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Search Results (1,529)

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38 pages, 471 KiB  
Review
Sleep Disorders and Stroke: Pathophysiological Links, Clinical Implications, and Management Strategies
by Jamir Pitton Rissardo, Ibrahim Khalil, Mohamad Taha, Justin Chen, Reem Sayad and Ana Letícia Fornari Caprara
Med. Sci. 2025, 13(3), 113; https://doi.org/10.3390/medsci13030113 - 5 Aug 2025
Abstract
Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, [...] Read more.
Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article
27 pages, 11710 KiB  
Article
Assessing ResNeXt and RegNet Models for Diabetic Retinopathy Classification: A Comprehensive Comparative Study
by Samara Acosta-Jiménez, Valeria Maeda-Gutiérrez, Carlos E. Galván-Tejada, Miguel M. Mendoza-Mendoza, Luis C. Reveles-Gómez, José M. Celaya-Padilla, Jorge I. Galván-Tejada and Antonio García-Domínguez
Diagnostics 2025, 15(15), 1966; https://doi.org/10.3390/diagnostics15151966 - 5 Aug 2025
Abstract
Background/Objectives: Diabetic retinopathy is a leading cause of vision impairment worldwide, and the development of reliable automated classification systems is crucial for early diagnosis and clinical decision-making. This study presents a comprehensive comparative evaluation of two state-of-the-art deep learning families for the task [...] Read more.
Background/Objectives: Diabetic retinopathy is a leading cause of vision impairment worldwide, and the development of reliable automated classification systems is crucial for early diagnosis and clinical decision-making. This study presents a comprehensive comparative evaluation of two state-of-the-art deep learning families for the task of classifying diabetic retinopathy using retinal fundus images. Methods: The models were trained and tested in both binary and multi-class settings. The experimental design involved partitioning the data into training (70%), validation (20%), and testing (10%) sets. Model performance was assessed using standard metrics, including precision, sensitivity, specificity, F1-score, and the area under the receiver operating characteristic curve. Results: In binary classification, the ResNeXt101-64x4d model and RegNetY32GT model demonstrated outstanding performance, each achieving high sensitivity and precision. For multi-class classification, ResNeXt101-32x8d exhibited strong performance in early stages, while RegNetY16GT showed better balance across all stages, particularly in advanced diabetic retinopathy cases. To enhance transparency, SHapley Additive exPlanations were employed to visualize the pixel-level contributions for each model’s predictions. Conclusions: The findings suggest that while ResNeXt models are effective in detecting early signs, RegNet models offer more consistent performance in distinguishing between multiple stages of diabetic retinopathy severity. This dual approach combining quantitative evaluation and model interpretability supports the development of more robust and clinically trustworthy decision support systems for diabetic retinopathy screening. Full article
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16 pages, 390 KiB  
Review
The Role of Quantitative EEG in the Diagnosis of Alzheimer’s Disease
by Vasileios Papaliagkas
Diagnostics 2025, 15(15), 1965; https://doi.org/10.3390/diagnostics15151965 - 5 Aug 2025
Abstract
Alzheimer’s disease is the most prevalent neurodegenerative disorder leading to progressive cognitive decline and functional impairment. Although advanced neuroimaging and cerebrospinal fluid biomarkers have improved early detection, their high costs, invasiveness, and limited accessibility restrict universal screening. Quantitative electroencephalography (qEEG) offers a non-invasive [...] Read more.
Alzheimer’s disease is the most prevalent neurodegenerative disorder leading to progressive cognitive decline and functional impairment. Although advanced neuroimaging and cerebrospinal fluid biomarkers have improved early detection, their high costs, invasiveness, and limited accessibility restrict universal screening. Quantitative electroencephalography (qEEG) offers a non-invasive and cost-effective alternative for assessing neurophysiological changes associated with AD. This review critically evaluates current evidence on EEG biomarkers, including spectral, connectivity, and complexity measures, discussing their pathophysiological basis, diagnostic accuracy, and clinical utility in AD. Limitations and future perspectives, especially in developing standardized protocols and integrating machine learning techniques, are also addressed. Full article
(This article belongs to the Special Issue EEG Analysis in Diagnostics)
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14 pages, 497 KiB  
Article
Sensitivity and Specificity of a Revised Version of the TRACK-MS Screening Battery for Early Detection of Cognitive Impairment in Patients with Multiple Sclerosis
by Luisa T. Balz, Ingo Uttner, Daniela Taranu, Deborah K. Erhart, Tanja Fangerau, Stefanie Jung, Herbert Schreiber, Makbule Senel, Ioannis Vardakas, Dorothée E. Lulé and Hayrettin Tumani
Biomedicines 2025, 13(8), 1902; https://doi.org/10.3390/biomedicines13081902 - 4 Aug 2025
Abstract
Background/Objectives: Cognitive impairment is one of the most common and debilitating clinical features of Multiple Sclerosis (MS). Neuropsychological assessment, however, is time-consuming and requires personal resources, so, due to limited resources in daily clinical practice, information on cognitive profiles is often lacking, [...] Read more.
