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Search Results (1,413)

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Keywords = cognitive metabolism

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297 KiB  
Proceeding Paper
Patterns of Supplement Consumption and Interaction Risks Among Polymedicated Older Adults: A Descriptive Study
by Maria Deolinda Auxtero and Ana Isabel Fernandes
Med. Sci. Forum 2025, 37(1), 4; https://doi.org/10.3390/msf2025037004 - 19 Aug 2025
Abstract
This study investigates the use of food supplements (FS) among polymedicated elderly individuals and assesses potential FS–drug interaction risks. A total of 98 community-dwelling older adults were surveyed and 18.4% reported FS use. FS were mostly used for musculoskeletal and cognitive support, with [...] Read more.
This study investigates the use of food supplements (FS) among polymedicated elderly individuals and assesses potential FS–drug interaction risks. A total of 98 community-dwelling older adults were surveyed and 18.4% reported FS use. FS were mostly used for musculoskeletal and cognitive support, with 71% having potential metabolic interactions via CYP enzymes or P-glycoprotein. Monthly costs reached €55. The findings reveal a complex interaction landscape and financial burden, underscoring the need for medication reviews and health literacy efforts to ensure safer FS use in older adults. This study aligns with One Health principles by linking clinical, social, and economic aspects of aging. Full article
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10 pages, 507 KiB  
Review
Multiorgan Involvement and Particularly Liver Injury in Long COVID: A Narrative Review
by Carmen-Elena Florea, Bianca Bălaș-Maftei, Alexandra Rotaru, Patricia Lorena Adudanii, Stefana Teodora Vieru, Maria Grigoriu, Adelina Stoian and Carmen Manciuc
Life 2025, 15(8), 1314; https://doi.org/10.3390/life15081314 - 19 Aug 2025
Abstract
Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent [...] Read more.
Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent research has also found multiple organ systems, including the liver, to be significant sites of ongoing injury. This narrative review summarizes current knowledge on organ involvement during and after COVID-19, with particular focus on early and delayed hepatic manifestations and associated risk factors. Pathogenesis appears to be multifactorial, involving direct virus action, the body’s immune-mediated inflammatory response, microvascular damage, drug-induced hepatotoxicity, and, in some cases, reactivation or exacerbation of pre-existing liver conditions. The hepatic clinical manifestations range from asymptomatic elevations of transaminases to cholangiopathy and even fibrosis. These can persist or progress for months after the initial infection with SARS-CoV-2 is resolved, requiring prolonged monitoring and interdisciplinary care, especially in the presence of metabolic disorders, obesity, or hepatitis. Neurological, cardiovascular, and other sequelae are discussed in parallel, with attention paid to common inflammatory and thrombotic pathways. This review concludes that liver dysfunction is of particular interest in long-COVID due to the liver’s central role in metabolism and inflammation. While further research is being conducted into organ-specific and systemic interactions, the available evidence makes a compelling case for extended monitoring and integrated management strategies post infection. Full article
(This article belongs to the Special Issue Human Health Before, During, and After COVID-19)
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14 pages, 1330 KiB  
Article
Synergistic Effects of MTHFR, MTRR, and MTR Gene Variants on Serum Folate Levels and Cognitive Function in Chinese Preschoolers: A Cross-Sectional Study
by Lingling Ou, Luolan Peng, Jingbo Wang, Chao Han, Xiayu Zhao, Mengyao Wang, Mengtian Wang, Zhaolong Gong and Yan Li
Nutrients 2025, 17(16), 2666; https://doi.org/10.3390/nu17162666 - 18 Aug 2025
Viewed by 2
Abstract
Background/Objectives: Subnormal folate levels have a detrimental impact on the growth and development of preschoolers. We aimed to investigate the association between independent/synergistic effects of the gene polymorphisms (methyltetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms, alongside methionine synthase reductase (MTRR) A66G polymorphism [...] Read more.
