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15 pages, 8949 KiB  
Article
Protein Expression of TXNIP in the Dopaminergic Neurons of Subjects with Parkinson’s Disease: Evidence from a Pilot Study
by Francesca A. Schillaci, Giuseppe Lanza, Maria Grazia Salluzzo, Raffaele Ferri and Michele Salemi
Life 2025, 15(8), 1252; https://doi.org/10.3390/life15081252 (registering DOI) - 7 Aug 2025
Abstract
Parkinson’s disease (PD) is a progressive, multisystemic α-synucleinopathy, recognized as the second most prevalent neurodegenerative disorder globally. Its neuropathology is characterized by the degeneration of dopaminergic neurons, particularly in the substantia nigra pars compacta (SNpc), and the intraneuronal accumulation of α-synuclein-forming Lewy bodies. [...] Read more.
Parkinson’s disease (PD) is a progressive, multisystemic α-synucleinopathy, recognized as the second most prevalent neurodegenerative disorder globally. Its neuropathology is characterized by the degeneration of dopaminergic neurons, particularly in the substantia nigra pars compacta (SNpc), and the intraneuronal accumulation of α-synuclein-forming Lewy bodies. Oxidative stress is a key contributor to PD pathogenesis. Thioredoxin-interacting protein (TXNIP) is a crucial regulator of cellular redox balance, inhibiting the antioxidant function of thioredoxin. This pilot study aimed to investigate the protein expression and localization of TXNIP in the SNpc of PD patients compared to healthy controls. We performed immunohistochemical analyses on 12 post-mortem human brain sections (formalin-fixed, paraffin-embedded) from six subjects with PD and six healthy controls. The study was performed on PD subjects with Braak stage 6. Our findings revealed that in control samples, TXNIP protein was distinctly and closely associated with neuromelanin (NM) pigment within the cytoplasm of SNpc dopaminergic neurons. Conversely, in PD samples, there was a markedly weak cytoplasmic expression of TXNIP, and critically, this association with NM pigment was absent. Furthermore, PD samples exhibited a significant reduction in both dopaminergic neurons and NM content, consistent with advanced disease. These findings, which mirror previous transcriptomic data showing TXNIP gene under-expression in the same subjects, suggest that altered TXNIP expression and localization in SNpc dopaminergic neurons are features of late-stage PD, potentially reflecting neuronal dysfunction and loss. Full article
(This article belongs to the Special Issue Regulation of Cellular Signaling Pathways in the Metabolic Syndrome)
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17 pages, 2763 KiB  
Article
Extended Reality-Based Proof-of-Concept for Clinical Assessment Balance and Postural Disorders for Personalized Innovative Protocol
by Fabiano Bini, Michela Franzò, Alessia Finti, Francesca Tiberi, Veronica Maria Teresa Grillo, Edoardo Covelli, Maurizio Barbara and Franco Marinozzi
Bioengineering 2025, 12(8), 850; https://doi.org/10.3390/bioengineering12080850 (registering DOI) - 7 Aug 2025
Abstract
Background: Clinical assessment of balance and postural disorders is usually carried out through several common practices including tests such as the Subjective Visual Vertical (SVV) and Limit of Stability (LOS). Nowadays, several cutting-edge technologies have been proposed as supporting tools for stability evaluation. [...] Read more.