Background/Objectives: Cognitive impairment is one of the most common and debilitating clinical features of Multiple Sclerosis (MS). Neuropsychological assessment, however, is time-consuming and requires personal resources, so, due to limited resources in daily clinical practice, information on cognitive profiles is often lacking, despite its high prognostic relevance. Time-saving and effective tools are required to bridge this gap. This study evaluates the sensitivity and specificity of a revised version of TRACK-MS (TRACK-MS-R), a recently published screening tool to identify cognitive impairment in MS in a fast and reliable way, offering a balance between efficiency and diagnostic yield for the individual patient. Methods: In this prospective cross-sectional study, 102 MS patients and 94 age-, sex-, and education-matched healthy controls (HC) completed an extensive neuropsychological assessment, including TRACK-MS-R, to test for cognitive processing speed (Symbol Digit Modalities Test, SDMT) and verbal fluency (Regensburger Word Fluency Test, RWT). Sensitivity of TRACK-MS-R was assessed by using the BICAMS-M battery as a reference, and specificity was determined by comparing MS patients to HC. Results: TRACK-MS-R demonstrated high sensitivity (97.44%) when compared to the gold standard as represented by BICAMS-M for early and accurately detecting cognitive impairment in MS patients. Additionally, as a potential cognitive marker, TRACK-MS-R showed a specificity of 82.98% in distinguishing MS patients from healthy controls. Conclusions: TRACK-MS-R proves to be a highly sensitive and time-efficient screening tool for detecting cognitive impairment in patients with MS, while demonstrating good specificity compared to HC. Whereas high sensitivity is a prerequisite for a valid screening tool, its relatively modest specificity compared to BICAMS-M (62.9%) calls for caution in interpreting standalone results but instead indicates more extensive neuropsychological testing. Its briefness and diagnostic accuracy support its implementation in routine clinical practice, particularly in time-constrained settings. Full article
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18 pages, 1351 KiB  
Review
Functional and Neuroplastic Effects of Cross-Education in Anterior Cruciate Ligament Rehabilitation: A Scoping Review with Bibliometric Analysis
by Jorge M. Vélez-Gutiérrez, Andrés Rojas-Jaramillo, Juan D. Ascuntar-Viteri, Juan D. Quintero, Francisco García-Muro San José, Bruno Bazuelo-Ruiz, Roberto Cannataro and Diego A. Bonilla
Appl. Sci. 2025, 15(15), 8641; https://doi.org/10.3390/app15158641 (registering DOI) - 4 Aug 2025
Abstract
Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional [...] Read more.
Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional and neuroplastic effects of CE rehabilitation post-ACLR. Following PRISMA-ScR and JBI guidelines, PubMed, Scopus, Web of Science, and PEDro were searched up to February 2025. A bibliometric analysis was also conducted to report keyword co-occurrence and identify trends in this line of research. Of 333 screened references, 14 studies (price index: 43% and low-to-moderate risk of bias) involving 721 participants (aged 17–45 years) met inclusion criteria. CE protocols (6–12 weeks; 2–5 sessions/week) incorporating isometric, concentric, and eccentric exercises demonstrated strength gains (10–31%) and strength preservation, alongside improved limb symmetry (5–14%) and dynamic balance (7–18%). There is growing interest in neuroplasticity and corticospinal excitability, although neuroplastic changes were assessed heterogeneously across studies. Findings support CE as a feasible and low-cost strategy to complement early-stage ACLR rehabilitation, especially when direct loading of the affected limb is limited. Standardized protocols for clinical intervention and neurophysiological assessment are needed. Full article
(This article belongs to the Special Issue Novel Approaches of Physical Therapy-Based Rehabilitation)
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11 pages, 1507 KiB  
Article
Peony Root Extract Controls AGE–RAGE Interaction, Suppresses AGE Formation, and Reduces Skin Dullness
by Kyoko Kanai, Kazal Boron Biswas, Asuka Hirasawa, Misaki Futamura, Kiyotaka Tanaka and Kotaro Sakamoto
Cosmetics 2025, 12(4), 163; https://doi.org/10.3390/cosmetics12040163 - 4 Aug 2025
Abstract
Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and [...] Read more.
Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and their receptor (receptor for AGEs [RAGE]) as contributing factors to skin dullness. AGEs themselves have a yellowish hue, contributing to “yellow dullness.” Additionally, AGE–RAGE signaling promotes melanin production in melanocytes and impairs keratinocyte differentiation as a result of inflammation. Therefore, regulating the AGE–RAGE interaction may help reduce skin dullness. Through screening various natural ingredients, we found that peony root extract (PRE) inhibits AGE formation and blocks AGE–RAGE binding. Furthermore, the presence of PRE leads to the suppression of AGE-induced melanin production in melanocytes and the restoration of impaired keratinocyte differentiation in glycated basement membrane components. In a human clinical study, topical application of a 1% PRE-containing lotion for 2 weeks significantly reduced melanin content, with a trend toward decreased AGE accumulation and visible spots on the cheeks. These findings support the potential of PRE as a multifunctional cosmetic ingredient that comprehensively addresses skin dullness by modulating the AGE–RAGE interaction. Full article
(This article belongs to the Special Issue Skin Anti-Aging Strategies)
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16 pages, 2864 KiB  
Article
RANKL/OPG Axis and Bone Mineral Density in Pediatric Inflammatory Bowel Disease
by Mariusz Olczyk, Agnieszka Frankowska, Marcin Tkaczyk, Anna Socha-Banasiak, Renata Stawerska, Anna Łupińska, Zuzanna Gaj, Ewa Głowacka and Elżbieta Czkwianianc
J. Clin. Med. 2025, 14(15), 5440; https://doi.org/10.3390/jcm14155440 - 1 Aug 2025
Viewed by 138
Abstract
Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population [...] Read more.
Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article
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39 pages, 1418 KiB  
Review
Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review
by Sama Thiab, Juberiya M. Azeez, Alekya Anala, Moksha Nanda, Somieya Khan, Alexandra E. Butler and Manjula Nandakumar
Cells 2025, 14(15), 1188; https://doi.org/10.3390/cells14151188 - 1 Aug 2025
Viewed by 100
Abstract
Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired [...] Read more.
Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article
(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)
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24 pages, 1154 KiB  
Article
Psychic and Cognitive Impacts of Cardiovascular Disease: Evidence from an Observational Study and Comparison by a Systematic Literature Review
by Irene Cappadona, Anna Anselmo, Davide Cardile, Giuseppe Micali, Fabio Mauro Giambò, Francesco Speciale, Daniela Costanzo, Piercataldo D'Aleo, Antonio Duca, Alessia Bramanti, Marina Garofano, Placido Bramanti, Francesco Corallo and Maria Pagano
Med. Sci. 2025, 13(3), 105; https://doi.org/10.3390/medsci13030105 - 1 Aug 2025
Viewed by 171
Abstract
Background/Objectives: Cardiovascular diseases (CVDs) are frequently associated with psychiatric and cognitive comorbidities. These conditions have been shown to significantly impact quality of life and clinical outcomes. This study aims to evaluate the prevalence of anxiety, depression, and cognitive deficits in patients with [...] Read more.
Background/Objectives: Cardiovascular diseases (CVDs) are frequently associated with psychiatric and cognitive comorbidities. These conditions have been shown to significantly impact quality of life and clinical outcomes. This study aims to evaluate the prevalence of anxiety, depression, and cognitive deficits in patients with CVD and to compare the results with existing evidence in the literature. Methods: A total of 74 patients were assessed using the following standardized screening tools: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI). A systematic review was then conducted to compare the findings with those reported in the literature. Results: Most previous studies using the MoCA reported an over 70% absence of cognitive impairment, whereas this study shows a balanced distribution between the absence of (32.4%) and mild (35%) or moderate (32%) impairment. Studies with the MMSE indicated high rates of absence of cognitive deficits (74–79%), but here, the rate of absence was lower (58%), with an increase in mild impairment (42%). Regarding depression, compared with studies showing only absence or moderate/severe forms, this study reveals a more balanced profile, with 57% without depression and with varying severity levels (22% mild, 19% moderate, and 3% severe). Finally, for anxiety, unlike previous asymmetric distributions, greater variability was observed, with 58% without anxiety and significant percentages of mild (26%), moderate (12%), and severe (4%) anxiety. Conclusions: The results highlight a significant and varied prevalence of anxiety, depression, and cognitive deficits, emphasizing the importance of a multidimensional assessment to improve clinical management and therapeutic outcomes. Full article
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12 pages, 954 KiB  
Article
Health-Related Quality of Life and Internalising Symptoms in Romanian Children with Congenital Cardiac Malformations: A Single-Centre Cross-Sectional Analysis
by Andrada Ioana Dumitru, Andreea Mihaela Kis, Mihail-Alexandru Badea, Adrian Lacatusu and Marioara Boia
Healthcare 2025, 13(15), 1882; https://doi.org/10.3390/healthcare13151882 - 1 Aug 2025
Viewed by 154
Abstract
Background and Objectives: Although survival after congenital cardiac malformations (CCM) has improved, little is known about Romanian children’s own perceptions of health-related quality of life (HRQoL) or their emotional burden. We compared HRQoL, depressive symptoms, and anxiety across lesion severity strata and [...] Read more.