Background/Objectives: Subnormal folate levels have a detrimental impact on the growth and development of preschoolers. We aimed to investigate the association between independent/synergistic effects of the gene polymorphisms (methyltetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms, alongside methionine synthase reductase (MTRR) A66G polymorphism and the methionine synthase (MTR) A2756G polymorphism) and serum folate levels as well as cognitive levels in Chinese preschoolers aged 5–7 years. Methods: Data were sourced from 614 children, acquired through the “Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack (LHEAITNP)” program were used. Folate serum concentrations were measured using a microbiologically modified technique. The genotypes of MTHFR A1298C and C677T, together with MTRR A66G, were identified by Kramer’s Allele-Specific PCR (KASP) technique. The cognitive scores of children were assessed by questionnaire. Results: MTHFR 677TT and MTR 2756AG + GG correlated negatively with serum folate levels (TT vs. CC + CT, p = 0.0009 and AG + GG vs. AA, p = 0.0057, respectively). MTHFR C677T and A1298C were independently linked to an elevated risk of suboptimal cognitive development (TT vs. CC + CT, p = 0.0009 and AA vs. CA + CC, p < 0.0001, respectively). The joint impact of these risk genotypes showed significantly increased risk of folate deficiency and inferior cognitive function compared to non-risk genotypes, particularly in those with more than two risk genotypes. The findings were corroborated by a cumulative effects model (p < 0.05). Conclusions: Our results indicate the substantial association between folate-homocysteine metabolism gene variants and serum folate status/cognitive performance in Chinese preschoolers. Potential gene-nutrient interactions worthy of longitudinal investigation. Full article
(This article belongs to the Section Pediatric Nutrition)
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37 pages, 2406 KiB  
Review
Apolipoprotein A (ApoA) in Neurological Disorders: Connections and Insights
by Humam Emad Rajha, Ahmed Hassanein, Rowan Mesilhy, Zainab Nurulhaque, Nebras Elghoul, Patrick G. Burgon, Rafif Mahmood Al Saady and Shona Pedersen
Int. J. Mol. Sci. 2025, 26(16), 7908; https://doi.org/10.3390/ijms26167908 - 16 Aug 2025
Viewed by 188
Abstract
Apolipoprotein A (ApoA) proteins, ApoA-I, ApoA-II, ApoA-IV, and ApoA-V, play critical roles in lipid metabolism, neuroinflammation, and blood–brain barrier integrity, making them pivotal in neurological diseases such as Alzheimer’s disease (AD), stroke, Parkinson’s disease (PD), and multiple sclerosis (MS). This review synthesizes current [...] Read more.
Apolipoprotein A (ApoA) proteins, ApoA-I, ApoA-II, ApoA-IV, and ApoA-V, play critical roles in lipid metabolism, neuroinflammation, and blood–brain barrier integrity, making them pivotal in neurological diseases such as Alzheimer’s disease (AD), stroke, Parkinson’s disease (PD), and multiple sclerosis (MS). This review synthesizes current evidence on their structural and functional contributions to neuroprotection, highlighting their dual roles as biomarkers and therapeutic targets. ApoA-I, the most extensively studied, exhibits anti-inflammatory, antioxidant, and amyloid-clearing properties, with reduced levels associated with AD progression and cognitive decline. ApoA-II modulates HDL metabolism and stroke risk, while ApoA-IV influences neuroinflammation and amyloid processing. ApoA-V, although less explored, is implicated in stroke susceptibility through its regulation of triglycerides. Genetic polymorphisms (e.g., APOA1 rs670, APOA5 rs662799) further complicate disease risk, showing population-specific associations with stroke and neurodegeneration. Therapeutic strategies targeting ApoA proteins, including reconstituted HDL, mimetic peptides, and gene-based approaches, show promise in preclinical models but face translational challenges in human trials. Clinical trials, such as those with CSL112, highlight the need for neuro-specific optimization. Further research should prioritize human-relevant models, advanced neuroimaging techniques, and functional assays to elucidate ApoA mechanisms inside the central nervous system. The integration of genetic, lipidomic, and clinical data offers potential for enhancing precision medicine in neurological illnesses by facilitating the generation of ApoA-targeted treatments and bridging current deficiencies in disease comprehension and therapy. Full article