Background: Clinical assessment of balance and postural disorders is usually carried out through several common practices including tests such as the Subjective Visual Vertical (SVV) and Limit of Stability (LOS). Nowadays, several cutting-edge technologies have been proposed as supporting tools for stability evaluation. Extended Reality (XR) emerges as a powerful instrument. This proof-of-concept study aims to assess the feasibility and potential clinical utility of a novel MR-based framework integrating HoloLens 2, Wii Balance Board, and Azure Kinect for multimodal balance assessment. An innovative test is also introduced, the Innovative Dynamic Balance Assessment (IDBA), alongside an MR version of the SVV test and the evaluation of their performance in a cohort of healthy individuals. Results: All participants reported SVV deviations within the clinically accepted ±2° range. The IDBA results revealed consistent sway and angular profiles across participants, with statistically significant differences in posture control between opposing target directions. System outputs were consistent, with integrated parameters offering a comprehensive representation of postural strategies. Conclusions: The MR-based framework successfully delivers integrated, multimodal measurements of postural control in healthy individuals. These findings support its potential use in future clinical applications for balance disorder assessment and personalized rehabilitation. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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19 pages, 12670 KiB  
Article
Risk Assessment of Flood Disasters with Multi-Source Data and Its Spatial Differentiation Characteristics
by Wenxia Jing, Yinghua Song, Wei Lv and Junyi Yang
Sustainability 2025, 17(15), 7149; https://doi.org/10.3390/su17157149 (registering DOI) - 7 Aug 2025
Abstract
The changing global climate and rapid urbanization make extreme rainstorm events frequent, and the flood disaster caused by rainstorm has become a prominent problem of urban public safety in China, which severely restricts the healthy and sustainable development of social economy. The weight [...] Read more.
The changing global climate and rapid urbanization make extreme rainstorm events frequent, and the flood disaster caused by rainstorm has become a prominent problem of urban public safety in China, which severely restricts the healthy and sustainable development of social economy. The weight calculation method of traditional risk assessment model is single and ignores the difference of multi-dimensional information space involved in risk analysis. This study constructs a flood risk assessment model by incorporating natural, social, and economic factors into an indicator system structured around four dimensions: hazard, exposure, vulnerability, and disaster prevention and mitigation capacity. A combination of the Analytic Hierarchy Process (AHP) and the entropy weight method is employed to optimize both subjective and objective weights. Taking the central urban area of Wuhan with a high flood risk as an example, based on the risk assessment values, spatial autocorrelation analysis, cluster analysis, outlier analysis, and hotspot analysis are applied to explore the spatial clustering characteristics of risks. The results show that the overall assessment level of flood hazard in central urban area of Wuhan is medium, the overall assessment level of exposure and vulnerability is low, and the overall disaster prevention and mitigation capability is medium. The overall flood risk levels in Wuchang and Jianghan are the highest, while some areas in Qingshan and Hanyang have the lowest levels. The spatial characteristics of each dimension evaluation index show obvious autocorrelation and spatial differentiation. These findings aim to provide valuable suggestions and references for reducing urban disaster risks and achieving sustainable urban development. Full article
(This article belongs to the Special Issue Sustainable Transport and Land Use for a Sustainable Future)
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15 pages, 1477 KiB  
Article
Objectification of the Functional Myodiagnosis Muscle Test
by Josef Franz Mahlknecht, Eugen Burtscher, Ivan Ramšak, Christine Zürcher and Johannes Bernard
J. Clin. Med. 2025, 14(15), 5555; https://doi.org/10.3390/jcm14155555 - 6 Aug 2025
Abstract
Objective: This study aimed to investigate whether the subjective assessments of strong and weak muscles in the Functional Myodiagnosis muscle test (FMD-MT) can be objectively and reproducibly verified using physically measurable parameters. Additionally, we sought to evaluate the reliability of the manual muscle [...] Read more.