Background and Objectives: Although survival after congenital cardiac malformations (CCM) has improved, little is known about Romanian children’s own perceptions of health-related quality of life (HRQoL) or their emotional burden. We compared HRQoL, depressive symptoms, and anxiety across lesion severity strata and explored clinical predictors of impaired HRQoL. Methods: In this cross-sectional study (1 May 2023–30 April 2025), 72 children (mean age 7.9 ± 3.0 years, 52.8% male) attending a tertiary cardiology clinic completed the Romanian-validated Pediatric Quality of Life Inventory (PedsQL), Children’s Depression Inventory (CDI) and the Screen for Child Anxiety-Related Emotional Disorders questionnaire (SCARED-C, child version). Lesions were classified as mild (n = 22), moderate (n = 34), or severe (n = 16). Left-ventricular ejection fraction (LVEF) and unplanned cardiac hospitalisations over the preceding 12 months were extracted from electronic records. Results: Mean PedsQL total scores declined stepwise by severity (mild 80.9 ± 7.3; moderate 71.2 ± 8.4; severe 63.1 ± 5.4; p < 0.001). CDI and SCARED-C scores rose correspondingly (CDI: 9.5 ± 3.0, 13.6 ± 4.0, 18.0 ± 2.7; anxiety: 15.2 ± 3.3, 17.2 ± 3.8, 24.0 ± 3.4; both p < 0.001). PedsQL correlated positively with LVEF (r = 0.51, p < 0.001) and negatively with hospitalisations (r = −0.39, p = 0.001), depression (r = −0.44, p < 0.001), and anxiety (r = −0.47, p < 0.001). In multivariable analysis, anatomical severity remained the sole independent predictor of lower HRQoL (β = −8.4 points per severity tier, p < 0.001; model R2 = 0.45). Children with ≥ 1 hospitalisation (n = 42) reported poorer HRQoL (69.6 ± 8.0 vs. 76.1 ± 11.1; p = 0.005) and higher depressive scores (p < 0.001). Conclusions: HRQoL and internalising symptoms in Romanian children with CCM worsen with increasing anatomical complexity and recent hospital utilisation. The severity tier outweighed functional markers as the main determinant of HRQoL, suggesting that psychosocial screening and support should be scaled to lesion complexity. Integrating the routine use of the Romanian-validated PedsQL, CDI, and SCARED-C questionnaire into cardiology follow-up may help identify vulnerable patients early and guide targeted interventions. Full article
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12 pages, 736 KiB  
Article
Visual Search Test for Residents Chronically Exposed to Methylmercury in the Minamata Area
by Shigeru Takaoka and Kenta Matsunaga
Toxics 2025, 13(8), 657; https://doi.org/10.3390/toxics13080657 - 31 Jul 2025
Viewed by 246
Abstract
In individuals exposed to relatively mild methylmercury, even if they appeared to be independent in activities of daily living (ADL), slower judgment and motor responses in daily activities were observed, suggesting potential cognitive impairment. To quantitatively assess this impairment, we measured reaction time [...] Read more.