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15 pages, 773 KiB  
Article
The Influence of Uric Acid Concentration on the Daily Functioning of Patients at an Advanced Age, Based on the Results of Selected Point Scales Routinely Used for the Comprehensive Geriatric Assessment in Poland
by Jakub Husejko, Mariusz Kozakiewicz, Marcin Gackowski, Katarzyna Mądra-Gackowska, Jakub Wojtasik, Iga Hołyńska-Iwan, Mateusz Porada, Magdalena Kiełkucka, Karol Harmoza, Anna Pokrzywa, Maja Kubiaczyk, Albert Jaśniak and Kornelia Kędziora-Kornatowska
J. Clin. Med. 2025, 14(16), 5793; https://doi.org/10.3390/jcm14165793 - 15 Aug 2025
Viewed by 233
Abstract
Background/Objectives: The concentration of uric acid in the body of older adults may have various effects. Due to the multidirectional influence on metabolism, its significance in the daily functioning of older persons remains unclear. The present investigation explored whether serum uric acid [...] Read more.
Background/Objectives: The concentration of uric acid in the body of older adults may have various effects. Due to the multidirectional influence on metabolism, its significance in the daily functioning of older persons remains unclear. The present investigation explored whether serum uric acid levels are associated with scores on standard geriatric assessment scales in hospitalized older adults. Methods: In total, 77 patients admitted to the hospital for the Comprehensive Geriatric Assessment were recruited and classified into three groups: successfully treated for hyperuricemia, untreated or unsuccessfully treated with elevated uric acid levels, and untreated controls having normal uric acid levels. The analysis considered the relationship between the concentration of uric acid in patients from different study groups and the assigned classes defined by the ranges of the questionnaires used for the study. Results: Significant differences were shown in the distribution of classes defined by Addenbrooke’s Cognitive Examination III (ACE-III) and the MNA questionnaires concerning the study groups. Moreover, significant differences were confirmed when using compartmentalization based only on the screening test results for the ACE-III, the Mini Nutritional Assessment (MNA), and the Mini-Mental State Examination (MMSE). For ACE-III, a lower percentage of people with probable dementia was observed in the control group (34.5%) than in the group with elevated uric acid values (78.3%). Conclusions: Although the mechanisms related to uric acid’s influence on older people’s functioning require further research, the available evidence indicates a negative impact of elevated uric acid levels on cognitive functions and the nutritional status of older individuals. Full article
(This article belongs to the Section Geriatric Medicine)
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44 pages, 3081 KiB  
Review
From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer’s Disease Landscape
by Anastasia Bougea, Manuel Debasa-Mouce, Shelly Gulkarov, Mónica Castro-Mosquera, Allison B. Reiss and Alberto Ouro
Medicina 2025, 61(8), 1462; https://doi.org/10.3390/medicina61081462 - 14 Aug 2025
Viewed by 386
Abstract
Background and Objectives: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer’s disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of [...] Read more.