Objective: This study aimed to investigate whether the subjective assessments of strong and weak muscles in the Functional Myodiagnosis muscle test (FMD-MT) can be objectively and reproducibly verified using physically measurable parameters. Additionally, we sought to evaluate the reliability of the manual muscle test in order to reinforce the scientific evidence supporting this accepted, yet not widely adopted, complementary medicine method. Methods: In a crossover observational study, three experienced medical practitioners conducted the FMD-MT of the rectus femoris muscle on 24 healthy participants using a specially designed therapy bench, with all measurements recorded via an oscillogram. The study investigated the force–time integral, joint angle change, additional force load, mean force turning point 1, as well as the interrater reliability and validity of both examiner assessments and instrumental analyses for the two muscle reaction variants: strong and weak. Results: A significant difference between the response pattern of strong and weak muscles was identified for the force–time integral (p = 0.005), the change in joint angle (p < 0.001), and the additional force load (p = 0.001). No difference between strong and weak muscles could be detected regarding the force turning point 1 (p = 0.972). The examiners demonstrated 100% accuracy in identifying weak muscle reactions as weak, and 99.2% accuracy in identifying strong muscle reactions as strong (p = 0.316). The overall intra-class correlation coefficient was 0.984. The oscillogram correctly visualized weak muscle reactions in weak muscles with an accuracy of 81.7%, and strong muscle reactions in strong muscles with an accuracy of 86.7% (p = 0.289). Conclusions: The Functional Myodiagnosis muscle test (FMD-MT) enables a clear and objective differentiation between strong and weak muscles, with statistically significant differences observed in the force–time integral, additional force load, and joint angle changes. Under rigorously standardized testing conditions, the FMD-MT of the rectus femoris muscle demonstrates a validity rate of 99.6% and an excellent reliability (ICC 0.984). Consequently, the FMD muscle test proves to be a reliable, reproducible, and objective diagnostic method. Trial registration: German Register of Clinical Studies U1111-1212-6622. Full article
(This article belongs to the Section Sports Medicine)
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25 pages, 4450 KiB  
Article
Analyzing Retinal Vessel Morphology in MS Using Interpretable AI on Deep Learning-Segmented IR-SLO Images
by Asieh Soltanipour, Roya Arian, Ali Aghababaei, Fereshteh Ashtari, Yukun Zhou, Pearse A. Keane and Raheleh Kafieh
Bioengineering 2025, 12(8), 847; https://doi.org/10.3390/bioengineering12080847 (registering DOI) - 6 Aug 2025
Abstract
Multiple sclerosis (MS), a chronic disease of the central nervous system, is known to cause structural and vascular changes in the retina. Although optical coherence tomography (OCT) and fundus photography can detect retinal thinning and circulatory abnormalities, these findings are not specific to [...] Read more.
Multiple sclerosis (MS), a chronic disease of the central nervous system, is known to cause structural and vascular changes in the retina. Although optical coherence tomography (OCT) and fundus photography can detect retinal thinning and circulatory abnormalities, these findings are not specific to MS. This study explores the potential of Infrared Scanning-Laser-Ophthalmoscopy (IR-SLO) imaging to uncover vascular morphological features that may serve as MS-specific biomarkers. Using an age-matched, subject-wise stratified k-fold cross-validation approach, a deep learning model originally designed for color fundus images was adapted to segment optic disc, optic cup, and retinal vessels in IR-SLO images, achieving Dice coefficients of 91%, 94.5%, and 97%, respectively. This process included tailored pre- and post-processing steps to optimize segmentation accuracy. Subsequently, clinically relevant features were extracted. Statistical analyses followed by SHapley Additive exPlanations (SHAP) identified vessel fractal dimension, vessel density in zones B and C (circular regions extending 0.5–1 and 0.5–2 optic disc diameters from the optic disc margin, respectively), along with vessel intensity and width, as key differentiators between MS patients and healthy controls. These findings suggest that IR-SLO can non-invasively detect retinal vascular biomarkers that may serve as additional or alternative diagnostic markers for MS diagnosis, complementing current invasive procedures. Full article
(This article belongs to the Special Issue AI in OCT (Optical Coherence Tomography) Image Analysis)
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10 pages, 250 KiB  
Article
Bullying Experiences Among Lithuanian Adolescents: The Associations Between Subjective Happiness and Well-Being
by Margarita Kubilevičiūtė Sakalauskienė, Rokas Šambaras and Sigita Lesinskienė
Psychiatry Int. 2025, 6(3), 97; https://doi.org/10.3390/psychiatryint6030097 (registering DOI) - 6 Aug 2025
Abstract
Background: Bullying is a significant problem worldwide and in Lithuania, especially among children and adolescents. This study aimed to assess the associations of bullying with adolescents’ subjective sense of happiness and general health. Methods: A cross-sectional study was conducted using an anonymous written [...] Read more.
