environmental context (wild, agricultural, urban), and merits of the papers. Results: NHPs, despite their phylogenetic proximity to humans, show limited genotoxicity data in contrast to biomedical research, which has been constrained by ethical concerns and fieldwork logistics. Cattle emerge as robust models in agricultural settings due to the abundance of studies on the genotoxic capacity of pesticides, veterinary drug, and environmental biomonitoring, with direct implications for food safety. Domestic dogs are recognized as powerful sentinels for human health due to shared exposomes, physiological similarities (e.g., shorter cancer latency), and reduced lifestyle confounders; however, genotoxicity studies in dogs remain sparse compared to chemical exposure monitoring or cancer research. Conclusions: This review advocates for expanded, integrated use of these models to address genotoxic threats across ecosystems, which would benefit both animal and human health. In the application of biomonitoring studies with sentinel animals, a critical gap persists: the frequent lack of integration between xenobiotic quantification in environmental and biological samples, along with genotoxicity biomarkers evaluation in sentinel populations, which hinders comprehensive environmental risk assessment. Full article
(This article belongs to the Collection Feature Papers in ‘Animal Genetics and Genomics’)
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17 pages, 4041 KiB  
Article
Characterization and Biological Evaluation of Composite Nanofibrous Membranes Prepared from Hemp Salmon (Oncorhynchus keta) Skin Collagen
by Yu Liu, Mochi Zhu, Rui Duan and Junjie Zhang
Cells 2025, 14(7), 537; https://doi.org/10.3390/cells14070537 - 3 Apr 2025
Viewed by 645
Abstract
Aquatic collagen, a natural macromolecule protein with excellent biocompatibility, has attracted attention in the field of medical materials. Compared to mammalian collagen, aquatic collagen offers unique advantages, including the absence of zoonotic disease risks and religious concerns. In this study, salmon skin collagen [...] Read more.
Aquatic collagen, a natural macromolecule protein with excellent biocompatibility, has attracted attention in the field of medical materials. Compared to mammalian collagen, aquatic collagen offers unique advantages, including the absence of zoonotic disease risks and religious concerns. In this study, salmon skin collagen nanofiber membrane (GS) was prepared by electrostatic spinning. Then, skin collagen was combined with silk sericin (SS) and sodium hyaluronate (HA) to fabricate composite collagen nanofiber membrane (GF) using electrostatic spinning technology. GF membranes were further cross-linked (GFL) for use in a mouse wound healing model. The physicochemical properties and biocompatibility of GS, GF, and GFL were evaluated. FTIR analysis revealed that GFL exhibited a more stable secondary structure compared to GS and GF. DSC and TGA results indicated that GFL had the highest thermal stability, followed by GF. Cytotoxicity tests confirmed that GS, GF, and GFL were non-cytotoxic, with GF showing the highest cell viability rate of 175.23 ± 1.77%. In the wound healing model, GFL group achieved nearly complete healing by day 14 (98 ± 0.1%), compared to 76.04 ± 0.01% in the blank group. Measurement of TGF-β1 and VEGF levels in the healing tissue on day 14 indicated that the GFL group had progressed to the late stage of healing, whereas the blank group remained in the early stage. These results suggest that GFL holds significant potential as a medical biomaterial for wound healing applications. Full article
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30 pages, 4603 KiB  
Review
Galleria mellonella as an Invertebrate Model for Studying Fungal Infections
by Gabriel Davi Marena, Luciana Thomaz, Joshua Daniel Nosanchuk and Carlos Pelleschi Taborda
J. Fungi 2025, 11(2), 157; https://doi.org/10.3390/jof11020157 - 18 Feb 2025
Cited by 3 | Viewed by 1831
Abstract
The incidence of fungal infections continues to increase and one of the factors responsible for these high rates is the emergence of multi-resistant species, hospitalizations, inappropriate or prolonged use of medications, and pandemics, such as the ongoing HIV/AIDS pandemic. The recent pandemic caused [...] Read more.