Background and Objectives: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer’s disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of biomarkers in enhancing the diagnostic accuracy of AD, highlighting the major strides that have been made in recent years; (b) the role of neuropsychological testing in identifying biomarkers of AD, including the relationship between cognitive performance and neuroimaging biomarkers; (c) the amyloid hypothesis and possible molecular mechanisms of AD; and (d) the innovative AD therapeutics and the challenges and limitations of AD research. Materials and Methods: We have searched PubMed and Scopus databases for peer-reviewed research articles published in English (preclinical and clinical studies as well as relevant reviews and meta-analyses) investigating the molecular mechanisms, biomarkers, and treatments of AD. Results: Genome-wide association studies (GWASs) discovered 37 loci associated with AD risk. Core 1 biomarkers (α-amyloid Aβ42, phosphorylated tau, and amyloid PET) detect early AD phases, identifying both symptomatic and asymptomatic individuals, while core 2 biomarkers inform the short-term progression risk in individuals without symptoms. The recurrent failures of Aβ-targeted clinical studies undermine the amyloid cascade hypothesis and the objectives of AD medication development. The molecular mechanisms of AD include the accumulation of amyloid plaques and tau protein, vascular dysfunction, neuroinflammation, oxidative stress, and lipid metabolism dysregulation. Significant advancements in drug delivery technologies, such as focused Low-Ultrasound Stem, T cells, exosomes, nanoparticles, transferin, nicotinic and acetylcholine receptors, and glutathione transporters, are aimed at overcoming the BBB to enhance treatment efficacy for AD. Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. BACE inhibitors have been explored as a therapeutic strategy for AD. Gene therapies targeting APOE using the CRISPR/Cas9 genome-editing system are another therapeutic avenue. Conclusions: Classic neurodegenerative biomarkers have emerged as powerful tools for enhancing the diagnostic accuracy of AD. Despite the supporting evidence, the amyloid hypothesis has several unresolved issues. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments. Full article
(This article belongs to the Section Neurology)
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21 pages, 1321 KiB  
Review
Neurotransmitter Alterations in Prediabetes and Type 2 Diabetes Mellitus: A Narrative Review
by Roxana-Viorela Ahrițculesei, Lidia Boldeanu, Anda Lorena Dijmărescu, Mohamed-Zakaria Assani, Mihail Virgil Boldeanu, Isabela Siloși and Cristin Constantin Vere
Int. J. Mol. Sci. 2025, 26(16), 7847; https://doi.org/10.3390/ijms26167847 - 14 Aug 2025
Viewed by 175
Abstract
Prediabetes and early type 2 diabetes mellitus (T2D) are increasingly recognized as states of both metabolic and neurochemical dysregulation. This narrative review synthesizes emerging evidence of alterations in key neurotransmitter systems—dopamine, serotonin, norepinephrine, gamma-aminobutyric acid, and glutamate—in individuals with prediabetes and diabetes. Beyond [...] Read more.
Prediabetes and early type 2 diabetes mellitus (T2D) are increasingly recognized as states of both metabolic and neurochemical dysregulation. This narrative review synthesizes emerging evidence of alterations in key neurotransmitter systems—dopamine, serotonin, norepinephrine, gamma-aminobutyric acid, and glutamate—in individuals with prediabetes and diabetes. Beyond peripheral insulin resistance and β-cell dysfunction, disturbances in the central nervous system, especially related to neurotransmitter signaling, may play a role in disease onset and progression. Neuroimaging studies reveal early imbalances in excitatory and inhibitory neurotransmitters, while biochemical and histological findings demonstrate altered receptor expression in both the brain and pancreatic islets. These changes affect metabolic control and are implicated in mood, cognition, and feeding behavior. We investigate the mechanistic links between neurotransmitter dysfunction and glucose metabolism, including the roles of brain insulin resistance, inflammation, mitochondrial stress, and gut–brain axis signaling. Finally, we discuss therapeutic strategies that target neurochemical pathways and highlight the need for longitudinal, sex-aware, and multi-omics studies to refine early interventions. Understanding the neurobiological roots of early T2D could revolutionize risk assessment and open doors for new neuro-metabolic treatments. Full article
(This article belongs to the Special Issue Diabetes and Metabolic Dysfunction)