Background: Bullying is a significant problem worldwide and in Lithuania, especially among children and adolescents. This study aimed to assess the associations of bullying with adolescents’ subjective sense of happiness and general health. Methods: A cross-sectional study was conducted using an anonymous written questionnaire. Adolescents at various schools across Lithuanian cities and districts were surveyed to investigate the frequency of bullying among them over the past six months and its impact on their subjective sense of happiness and well-being. Results: This study included 4124 students from seventh to tenth grade; their average age was 14.48 ± 1.15 years, with 49.35% being boys. Over the past six months, the highest bullying incidence occurred at school, accounting for 25.79% of the cases. Only half of the respondents (48.81%) felt happy, and a little more than half felt healthy (63.11%). It was found that bullying at school (ρs = −0.224; ρs = −0.197), outside school (ρs = −0.207; ρs = −0.180), and online (ρs = −0.175; ρs = −0.110) is associated with adolescents’ sense of happiness and health. Conclusion: Bullying is common among Lithuanian adolescents and has a negative impact on their subjective happiness and well-being. It is crucial to develop prevention initiatives to decrease bullying in schools and within the community. Full article
19 pages, 1856 KiB  
Article
Combination Therapy with Trehalose and Hyaluronic Acid Restores Tear Lipid Layer Functionality by Ameliorating Inflammatory Response Protein Markers on the Ocular Surface of Dry Eye Patients
by Natarajan Perumal, Caroline Manicam, Eunjin Jeong, Sarah Runde, Norbert Pfeiffer and Franz H. Grus
J. Clin. Med. 2025, 14(15), 5525; https://doi.org/10.3390/jcm14155525 - 5 Aug 2025
Abstract
Objectives: Topical lubricants are the fundamental treatment for dry eye disease (DED). However, the molecular mechanisms underlying their efficacy remain unknown. Here, the protective effects of Thealoz® Duo with 3% trehalose and 0.15% hyaluronic acid are investigated in DED patients by a [...] Read more.
Objectives: Topical lubricants are the fundamental treatment for dry eye disease (DED). However, the molecular mechanisms underlying their efficacy remain unknown. Here, the protective effects of Thealoz® Duo with 3% trehalose and 0.15% hyaluronic acid are investigated in DED patients by a longitudinal clinical study and subsequent elucidation of the tear proteome and cell signaling changes. Methods: Participants were classified as moderate to severe DED (DRY, n = 35) and healthy (CTRL, n = 23) groups. Specific DED subgroups comprising evaporative (DRYlip) and aqueous-deficient with DRYlip (DRYaqlip) were also classified. Only DED patients received Thealoz® Duo. All participants were clinically examined before (day 0, T1) and after the application of Thealoz® Duo at day 28 (T2) and day 56 (T3). Next, 174 individual tear samples from all groups at three time-points were subjected to proteomics analysis. Results: Clinically, Thealoz® Duo significantly improved the ocular surface disease index at T2 vs. T1 (DRY, p = 1.4 × 10−2; DRYlip, p = 9.2 × 10−3) and T3 vs. T1 (DRY, p = 2.1 × 10−5; DRYlip, p = 1.2 × 10−4), and the tear break-up time at T3 vs. T1 (DRY, p = 3.8 × 10−2; DRYlip, p = 1.4 × 10−2). Thealoz® Duo significantly ameliorated expression of inflammatory response proteins (p < 0.05) at T3, which was observed at T1 (DRY, p = 3.4 × 10−4; DRYlip, p = 7.1 × 10−3; DRYaqlip, p = 2.7 × 10−8). Protein S100-A8 (S100A8), Alpha-1-antitrypsin (SERPINA1), Annexin A1 (ANXA1), and Apolipoprotein