In individuals exposed to relatively mild methylmercury, even if they appeared to be independent in activities of daily living (ADL), slower judgment and motor responses in daily activities were observed, suggesting potential cognitive impairment. To quantitatively assess this impairment, we measured reaction time (RT) in a visual search test, as a visual cognitive ability test. The study participants included 24 residents from contaminated areas with sensory impairments in the limbs but no visual field defects (E group), as well as 12 individuals from non-contaminated areas (Group C). The 24 participants from contaminated areas were further divided into two groups: 12 without hand motor coordination disorders (Group E-HA) and 12 with such disorders (Group E+HA). Participants were instructed to search for the target letter “Z” on a computer screen, and the visual stimuli consisted of two, six, or ten alphabet letters. An equal number of trials contained “Z” and did not contain “Z,” for a total of thirty trials, which were conducted twice. RT was significantly longer in Group E+HA, followed by Group E-HA, and then Group C. However, in the second test, RT decreased in all cases, with a greater reduction in the exposed groups compared to the control group. These results suggest that methylmercury exposure may cause cognitive impairment, yet it also possesses plasticity. Full article
(This article belongs to the Special Issue Health Effects of Exposure to Environmental Pollutants—2nd Edition)
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21 pages, 4988 KiB  
Article
Ozone Exposure Induces Prediabetic Symptoms Through Hepatic Glycogen Metabolism and Insulin Resistance
by Yuchai Tian, Xiaoyun Wu, Zhihua Gong, Xiaomin Liang, Huizhen Zhu, Jiyue Zhang, Yangcheng Hu, Bin Li, Pengchong Xu, Kaiyue Guo and Huifeng Yue
Toxics 2025, 13(8), 652; https://doi.org/10.3390/toxics13080652 - 31 Jul 2025
Viewed by 253
Abstract
(1) Background: Epidemiological studies link ozone (O3) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O3 were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related [...] Read more.
(1) Background: Epidemiological studies link ozone (O3) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O3 were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O3 exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O3-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O3 triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article
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12 pages, 418 KiB  
Article
Sarcopenia as a Prognostic Factor for Critical Limb Ischemia: A Prospective Cohort Study
by Paula Luque-Linero, Emilio-Javier Frutos-Reoyo, Luis Castilla-Guerra, Miguel-Ángel Rico-Corral, Prado Salamanca-Bautista and Fernando Garrachón-Vallo
J. Clin. Med. 2025, 14(15), 5388; https://doi.org/10.3390/jcm14155388 - 31 Jul 2025
Viewed by 234
Abstract
Introduction and Aim: Sarcopenia has emerged as a key prognostic factor in patients with chronic limb-threatening ischemia (CLTI), with potential implications for clinical decision-making. This study aimed to assess the association between sarcopenia and clinical outcomes, mortality, and amputation, using simple, accessible screening [...] Read more.
Introduction and Aim: Sarcopenia has emerged as a key prognostic factor in patients with chronic limb-threatening ischemia (CLTI), with potential implications for clinical decision-making. This study aimed to assess the association between sarcopenia and clinical outcomes, mortality, and amputation, using simple, accessible screening tools in a CLTI population. Methods: In this prospective, single-center study conducted between December 2023 and December 2024, 170 patients with CTLI were enrolled. Sarcopenia screening was performed using the SARC-F (strength, assistance in walking, rising from a chair, climbing stairs, falls) questionnaires, handgrip strength measurement, and calf circumference, adjusted for body mass index and sex. The primary outcome was 6-month all-cause mortality and/or major amputation. Results: Sarcopenia was identified in 77 patients (45.3%). Compared to non-sarcopenic individuals, sarcopenic patients were significantly older. They exhibited greater functional impairment, as well as poorer nutritional and muscle status. They also had significantly higher in-hospital mortality (16.9% vs. 3.2%, p = 0.002), 30-day mortality (24.7% vs. 4.3%, p = 0.001), and 6-month mortality (50.6% vs. 15.1%, p = 0.001). Sarcopenia was significantly associated with the primary outcome in univariate analysis (HR: 2.05; 95% CI: 1.31–3.20; p = 0.002) and remained an independent predictor after multivariate adjustment (HR: 1.95; 95% CI: 1.01–3.79; p = 0.048). Conclusions: Sarcopenia is a strong, independent predictor of poor outcome in patients with CLTI. Its detection through simple tools offers an easy and cost-effective strategy to improve risk stratification and guide early intervention through exercise-based therapy. Full article
(This article belongs to the Section Clinical Rehabilitation)
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32 pages, 2851 KiB  
Article
Characterization of Tellurite Toxicity to Escherichia coli Under Aerobic and Anaerobic Conditions
by Roberto Luraschi, Claudia Muñoz-Villagrán, Fabián A. Cornejo, Benoit Pugin, Fernanda Contreras Tobar, Juan Marcelo Sandoval, Jaime Andrés Rivas-Pardo, Carlos Vera and Felipe Arenas
Int. J. Mol. Sci. 2025, 26(15), 7287; https://doi.org/10.3390/ijms26157287 - 28 Jul 2025
Viewed by 246
Abstract
Tellurite (TeO32−) is a highly soluble and toxic oxyanion that inhibits the growth of Escherichia coli at concentrations as low as ~1 µg/mL. This toxicity has been primarily attributed to the generation of reactive oxygen species (ROS) during its intracellular [...] Read more.
