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18 pages, 5124 KiB  
Article
Effects of Different Drying Methods on the Quality of Forest Ginseng Revealed Based on Metabolomics and Enzyme Activity
by Junjia Xing, Xue Li, Wenyu Dang, Limin Yang, Lianxue Zhang, Wei Li, Yan Zhao, Jiahong Han and Enbo Cai
Foods 2025, 14(15), 2753; https://doi.org/10.3390/foods14152753 - 7 Aug 2025
Abstract
Forest ginseng (FG) is a rare medicinal and culinary plant in China, and its drying quality is heavily dependent on the drying method. This study investigated the effects of traditional hot air drying (HAD) and the self-developed negative-pressure circulating airflow-assisted desiccator drying (PCAD) [...] Read more.
Forest ginseng (FG) is a rare medicinal and culinary plant in China, and its drying quality is heavily dependent on the drying method. This study investigated the effects of traditional hot air drying (HAD) and the self-developed negative-pressure circulating airflow-assisted desiccator drying (PCAD) method on the quality of FG using metabolomics and enzyme activity. The results revealed that the enzyme activities of dried FG were reduced considerably. PCAD preserved higher enzyme activity than HAD. Metabolomics data demonstrate that HAD promotes the formation of primary metabolites (amino acids, lipids, nucleotides, etc.), whereas PCAD promotes the formation of secondary metabolites (terpenoids, phenolic acids, etc.). A change-transformation network was built by combining the metabolites listed above and their biosynthetic pathways, and it was discovered that these biosynthetic pathways were primarily associated with the mevalonate (MVA) pathway, lipid metabolism, phenylpropane biosynthesis, and nucleotide metabolism. It is also believed that these findings are related to the chemical stimulation induced by thermal degradation and the ongoing catalysis of enzyme responses to drought stress. The facts presented above will give a scientific basis for the selection of FG drying processes, as well as helpful references for increasing the nutritional quality of processed FG. Full article
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14 pages, 1897 KiB  
Article
Type I Interferon-Enhancing Effect of Cardamom Seed Extract via Intracellular Nucleic Acid Sensor Regulation
by Abdullah Al Sufian Shuvo, Masahiro Kassai and Takeshi Kawahara
Foods 2025, 14(15), 2744; https://doi.org/10.3390/foods14152744 - 6 Aug 2025
Abstract
The induction of type I interferon (IFN) via intracellular nucleic acid sensors may be useful in preventing viral infections. However, little is known about the effect of natural plant materials on sensor responses. We previously found that cardamom (Elettaria cardamomum (L.) Maton) [...] Read more.
The induction of type I interferon (IFN) via intracellular nucleic acid sensors may be useful in preventing viral infections. However, little is known about the effect of natural plant materials on sensor responses. We previously found that cardamom (Elettaria cardamomum (L.) Maton) seed extract (CSWE) enhanced type I IFN expression and prevented influenza virus infection. In this study, we investigated the effect of CSWE on type I IFN responses using intracellular nucleic acid sensor molecules. Human lung epithelial A549 cells were treated with CSWE and transfected with poly(dA:dT) or poly(I:C) using lipofection. CSWE and 1,8-cineole, the major CSWE components, dose-dependently induced type I IFNs and IFN-stimulated genes in both poly(dA:dT)- and poly(I:C)-transfected A549 cells. The type I IFN-enhancing effect of CSWE was dependent on the stimulator of interferon genes (STING), whereas the effect of 1,8-cineole was independent of STING and mediated by the down-regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase expression. Our study suggests that CSWE has the potential to act as a beneficial antiviral agent by enhancing homeostatic type I IFN production. Full article
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25 pages, 8901 KiB  
Article
Purified Cornel Iridoid Glycosides Attenuated Oxidative Stress Induced by Cerebral Ischemia-Reperfusion Injury via Morroniside and Loganin Targeting Nrf2/NQO-1/HO-1 Signaling Pathway
by Zhaoyang Wang, Fangli Xue, Enjie Hu, Yourui Wang, Huiliang Li and Boling Qiao
Cells 2025, 14(15), 1205; https://doi.org/10.3390/cells14151205 - 6 Aug 2025
Abstract
Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and [...] Read more.
Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H2O2-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H2O2-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article
(This article belongs to the Section Cell Signaling)
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13 pages, 3914 KiB  
Article
Biomechanical Analysis of Different Pacifiers and Their Effects on the Upper Jaw and Tongue
by Luca Levrini, Luigi Paracchini, Luigia Ricci, Maria Sparaco, Stefano Saran and Giulia Mulè
Appl. Sci. 2025, 15(15), 8624; https://doi.org/10.3390/app15158624 (registering DOI) - 4 Aug 2025
Viewed by 155
Abstract
Aim: Pacifiers play a critical role in the early stages of craniofacial and palate development during infancy. While they provide comfort and aid in soothing, their use can also have significant impacts on the growth and function of the oral cavity. This study [...] Read more.
Aim: Pacifiers play a critical role in the early stages of craniofacial and palate development during infancy. While they provide comfort and aid in soothing, their use can also have significant impacts on the growth and function of the oral cavity. This study aimed to simulate and predict the behavior of six different types of pacifiers and their functional interaction with the tongue and palate, with the goal of understanding their potential effects on orofacial growth and development. Materials and Methods: Biomechanical analysis using Finite Element Analysis (FEA) mathematical models was employed to evaluate the behavior of six different commercial pacifiers in contact with the palate and tongue. Three-dimensional solid models of the palate and tongue were based on the mathematical framework from a 2007 publication. This allowed for a detailed investigation into how various pacifier designs interact with soft and hard oral tissues, particularly the implications on dental and skeletal development. Results: The findings of this study demonstrate that pacifiers exhibit different interactions with the oral cavity depending on their geometry. Anatomical–functional pacifiers, for instance, tend to exert lateral compressions near the palatine vault, which can influence the hard palate and contribute to changes in craniofacial growth. In contrast, other pacifiers apply compressive forces primarily in the anterior region of the palate, particularly in the premaxilla area. Furthermore, the deformation of the tongue varied significantly across different pacifier types: while some pacifiers caused the tongue to flatten, others allowed it to adapt more favorably by assuming a concave shape. These variations highlight the importance of selecting a pacifier that aligns with the natural development of both soft and hard oral tissues. Conclusions: The results of this study underscore the crucial role of pacifier geometry in shaping both the palate and the tongue. These findings suggest that pacifiers have a significant influence not only on facial bone growth but also on the stimulation of oral functions such as suction and feeding. The geometry of the pacifier affects the soft tissues (tongue and muscles) and hard tissues (palate and jaw) differently, which emphasizes the need for careful selection of pacifiers during infancy. Choosing the right pacifier is essential to avoid potential negative effects on craniofacial development and to ensure that the benefits of proper oral function are maintained. Therefore, healthcare professionals and parents should consider these biomechanical factors when introducing pacifiers to newborns. Full article
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17 pages, 972 KiB  
Article
SARS-CoV-2 Main Protease Dysregulates Hepatic Insulin Signaling and Glucose Uptake: Implications for Post-COVID-19 Diabetogenesis
by Praise Tatenda Nhau, Mlindeli Gamede, Andile Khathi and Ntethelelo Sibiya
Pathophysiology 2025, 32(3), 39; https://doi.org/10.3390/pathophysiology32030039 - 4 Aug 2025
Viewed by 129
Abstract
Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, [...] Read more.
Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (Mpro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of Mpro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of Mpro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 Mpro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the Mpro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under Mpro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 Mpro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article
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23 pages, 5771 KiB  
Article
Photobiomodulation of 450 nm Blue Light on Human Keratinocytes, Fibroblasts, and Endothelial Cells: An In Vitro and Transcriptomic Study on Cells Involved in Wound Healing and Angiogenesis
by Jingbo Shao, Sophie Clément, Christoph Reissfelder, Patrick Téoule, Norbert Gretz, Feng Guo, Sabina Hajizada, Stefanie Uhlig, Katharina Mößinger, Carolina de la Torre, Carsten Sticht, Vugar Yagublu and Michael Keese
Biomedicines 2025, 13(8), 1876; https://doi.org/10.3390/biomedicines13081876 - 1 Aug 2025
Viewed by 191
Abstract
Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human [...] Read more.
Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm2) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm2) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article
(This article belongs to the Section Cell Biology and Pathology)
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30 pages, 919 KiB  
Systematic Review
Advances in Research on Brain Structure and Activation Characteristics in Patients with Anterior Cruciate Ligament Reconstruction: A Systematic Review
by Jingyi Wang, Yaxiang Jia, Qiner Li, Longhui Li, Qiuyu Dong and Quan Fu
Brain Sci. 2025, 15(8), 831; https://doi.org/10.3390/brainsci15080831 - 1 Aug 2025
Viewed by 137
Abstract
Objectives: To synthesize evidence on structural and functional neuroplasticity in patients after anterior cruciate ligament reconstruction (ACLR) and its clinical implications. Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, a literature search was conducted using PubMed, Embase, Web of [...] Read more.
Objectives: To synthesize evidence on structural and functional neuroplasticity in patients after anterior cruciate ligament reconstruction (ACLR) and its clinical implications. Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, a literature search was conducted using PubMed, Embase, Web of Science, Scopus, and Cochrane CENTRAL (2018–2025) using specific keyword combinations, screening the results based on predetermined inclusion and exclusion criteria. Results: Among the 27 included studies were the following: (1) sensory cortex reorganization with compensatory visual dependence (5 EEG/fMRI studies); (2) reduced motor cortex efficiency evidenced by elevated AMT (TMS, 8 studies) and decreased γ-CMC (EEG, 3 studies); (3) progressive corticospinal tract degeneration (increased radial diffusivity correlating with postoperative duration); (4) enhanced sensory-visual integration correlated with functional recovery. Conclusions: This review provides a novel synthesis of evidence from transcranial magnetic stimulation (TMS), electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), diffusion tensor imaging (DTI), and functional magnetic resonance imaging (fMRI) studies. It delineates characteristic patterns of post-ACLR structural and functional neural reorganization. Targeting visual–cognitive integration and corticospinal facilitation may optimize rehabilitation. Full article
(This article belongs to the Special Issue Diagnosis, Therapy and Rehabilitation in Neuromuscular Diseases)
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10 pages, 1973 KiB  
Communication
Pro-Angiogenic Effects of Canine Platelet-Rich Plasma: In Vitro and In Vivo Evidence
by Seong-Won An and Young-Sam Kwon
Animals 2025, 15(15), 2260; https://doi.org/10.3390/ani15152260 - 1 Aug 2025
Viewed by 149
Abstract
Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo [...] Read more.
Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article
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15 pages, 1243 KiB  
Review
1-42 Oligomer Injection Model: Understanding Neural Dysfunction and Contextual Memory Deficits in Dorsal CA1
by Min-Kaung-Wint-Mon and Dai Mitsushima
J. Dement. Alzheimer's Dis. 2025, 2(3), 25; https://doi.org/10.3390/jdad2030025 - 1 Aug 2025
Viewed by 91
Abstract
The transgenic animals have been yielding invaluable insights into amyloid pathology by replicating the key features of Alzheimer’s disease (AD). However, there is no clear relationship between senile plaques and memory deficits. Instead, cognitive impairment and synaptic dysfunction are particularly linked to a [...] Read more.