A-I (APOA1) were found to be significantly reduced in all the DED subgroups. The application of Thealoz® Duo showed the therapeutic characteristic of the anti-inflammatory mechanism by promoting the expression of (Metalloproteinase inhibitor 1) TIMP1 in all the DED subgroups. Conclusions: Thealoz® Duo substantially improved the DED symptoms and restored the functionality of the tear lipid layer to near normal in DRYlip and DRY patients by ameliorating inflammation. Notably, this study unravels the novel mechanistic alterations underpinning the healing effects of Thealoz® Duo in DED subgroups in a time-dependent manner, which supports the improvement in corresponding clinical attributes. Full article
(This article belongs to the Section Ophthalmology)
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16 pages, 4455 KiB  
Article
Effect of Alpha2-Plasmin Inhibitor C-Terminal Heterogeneity on Clot Lysis and Clot Structure
by Réka Bogáti, Barbara Baráth, Dóra Pituk, Rita Orbán-Kálmándi, Péter Szűcs, Zoltán Hegyi, Zsuzsanna Bereczky, Zsuzsa Bagoly and Éva Katona
Biomolecules 2025, 15(8), 1127; https://doi.org/10.3390/biom15081127 - 5 Aug 2025
Viewed by 54
Abstract
Alpha2-plasmin inhibitor (α2PI) has a heterogeneous structure due to proteolytic cleavages in the circulation. The C-terminally cleaved form loses the plasminogen binding site and is, therefore, a slow plasmin inhibitor (NPB-α2PI). As FXIII primarily crosslinks the plasminogen-binding intact form (PB-α2PI) to fibrin, the [...] Read more.
Alpha2-plasmin inhibitor (α2PI) has a heterogeneous structure due to proteolytic cleavages in the circulation. The C-terminally cleaved form loses the plasminogen binding site and is, therefore, a slow plasmin inhibitor (NPB-α2PI). As FXIII primarily crosslinks the plasminogen-binding intact form (PB-α2PI) to fibrin, the effect of NPB-α2PI on fibrinolysis has been less studied. Herein, we investigated the effect of C-terminal truncation. Total-, PB-, and NPB-α2PI antigen levels and α2PI incorporation were measured by ELISAs from samples of 80 healthy individuals. Clot lysis parameters of the same subjects were investigated using an in vitro clot lysis assay. α2PI incorporation into the clot was demonstrated by Western blotting. Clot lysis and clot structure were also analyzed using an α2PI-deficient plasma substituted with recombinant PB- and NPB-α2PI. Both plasma and clot-bound levels of total- and NPB-α2PI showed a significant positive correlation with clot lysis parameters. NPB-α2PI was detected in the clot due to non-covalent binding. Regardless of the type of binding, both forms affected the clot structure by increasing the thickness of the fibrin fibers and reducing the pore size. In conclusion, we found that NPB-α2PI can bind non-covalently to fibrin, and this binding contributes to changes in clot structure and inhibition of fibrinolysis. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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15 pages, 958 KiB  
Article
Can Plantar Pressure Distribution During Gait Be Estimated from Quiet Stance in Healthy Individuals?
by Marta Mirando, Chiara Pavese, Valeria Pingue, Stefania Sozzi and Antonio Nardone
J. Funct. Morphol. Kinesiol. 2025, 10(3), 301; https://doi.org/10.3390/jfmk10030301 - 5 Aug 2025
Viewed by 89
Abstract
Objectives: We assessed the difference between quiet stance and gait in the spatial distribution and intensity of foot plantar pressures and whether it is possible to estimate the distribution during gait from data obtained during stance. Methods: A total of 60 [...] Read more.