The incidence of fungal infections continues to increase and one of the factors responsible for these high rates is the emergence of multi-resistant species, hospitalizations, inappropriate or prolonged use of medications, and pandemics, such as the ongoing HIV/AIDS pandemic. The recent pandemic caused by the severe acute respiratory syndrome virus (SARS-CoV-2) has led to a significant increase in fungal infections, especially systemic mycoses caused by opportunistic fungi. There is a growing and urgent need to better understand how these microorganisms cause infection and develop resistance as well as to develop new therapeutic strategies to combat the diverse diseases caused by fungi. Non-mammalian hosts are increasingly used as alternative models to study microbial infections. Due to their low cost, simplicity of care, conserved innate immunity and reduced ethical issues, the greater wax moth Galleria mellonella is an excellent model host for studying fungal infections and it is currently widely used to study fungal pathogenesis and develop innovative strategies to mitigate the mycoses studied. G. mellonella can grow at 37 °C, which is similar to the mammalian temperature, and the anatomy of the larvae allows researchers to easily deliver pathogens, biological products, compounds and drugs. The aim of this review is to describe how G. mellonella is being used as a model system to study fungal infections as well as the importance of this model in evaluating the antifungal profile of potential drug candidates or new therapies against fungi. Full article
(This article belongs to the Special Issue Fungal-Nematode-Insect Interactions)
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12 pages, 1670 KiB  
Article
A Simple Technique for Studying the Interaction of Polypropylene-Based Microplastics with Adherent Mammalian Cells Using a Holder
by Magdalena Obłoza, Magdalena Ścibor, Marta Kaczor-Kamińska and Kamil Kamiński
Molecules 2025, 30(3), 516; https://doi.org/10.3390/molecules30030516 - 23 Jan 2025
Viewed by 1048
Abstract
Microplastics pose a great challenge to human health and could prove to be the most dangerous environmental contaminant of the 21st century. The study presented here is an attempt at proposing a new methodology for studying the interaction of microplastics with adherent mammalian [...] Read more.
Microplastics pose a great challenge to human health and could prove to be the most dangerous environmental contaminant of the 21st century. The study presented here is an attempt at proposing a new methodology for studying the interaction of microplastics with adherent mammalian cells using aides. The disposable holders proposed here provide direct contact between microplastics (with a density lower than that of water) and cells in the course of culturing, which is necessary as we postulate the existence of an interaction. Using several microscopic methods (confocal fluorescence microscopy and scanning electron microscopy (SEM)), we have observed that this interaction causes a non-destructive penetration of the cell monolayer and adhesion of microplastics to the cell surface. The Caco-2 cells were used for the experiments. The said cells are the approximation of the digestive system, which, due to the presence of plastics in drinking water, is particularly vulnerable to direct interactions with these contaminants. Model microplastics were obtained by grinding pellets of chemically pure polypropylene. The imaging of cells in both space and on the surface was supplemented by an assay to determine the cell welfare in the studied microplastic-exposed models, which did not show the occurrence of apoptosis or necrosis after a 24 h exposure. Full article
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14 pages, 1650 KiB  
Article
L-Theanine Extends the Lifespan of Caenorhabditis elegans by Reducing the End Products of Advanced Glycosylation
by Zhihang Huang, Haiming Jing, Yan Pan, Hongxia Cai, Wenjing Zhang, Jingyuan Zhu, Nan Zhang, Dan Wu, Wentao Xu, Hexiang Qiu, Huihui Bao, Guojun Li, Junyu Ning, Bo Xian and Shan Gao
Foods 2025, 14(2), 221; https://doi.org/10.3390/foods14020221 - 13 Jan 2025
Cited by 1 | Viewed by 2586
Abstract
L-theanine, a non-protein amino acid naturally occurring in tea leaves, is recognized for its antioxidant, anti-inflammatory, and neuroprotective properties. Despite its known benefits, the mechanisms by which L-theanine influences lifespan extension remain poorly understood. This study investigated the effects of L-theanine on the [...] Read more.