The transgenic animals have been yielding invaluable insights into amyloid pathology by replicating the key features of Alzheimer’s disease (AD). However, there is no clear relationship between senile plaques and memory deficits. Instead, cognitive impairment and synaptic dysfunction are particularly linked to a rise in Aβ1-42 oligomer level. Thus, injection of Aβ1-42 oligomers into a specific brain region is considered an alternative approach to investigate the effects of increased soluble Aβ species without any plaques, offering higher controllability, credibility and validity compared to the transgenic model. The hippocampal CA1 (cornu ammonis 1) region is selectively affected in the early stage of AD and specific targeting of CA1 region directly links Aβ oligomer-related pathology with memory impairment in early AD. Next, the inhibitory avoidance (IA) task, a learning paradigm to assess the synaptic basis of CA1-dependent contextual learning, triggers training-dependent synaptic plasticity similar to in vitro HFS (high-frequency stimulation). Given its reliability in assessing contextual memory and synaptic plasticity, this task provides an effective framework for studying early stage AD-related memory deficit. Therefore, in this review, we will focus on why Aβ1-42 oligomer injection is a valid in vivo model to investigate the early stage of AD and why dorsal CA1 region serves as a target area to understand the adverse effects of Aβ1-42 oligomers on contextual learning through the IA task. Full article
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13 pages, 1623 KiB  
Article
Effect of Absolute Ethanol and Thermal Treatment on Shrinkage and Mechanical Properties of TPU Electrospun Nanofiber Membranes
by Lei Wang, Ming Kong, Shengchun Wang, Chunsheng Li and Min Yang
Coatings 2025, 15(8), 897; https://doi.org/10.3390/coatings15080897 (registering DOI) - 1 Aug 2025
Viewed by 177
Abstract
Thermoplastic polyurethane (TPU) electrospun fiber membranes possess unique micro-nano structures and excellent properties. Adjusting their wettability enables the directional transportation of lubricants. A conventional method for adjusting porosity and wettability involves inducing membrane shrinkage using absolute ethanol and heat treatment. However, the shrinkage [...] Read more.
Thermoplastic polyurethane (TPU) electrospun fiber membranes possess unique micro-nano structures and excellent properties. Adjusting their wettability enables the directional transportation of lubricants. A conventional method for adjusting porosity and wettability involves inducing membrane shrinkage using absolute ethanol and heat treatment. However, the shrinkage response and the corresponding changes in the tensile properties of TPU fiber membranes after induction remain unclear, limiting their applications. Thus, in this study, after being peeled off, the samples were first left to stand at room temperature (RT) for 24 h to release residual stress and stabilize their dimensions, and then treated with dehydrated ethanol at RT and high temperature, respectively, with their shrinkage behaviors observed and recorded. The results showed that TPU nanofiber membranes shrank significantly in absolute ethanol, and the degree of shrinkage was temperature-dependent. The shrinkage rates were 2% and 4% in dehydrated ethanol at room temperature and high temperature, respectively, and heating increased the shrinkage effect by 200%. These findings prove that absolute ethanol causes TPU fibers to shrink, and high temperatures further promote shrinkage. However, although the strong synergistic effect of heat and solvent accelerates shrinkage, it may induce internal structural defects, resulting in the deterioration of mechanical properties. The contraction response induced by anhydrous ethanol stimulation can be used to directionally adjust the local density and modulus of TPU nanofiber membranes, thereby changing the wettability. This approach provides new opportunities for applications in areas such as medium transportation and interface friction reduction in lubrication systems. Full article
(This article belongs to the Section Surface Characterization, Deposition and Modification)
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23 pages, 658 KiB  
Article
Green Innovation Quality in Center Cities and Economic Growth in Peripheral Cities: Evidence from the Yangtze River Delta Urban Agglomeration
by Sijie Duan, Hao Chen and Jie Han
Systems 2025, 13(8), 642; https://doi.org/10.3390/systems13080642 - 1 Aug 2025
Viewed by 261
Abstract
Improving the green innovation quality (GIQ) of center cities is crucial to achieve sustainable urban agglomeration development. Utilizing data on green patent citations and economic indicators across cities in the Yangtze River Delta urban agglomeration (YRD) from 2003 to 2022, this research examines [...] Read more.