Objectives: We assessed the difference between quiet stance and gait in the spatial distribution and intensity of foot plantar pressures and whether it is possible to estimate the distribution during gait from data obtained during stance. Methods: A total of 60 healthy subjects with a mean age of 31.0 ± 9.4 years performed two trials for quiet stance and four trials for gait on a baropodometric walkway with their eyes open. Foot plantar pressures were recorded from 10 areas of the foot sole. Results: During quiet stance, the highest plantar pressure occurred at metatarsal heads (M2 to M4) and the medial (MH) and lateral halves of the heel (LH). During gait, the profile of plantar pressure values was like that during stance, but significantly higher. The differences concentrated at the big toe (T1), M2 to M4, MH, and LH, whilst toes (T2,3,4,5) and midfoot (MF) showed the smallest difference. A significant positive correlation was found between the corresponding areas of foot pressure during gait and stance. Conclusions: During quiet stance and gait, the overall profile of plantar pressure distribution was similar. During quiet stance, the subjects loaded more on the heels, in keeping with the known position of the center of pressure just in front of the ankles. During gait, higher pressures on the metatarsal areas are related to the forward propulsion of the center of mass. The correlation between the corresponding areas of foot pressure during gait and stance suggests that the pressure distribution during gait can partly be estimated from that during stance. This finding might be useful in most clinical settings when a single sensorized platform rather than a complete walkway is available. Full article
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19 pages, 3739 KiB  
Article
Disturbances in Resting State Functional Connectivity in Schizophrenia: A Study of Hippocampal Subregions, the Parahippocampal Gyrus and Functional Brain Networks
by Raghad M. Makhdoum and Adnan A. S. Alahmadi
Diagnostics 2025, 15(15), 1955; https://doi.org/10.3390/diagnostics15151955 - 4 Aug 2025
Viewed by 154
Abstract
Background/Objectives: Schizophrenia exhibits symptoms linked to the hippocampus and parahippocampal gyrus. This includes the entorhinal cortex (ERC) and perirhinal cortex (PRC) as anterior parts, along with the posterior segment known as the parahippocampal cortex (PHC). However, recent research has detailed atlases based on [...] Read more.
Background/Objectives: Schizophrenia exhibits symptoms linked to the hippocampus and parahippocampal gyrus. This includes the entorhinal cortex (ERC) and perirhinal cortex (PRC) as anterior parts, along with the posterior segment known as the parahippocampal cortex (PHC). However, recent research has detailed atlases based on cytoarchitectural characteristics and the hippocampus divided into four subregions: cornu ammonis (CA), dentate gyrus (DG), subiculum (SUB), and hippocampal–amygdaloid transition (HATA). This study aimed to explore the functional connectivity (FC) changes between these hippocampal subregions and the parahippocampal gyrus structures (ERC, PRC, and PHC) as well as between hippocampal subregions and various functional brain networks in schizophrenia. Methods: In total, 50 individuals with schizophrenia and 50 matched healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI). Results: The results showed alterations characterized by increases and decreases in the strength of the positive connectivity between the parahippocampal gyrus structures and the four hippocampal subregions when comparing patients with schizophrenia with healthy subjects. Alterations were observed among the hippocampal subregions and functional brain networks, as well as the formation of new connections and absence of connections. Conclusions: There is strong evidence that the different subregions of the hippocampus have unique functions and their connectivity with the parahippocampal cortices and brain networks are affected by schizophrenia. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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27 pages, 2005 KiB  
Article
Glyoxalase 1 Inducer, trans-Resveratrol and Hesperetin–Dietary Supplement with Multi-Modal Health Benefits
by Mingzhan Xue, Naila Rabbani and Paul J. Thornalley
Antioxidants 2025, 14(8), 956; https://doi.org/10.3390/antiox14080956 (registering DOI) - 4 Aug 2025
Viewed by 208
Abstract
A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose [...] Read more.