L-theanine, a non-protein amino acid naturally occurring in tea leaves, is recognized for its antioxidant, anti-inflammatory, and neuroprotective properties. Despite its known benefits, the mechanisms by which L-theanine influences lifespan extension remain poorly understood. This study investigated the effects of L-theanine on the lifespan of Caenorhabditis elegans and explored the underlying mechanisms. Our findings indicate that L-theanine significantly diminishes the accumulation of advanced glycation end products (AGEs), which are biomarkers closely linked to aging and age-related diseases. Through an AGE-level analysis, we observed that L-theanine, when administered during early adulthood, notably extended the lifespan of Caenorhabditis elegans under both normal and high-glucose-induced stress conditions. L-theanine enhanced the lifespan under typical conditions and provided protective effects against high-glucose-induced stress. A further analysis demonstrated that L-theanine extends the lifespan of Caenorhabditis elegans by modulating the DAF-2/DAF-16 insulin-like signaling pathway and reducing the accumulation of advanced glycation end products (AGEs). In summary, this study identified L-theanine as a potential anti-aging intervention that extends the lifespan by reducing AGE accumulation and regulating insulin-like signaling pathways. These findings provide new insights for developing anti-aging strategies and lay the groundwork for further research on the potential benefits of L-theanine in mammals. Future studies could explore the molecular mechanisms, test L-theanine in mammalian models, and assess the long-term side effects. Full article
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29 pages, 3951 KiB  
Review
Galleria mellonella (Greater Wax Moth) as a Reliable Animal Model to Study the Efficacy of Nanomaterials in Fighting Pathogens
by Stefania Villani, Matteo Calcagnile, Christian Demitri and Pietro Alifano
Nanomaterials 2025, 15(1), 67; https://doi.org/10.3390/nano15010067 - 3 Jan 2025
Cited by 4 | Viewed by 2505
Abstract
The spread of multidrug-resistant microbes has made it necessary and urgent to develop new strategies to deal with the infections they cause. Some of these are based on nanotechnology, which has revolutionized many fields in medicine. Evaluating the safety and efficacy of these [...] Read more.
The spread of multidrug-resistant microbes has made it necessary and urgent to develop new strategies to deal with the infections they cause. Some of these are based on nanotechnology, which has revolutionized many fields in medicine. Evaluating the safety and efficacy of these new antimicrobial strategies requires testing in animal models before being tested in clinical trials. In this context, Galleria mellonella could represent a valid alternative to traditional mammalian and non-mammalian animal models, due to its low cost, ease of handling, and valuable biological properties to investigate host–pathogen interactions. The purpose of this review is to provide an updated overview of the literature concerning the use of G. mellonella larvae as an animal model to evaluate safety and efficacy of nanoparticles and nanomaterials, particularly, of those that are used or are under investigation to combat microbial pathogens. Full article
(This article belongs to the Section Biology and Medicines)
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18 pages, 1068 KiB  
Review
Current Status of Synthetic Mammalian Embryo Models
by Haneul Kim and Eunhye Kim
Int. J. Mol. Sci. 2024, 25(23), 12862; https://doi.org/10.3390/ijms252312862 - 29 Nov 2024
Cited by 2 | Viewed by 2257
Abstract
Advances in three-dimensional culture technologies have facilitated the development of synthetic embryo models, such as blastoids, through the co-culturing of diverse stem cell types. These in vitro models enable precise investigation of developmental processes, including gastrulation, neurulation, and lineage specification, thereby advancing our [...] Read more.
Advances in three-dimensional culture technologies have facilitated the development of synthetic embryo models, such as blastoids, through the co-culturing of diverse stem cell types. These in vitro models enable precise investigation of developmental processes, including gastrulation, neurulation, and lineage specification, thereby advancing our understanding of early embryogenesis. By providing controllable, ethically viable platforms, they help circumvent the limitations of in vivo mammalian embryo studies and contribute to developing regenerative medicine strategies. Nonetheless, ethical challenges, particularly regarding human applications, persist. Comparative studies across various species—such as mice, humans, non-human primates, and ungulates, like pigs and cattle—offer crucial insights into both species-specific and conserved developmental mechanisms. In this review, we outline the species-specific differences in embryonic development and discuss recent advancements in stem cell and synthetic embryo models. Specifically, we focus on the latest stem cell research involving ungulates, such as pigs and cattle, and provide a comprehensive overview of the improvements in synthetic embryo technology. These insights contribute to our understanding of species-specific developmental biology, help improve model efficiency, and guide the development of new models. Full article
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15 pages, 13962 KiB  
Article
The Role of the Cytoskeletal Regulatory Protein, Mammalian Enabling Protein (Mena), in Invasion and Metastasis of HPV16-Related Oral Squamous Cell Carcinoma
by Zhichen Guo, Linyang Xie, Hao Cui, Xin Yang, Hong Qi, Ming Yu, Yuxin Gong, Junbo Tu and Sijia Na
Cells 2024, 13(23), 1972; https://doi.org/10.3390/cells13231972 - 28 Nov 2024
Viewed by 956
Abstract
Background: The objective of this study was to investigate the effect of mammalian-enabled protein (Mena) on invasion and metastasis of HPV16-related oral squamous cell carcinoma (OSCC) and the underlying mechanism. Materials and methods: The Mena gene expression profile of HPV-related OSCC was analyzed [...] Read more.