Improving the green innovation quality (GIQ) of center cities is crucial to achieve sustainable urban agglomeration development. Utilizing data on green patent citations and economic indicators across cities in the Yangtze River Delta urban agglomeration (YRD) from 2003 to 2022, this research examines the influence of center cities’ GIQ on the economic performance of peripheral municipalities. The results show the following: (1) Center cities’ GIQ exerts a significant suppressive effect on peripheral cities’ economic growth overall. Heterogeneity analysis uncovers a distance-dependent duality. GIQ stimulates growth in proximate cities (within 300 km) but suppresses it beyond this threshold. This spatial siphoning effect is notably amplified in national-level center cities. (2) Mechanisms suggest that GIQ accelerates the outflow of skilled labor in peripheral cities through factor agglomeration and industry transfer mechanisms. Concurrently, it impedes the gradient diffusion of urban services, collectively hindering peripheral development. (3) Increased government green attention (GGA) and industry–university–research cooperation (IURC) in centers can mitigate these negative impacts. This paper contributes to the theoretical discourse on center cities’ spatial externalities within agglomerations and offers empirical support and policy insights for the exertion of spillover effects of high-quality green innovation from center cities and the sustainable development of urban agglomeration. Full article
(This article belongs to the Section Systems Practice in Social Science)
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18 pages, 5008 KiB  
Article
Enhanced Modulation of CaMKII in Mouse Hippocampus by an Antidepressant-like Dose of Melatonin/Ketamine Combination
by Armida Miranda-Riestra, Rosa Estrada-Reyes, Luis A. Constantino-Jonapa, Jesús Argueta, Julián Oikawa-Sala, Miguel A. Reséndiz-Gachús, Daniel Albarrán-Gaona and Gloria Benítez-King
Cells 2025, 14(15), 1187; https://doi.org/10.3390/cells14151187 - 1 Aug 2025
Viewed by 307
Abstract
Forty per cent of major depression patients are resistant to antidepressant medication. Thus, it is necessary to search for alternative treatments. Melatonin (N-acetyl-5-hydroxytryptamine) enhances neurogenesis and neuronal survival in the adult mouse hippocampal dentate gyrus. Additionally, melatonin stimulates the activity of [...] Read more.
Forty per cent of major depression patients are resistant to antidepressant medication. Thus, it is necessary to search for alternative treatments. Melatonin (N-acetyl-5-hydroxytryptamine) enhances neurogenesis and neuronal survival in the adult mouse hippocampal dentate gyrus. Additionally, melatonin stimulates the activity of Ca2+/Calmodulin-dependent Kinase II (CaMKII), promoting dendrite formation and neurogenic processes in human olfactory neuronal precursors and rat organotypic cultures. Similarly, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, modulates CaMKII activity. Importantly, co-treatment of low doses of ketamine (10−7 M) in combination with melatonin (10−7 M) produces additive effects on neurogenic responses in olfactory neuronal precursors. Importantly, enhanced neurogenic responses are produced by conventional antidepressants like ISSRs. The goal of this study was to investigate whether hippocampal CaMKII participates in the signaling pathway elicited by combining doses of melatonin with ketamine acutely administered to mice, 30 min before being subjected to the forced swimming test. The results showed that melatonin, in conjunction with ketamine, significantly enhances CaMKII activation and changes its subcellular distribution in the dentate gyrus of the hippocampus. Remarkably, melatonin causes nuclear translocation of the active form of CaMKII. Luzindole, a non-selective MT1 and MT2 receptor antagonist, abolished these effects, suggesting that CaMKII is downstream of the melatonin receptor pathway that causes the antidepressant-like effects. These findings provide molecular insights into the combined effects of melatonin and ketamine on neuronal plasticity-related signaling pathways and pave the way for combating depression using combination therapy. Full article
(This article belongs to the Section Cells of the Nervous System)
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16 pages, 1247 KiB  
Article
Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space
by Mathilde Wullen, Valentine Bouet, Thomas Freret and Jean-Marie Billard
Cells 2025, 14(15), 1186; https://doi.org/10.3390/cells14151186 - 31 Jul 2025
Viewed by 356
Abstract
Background: We recently reported sex-dependent impairment in cognitive functions in male and female mice exposed for 24 h, 48 h or 15 days to 2G hypergravity (HG). Methods: In the present study, we investigated brain functional correlates by analyzing synaptic activity and plasticity [...] Read more.