A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article
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40 pages, 1970 KiB  
Review
Periodontal Microbial Profiles Across Periodontal Conditions in Pediatric Subjects: A Narrative Review
by Federica Di Spirito, Maria Pia Di Palo, Giuseppina De Benedetto, Federica Piedepalumbo, Marzio Galdi, Davide Cannatà, Noemi Cafà and Maria Contaldo
Microorganisms 2025, 13(8), 1813; https://doi.org/10.3390/microorganisms13081813 - 3 Aug 2025
Viewed by 152
Abstract
Periodontal diseases in pediatric subjects represent a challenging and relatively underexplored area compared to the extensive data available about periodontal diseases in adults. The present narrative review aims to explore the periodontal status and the related subgingival and/or salivary microbial profiles in pediatric [...] Read more.
Periodontal diseases in pediatric subjects represent a challenging and relatively underexplored area compared to the extensive data available about periodontal diseases in adults. The present narrative review aims to explore the periodontal status and the related subgingival and/or salivary microbial profiles in pediatric subjects (≤18 years), focusing also on the state of health or systemic diseases. In healthy periodontium, early colonizers, such as Streptococcus and Actinomyces spp., dominate the subgingival microbiota, supporting an eubiosis state. Low levels of Candida albicans and latent Herpesviridae may be detected. In gingivitis, the microbial profile shifts towards more pathogenic species, including Prevotella intermedia and Fusobacterium nucleatum. In necrotizing gingivitis, typically affecting systemically compromised children, the microbial profile is characterized by spirochetes, Fusobacterium, and Prevotella intermedia. Viral coinfections—especially with HSV, CMV, and EBV—are more frequently detected. In periodontitis, the microbiota was dominated by red complex pathogens along with Aggregatibacter actinomycetemcomitans in the aggressive forms, especially in systemically compromised children, as Herpesviridae reactivation and co-infections. Fungal involvement is less well characterized; Candida albicans may be present, particularly in cases of severe immune suppression. Nevertheless, the lack of pediatric longitudinal studies investigating periodontal disease progression after periodontal treatment and related changes in microbiological composition limited the understanding and exploration of the oral microbiota over time. Full article
(This article belongs to the Section Medical Microbiology)
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16 pages, 1795 KiB  
Article
Assessing and Improving the Reproducibility of Cerebrovascular Reactivity Evaluations in Healthy Subjects Using Short-Breath-Hold fMRI
by Emely Renger, Till-Karsten Hauser, Uwe Klose, Ulrike Ernemann and Leonie Zerweck
Diagnostics 2025, 15(15), 1946; https://doi.org/10.3390/diagnostics15151946 - 3 Aug 2025
Viewed by 252
Abstract
Background/Objectives: Cerebrovascular reactivity (CVR) is a key marker of cerebrovascular function, facilitating the early detection of neurovascular dysfunction. Breath-hold functional MRI (bh-fMRI) is a non-invasive method for assessing CVR. This study evaluates the reproducibility of bh-fMRI using short breath-hold periods, which are [...] Read more.
Background/Objectives: Cerebrovascular reactivity (CVR) is a key marker of cerebrovascular function, facilitating the early detection of neurovascular dysfunction. Breath-hold functional MRI (bh-fMRI) is a non-invasive method for assessing CVR. This study evaluates the reproducibility of bh-fMRI using short breath-hold periods, which are practical for clinical use. Methods: In a prospective study, 50 healthy subjects underwent three self-paced, end-expiration bh-fMRI sessions with 9 s breath-hold periods at 3T. A 30 min break between the second and third sessions was included. The reproducibility of the percentage signal change (PSC) in predefined volumes of interest for a ±0 s, ±3 s and ±6 s interval around the cerebellar peak (IAP)) was evaluated. The intraclass correlation coefficient (ICC) and the intra-personal coefficient of variation (CVintra) were calculated between the individual sessions. Results: This study demonstrated excellent reproducibility, with an ICC (2, k) for a ±0 s IAP across all sessions at 0.887 (95% CI: 0.882–0.892). The ICC values remained within an excellent range even when the participants left the scanner between sessions. The CVintra for the ±0 s IAP (14.54% ± 8.54%) remained below the 33% fiducial limit. A larger IAP revealed higher ICC values but higher CVintra values and lower PSC values. Conclusions: Bh-fMRI with 9 s breath-hold periods yields highly reproducible CVR assessments, supporting its feasibility for clinical implementation. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Neurological Diseases)
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18 pages, 3360 KiB  
Article
Hydrogen Sulfide Has a Minor Impact on Human Gut Microbiota Across Age Groups
by Linshu Liu, Johanna M. S. Lemons, Jenni Firrman, Karley K. Mahalak, Venkateswari J. Chetty, Adrienne B. Narrowe, Stephanie Higgins, Ahmed M. Moustafa, Aurélien Baudot, Stef Deyaert and Pieter Van den Abbeele
Sci 2025, 7(3), 102; https://doi.org/10.3390/sci7030102 - 1 Aug 2025
Viewed by 128
Abstract
Hydrogen sulfide (H2S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H2S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health [...] Read more.