Tellurite (TeO32−) is a highly soluble and toxic oxyanion that inhibits the growth of Escherichia coli at concentrations as low as ~1 µg/mL. This toxicity has been primarily attributed to the generation of reactive oxygen species (ROS) during its intracellular reduction by thiol-containing molecules and NAD(P)H-dependent enzymes. However, under anaerobic conditions, E. coli exhibits significantly increased tellurite tolerance—up to 100-fold in minimal media—suggesting the involvement of additional, ROS-independent mechanisms. In this study, we combined chemical-genomic screening, untargeted metabolomics, and targeted biochemical assays to investigate the effects of tellurite under both aerobic and anaerobic conditions. Our findings reveal that tellurite perturbs amino acid and nucleotide metabolism, leading to intracellular imbalances that impair protein synthesis. Additionally, tellurite induces notable changes in membrane lipid composition, particularly in phosphatidylethanolamine derivatives, which may influence biophysical properties of the membrane, such as fluidity or curvature. This membrane remodeling could contribute to the increased resistance observed under anaerobic conditions, although direct evidence of altered membrane fluidity remains to be established. Overall, these results demonstrate that tellurite toxicity extends beyond oxidative stress, impacting central metabolic pathways and membrane-associated functions regardless of oxygen availability. Full article
(This article belongs to the Section Molecular Microbiology)
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36 pages, 5612 KiB  
Review
The Multifaceted Role of p53 in Cancer Molecular Biology: Insights for Precision Diagnosis and Therapeutic Breakthroughs
by Bolong Xu, Ayitila Maimaitijiang, Dawuti Nuerbiyamu, Zhengding Su and Wenfang Li
Biomolecules 2025, 15(8), 1088; https://doi.org/10.3390/biom15081088 - 27 Jul 2025
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Abstract
The protein p53, often referred to as the “guardian of the genome,” is essential for preserving cellular balance and preventing cancerous transformations. As one of the most commonly altered genes in human cancers, its impaired function is associated with tumor initiation, development, and [...] Read more.
The protein p53, often referred to as the “guardian of the genome,” is essential for preserving cellular balance and preventing cancerous transformations. As one of the most commonly altered genes in human cancers, its impaired function is associated with tumor initiation, development, and resistance to treatment. Exploring the diverse roles of p53, which include regulating the cell cycle, repairing DNA, inducing apoptosis, reprogramming metabolism, and modulating immunity, provides valuable insights into cancer mechanisms and potential treatments. This review integrates recent findings on p53′s dual nature, functioning as both a tumor suppressor and an oncogenic promoter, depending on the context. Wild-type p53 suppresses tumors by inducing cell cycle arrest or apoptosis in response to genotoxic stress, while mutated variants often lose these functions or gain novel pro-oncogenic activities. Emerging evidence highlights p53′s involvement in non-canonical pathways, such as regulating tumor microenvironment interactions, metabolic flexibility, and immune evasion mechanisms. For instance, p53 modulates immune checkpoint expression and influences the efficacy of immunotherapies, including PD-1/PD-L1 blockade. Furthermore, advancements in precision diagnostics, such as liquid biopsy-based detection of p53 mutations and AI-driven bioinformatics tools, enable early cancer identification and stratification of patients likely to benefit from targeted therapies. Therapeutic strategies targeting p53 pathways are rapidly evolving. Small molecules restoring wild-type p53 activity or disrupting mutant p53 interactions, such as APR-246 and MDM2 inhibitors, show promise in clinical trials. Combination approaches integrating gene editing with synthetic lethal strategies aim to exploit p53-dependent vulnerabilities. Additionally, leveraging p53′s immunomodulatory effects through vaccine development or adjuvants may enhance immunotherapy responses. In conclusion, deciphering p53′s complex biology underscores its unparalleled potential as a biomarker and therapeutic target. Integrating multi-omics analyses, functional genomic screens, and real-world clinical data will accelerate the translation of p53-focused research into precision oncology breakthroughs, ultimately improving patient outcomes. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Cancer Treatment)
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