Background: We recently reported sex-dependent impairment in cognitive functions in male and female mice exposed for 24 h, 48 h or 15 days to 2G hypergravity (HG). Methods: In the present study, we investigated brain functional correlates by analyzing synaptic activity and plasticity in the CA1 area of the hippocampus in both genders of mice previously exposed to 2G for the same duration. This was assessed by electrophysiological extracellular recordings in ex vivo slice preparations. Results: Basal synaptic transmission and glutamate release were unchanged regardless of HG duration. However, plasticity was altered in a sex- and time-specific manner. In males, long-term potentiation (LTP) induced by strong high-frequency stimulation and NMDA receptor (NMDAr) activation was reduced by 26% after 24 h of exposure but recovered at later timepoints. This deficit was reversed by D-serine or glycine, suggesting decreased activation at the NMDAr co-agonist site. In females, LTP deficits (23%) were found only after 15 days following mild theta burst stimulation and were not reversed by D-serine. Long-term depression (LTD) was unaffected in both sexes. Conclusions: This study highlights, for the first time, sex-dependent divergence in the CA1 hippocampal plasticity timeline following 2G exposure. The synaptic changes depend on exposure duration and the stimulation protocol and could underlie the previously observed cognitive deficits. Full article
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9 pages, 477 KiB  
Opinion
Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection
by Balázs Sonkodi
Cells 2025, 14(15), 1182; https://doi.org/10.3390/cells14151182 - 31 Jul 2025
Viewed by 190
Abstract
The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the [...] Read more.
The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Insights into the Pathophysiology of NeuroCOVID: Current Topics)
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16 pages, 3366 KiB  
Article
Numerical Analysis of Microfluidic Motors Actuated by Reconfigurable Induced-Charge Electro-Osmotic Whirling Flow
by Jishun Shi, Zhipeng Song, Xiaoming Chen, Ziang Bai, Jialin Yu, Qihang Ye, Zipeng Yang, Jianru Qiao, Shuhua Ma and Kailiang Zhang
Micromachines 2025, 16(8), 895; https://doi.org/10.3390/mi16080895 (registering DOI) - 31 Jul 2025
Viewed by 200
Abstract
The detection of proteins plays a key role in disease diagnosis and drug development. For this, we numerically investigated a novel microfluidic motor actuated by an induced-charge electro-osmotic (ICEO) whirling flow. An alternating current–flow field effect transistor is engineered to modulate the profiles [...] Read more.
The detection of proteins plays a key role in disease diagnosis and drug development. For this, we numerically investigated a novel microfluidic motor actuated by an induced-charge electro-osmotic (ICEO) whirling flow. An alternating current–flow field effect transistor is engineered to modulate the profiles of ICEO streaming to stimulate and adjust the whirling flow in the circle microfluidic chamber. Based on this, we studied the distribution of an ICEO whirling flow in the detection chamber by tuning the fixed potential on the gate electrodes by the simulations. Then, we established a fluid–structure interaction model to explore the influence of blade structure parameters on the rotation performance of microfluidic motors. In addition, we investigated the rotation dependence of microfluidic motors on the potential drop between two driving electrodes and fixed potential on the gate electrodes. Next, we numerically explored the capability of these microfluidic motors for the detection of low-abundance proteins. Finally, we studied the regulating effect of potential drops between the driving electrodes on the detection performance of microfluidic motors by numerical simulations. Microfluidic motors actuated by an ICEO whirling flow hold good potential in environmental monitoring and disease diagnosis for the outstanding advantages of flexible controllability, a simple structure, and gentle work condition. Full article
(This article belongs to the Special Issue Recent Development of Micro/Nanofluidic Devices, 2nd Edition)
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