Hydrogen sulfide (H2S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H2S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health conditions, it may also contribute to inflammatory responses and gut barrier dysfunction. Controlling H2S production in the GIT is important for maintaining a healthy gut microbiome. However, research on this subject is limited due to the gaseous nature of the chemical and the difficulty of accessing the GIT in situ. In the present ex vivo experiment, we used a single-dose sodium sulfide preparation (SSP) as a H2S precursor to test the effect of H2S on the human gut microbiome across different age groups, including breastfed infants, toddlers, adults, and older adults. Metagenomic sequencing and metabolite measurements revealed that the development of the gut microbial community and the production of short-chain fatty-acids (SCFAs) were age-dependent; that the infant and the older adult groups were more sensitive to SSP exposure; that exogeneous SSP suppressed SCFA production across all age groups, except for butyrate in the older adult group, suggesting that H2S selectively favors specific gut microbial processes. Full article
(This article belongs to the Section Biology Research and Life Sciences)
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Article
Investigating the Diagnostic Utility of LncRNA GAS5 in NAFLD Patients
by Maysa A. Mobasher, Alaa Muqbil Alsirhani, Sahar Abdulrahman Alkhodair, Amir Abd-elhameed, Shereen A. Baioumy, Marwa M. Esawy and Marwa A. Shabana
Biomedicines 2025, 13(8), 1873; https://doi.org/10.3390/biomedicines13081873 - 1 Aug 2025
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Abstract
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in [...] Read more.
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in patients with NAFLD and find out if they are related to any clinical factors. Subjects and Methods: Thirty-eight age-matched healthy persons and thirty-eight NAFLD patients were enrolled. Patients were split into the following three groups: non-alcoholic steatohepatitis (NASH) (n = 12), patients with NAFLD-related cirrhosis (n = 8), and patients with NAFLD-related simple steatosis (n = 18). Real-time PCR was utilized to examine the expression. Results: The lncRNA GAS5 and NOTCH2 were higher in NAFLD cases in comparison to controls. On the other hand, microRNA-29a-3p was underexpressed in NAFLD cases in comparison to controls. Regarding NAFLD diagnosis, lncRNA GAS5 was the best single marker with a sensitivity of 100% and a specificity of 94.7% at the cutoff values of ≥1.16-fold change. Regarding different stages of the disease, the highest level of lncRNA GAS5 was in cirrhosis. lncRNA GAS5 expression, among other studied parameters, is still a significant predictor of NAFLD (adjusted odds ratio of 162, C.I. = 5.7–4629) (p = 0.003). LncRNA GAS5 has a positive correlation with NOTCH2 and a negative correlation with miR-29a-3p. LncRNA GAS5, NOTCH2, and RNA-29a-3p were significantly different in NAFLD cases compared to controls. Conclusions: lncRNA GAS5 appears to be the most effective single marker for detecting NAFLD. LncRNA GAS5 expression is a significant independent predictor of NAFLD. LncRNA GAS5 can differentiate different NAFLD stages. Full article
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