Background: The objective of this study was to investigate the effect of mammalian-enabled protein (Mena) on invasion and metastasis of HPV16-related oral squamous cell carcinoma (OSCC) and the underlying mechanism. Materials and methods: The Mena gene expression profile of HPV-related OSCC was analyzed from the TCGA, GEO and TIMER databases. Immunohistochemistry was performed to study Mena, and the expression of invasion and metastasis-related markers and their clinicopathological characteristics. The role of Mena in the biological behavior of OSCC cell lines was assessed through both non-transfected and stably transfected models, analyzing EMT-related markers in vitro. The effect of Mena on HPV16-related OSCC metastasis through immunodeficient mouse model in vivo. Results: Mena expression was significantly decreased in HPV16-positive OSCC, and Mena expression in HPV16-negative OSCC was related with lymphatic metastasis and TNM stages, and E-cadherin, vimentin and MMP-2, but it was not statistically significant in HPV16-positive OSCC. Increased Mena expression was significantly correlated with a poor overall survival and disease-free survival in an HPV16-negative OSCC patient. Mena plays a vital role in promoting OSCC cell migration, invasion and metastasis. Conclusions: Mena promotes OSCC invasion and metastasis in HPV-negative OSCC by activating the EMT process. However, Mena expression in OSCC infected with HPV16 is inhibited, thus suppressing its invasion and metastasis ability. Full article
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24 pages, 5421 KiB  
Article
Rapid Development of Modified Vaccinia Virus Ankara (MVA)-Based Vaccine Candidates Against Marburg Virus Suitable for Clinical Use in Humans
by Alina Tscherne, Georgia Kalodimou, Alexandra Kupke, Cornelius Rohde, Astrid Freudenstein, Sylvia Jany, Satendra Kumar, Gerd Sutter, Verena Krähling, Stephan Becker and Asisa Volz
Vaccines 2024, 12(12), 1316; https://doi.org/10.3390/vaccines12121316 - 24 Nov 2024
Cited by 1 | Viewed by 2318
Abstract
Background/Objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and [...] Read more.
Background/Objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and confirmed human cases outside Africa are, so far, exclusively imported by returning travelers. Over the previous years, MARV has also spread to non-endemic African countries, demonstrating its potential to cause epidemics. Although MARV-specific vaccines are evaluated in preclinical and clinical research, none have been approved for human use. Modified Vaccinia virus Ankara (MVA), a well-established viral vector used to generate vaccines against emerging pathogens, can deliver multiple antigens and has a remarkable clinical safety and immunogenicity record, further supporting its evaluation as a vaccine against MARV. The rapid availability of safe and effective MVA-MARV vaccine candidates would expand the possibilities of multi-factored intervention strategies in endemic countries. Methods: We have used an optimized methodology to rapidly generate and characterize recombinant MVA candidate vaccines that meet the quality requirements to proceed to human clinical trials. As a proof-of-concept for the optimized methodology, we generated two recombinant MVAs that deliver either the MARV glycoprotein (MVA-MARV-GP) or the MARV nucleoprotein (MVA-MARV-NP). Results: Infections of human cell cultures with recombinant MVA-MARV-GP and MVA-MARV-NP confirmed the efficient synthesis of MARV-GP and MARV-NP proteins in mammalian cells, which are non-permissive for MVA replication. Prime-boost immunizations in C57BL/6J mice readily induced circulating serum antibodies binding to recombinant MARV-GP and MARV-NP proteins. Moreover, the MVA-MARV-candidate vaccines elicited MARV-specific T-cell responses in C57BL/6J mice. Conclusions: We confirmed the suitability of our two backbone viruses MVA-mCherry and MVA-GFP in a proof-of-concept study to rapidly generate candidate vaccines against MARV. However, further studies are warranted to characterize the protective efficacy of these recombinant MVA-MARV vaccines in other preclinical models and to evaluate them as vaccine candidates in humans. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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