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31 pages, 4259 KiB  
Article
Neuronal Count, Brain Injury, and Sustained Cognitive Function in 5×FAD Alzheimer’s Disease Mice Fed DHA-Enriched Diets
by Cristina de Mello-Sampayo, Mafalda Soares Pádua, Maria Rosário Silva, Maria Lourenço, Rui M. A. Pinto, Sandra Carvalho, Jorge Correia, Cátia F. Martins, Romina Gomes, Ana Gomes-Bispo, Cláudia Afonso, Carlos Cardoso, Narcisa Bandarra and Paula A. Lopes
Biomolecules 2025, 15(8), 1164; https://doi.org/10.3390/biom15081164 - 14 Aug 2025
Viewed by 313
Abstract
Alzheimer’s disease (AD) is the most common form of dementia, affecting over 50 million people globally. Since 1906, efforts to understand this neurodegenerative disease and to develop effective treatments have continued to this day. Recognizing docosahexaenoic acid (DHA, 22:6n-3) as a safe, inexpensive [...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia, affecting over 50 million people globally. Since 1906, efforts to understand this neurodegenerative disease and to develop effective treatments have continued to this day. Recognizing docosahexaenoic acid (DHA, 22:6n-3) as a safe, inexpensive and vital nutrient for brain health and cognitive protection due to its key role in brain development and function, this study explores novel, sustainable non-fish sources as potential dietary supplements to prevent or mitigate AD, within a blue biotechnology framework. Forty 5×FAD male mice, five weeks old, were allocated to five body weight-matched dietary groups (n = 8) and fed isocaloric diets based on AIN-93M standard chow for 6 months. Each diet, except the control feed (non-supplemented group), enclosed a modified lipid fraction supplemented with 2% of the following: (1) linseed oil (LSO, rich in alpha-linolenic acid (ALA,18:3n-3)); (2) cod liver oil (fish oil, FO, rich in both DHA and eicosapentaenoic acid (EPA, 20:5n-3)); (3) Schizochytrium sp. microalga oil (Schizo) with 40% of DHA; and (4) commercial DHASCO oil (DHASCO) with 70% of DHA. The different diets did not affect (p > 0.05) growth performance criteria (e.g., final body weight, daily feed intake, and body weight gain) suggesting no effect on the overall caloric balance or mice growth, but n-3 long-chain polyunsaturated-fatty acid (n-3 LCPUFA) supplementation significantly reduced total cholesterol (p < 0.001) and total lipids (p < 0.001). No systemic inflammation was detected in 5×FAD mice. In parallel, a beneficial modulation of lipid metabolism by DHA-enriched diets was observed, with polyunsaturated fatty acid incorporation, particularly DHA, across key metabolic tissues, such as the liver (p < 0.001) and the brain (p < 0.001). No behavioural variations were detected using an open-field test after 6 months of diet (p > 0.05). While mice fed a standard diet or LSO diet showed cognitive deficit, the incorporation of FO, Schizo or DHASCO oils into dietary routine showed promising protective effects on the working memory (p < 0.05) and the last two diets also on the recognition memory (p < 0.05) Increased neuronal count (p < 0.05), reflecting neuronal survival, was clearly observed with the fish oil diet. In turn, the number of TAU-positive cells (p < 0.05) was reduced in the Schizo diet, while β-amyloid deposition (p < 0.01) and the neuroinflammatory marker, IBA1 (p < 0.05), were decreased across all DHA-enriched diets. These promising findings open new avenues for further studies focused on the protective effects of DHA derived from sustainable and underexploited Schizochytrium sp. microalga in the prevention of AD. Full article
(This article belongs to the Section Cellular Biochemistry)
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25 pages, 2795 KiB  
Review
Precision Nutrition for Dementia: Exploring the Potential in Mitigating Dementia Progression
by Tara J. Jewell, Michelle Minehan, Jackson Williams and Nathan M. D’Cunha
J. Dement. Alzheimer's Dis. 2025, 2(3), 28; https://doi.org/10.3390/jdad2030028 - 14 Aug 2025
Viewed by 266
Abstract
Precision nutrition is a tailored dietary approach that considers an individual’s genetic and metabolic profile, lifestyle factors, and specific nutritional needs to improve health and potentially modify disease progression. While research is ongoing into precision nutrition approaches for preventing dementia, there is no [...] Read more.
Precision nutrition is a tailored dietary approach that considers an individual’s genetic and metabolic profile, lifestyle factors, and specific nutritional needs to improve health and potentially modify disease progression. While research is ongoing into precision nutrition approaches for preventing dementia, there is no evidence on its targeted application to slow dementia-related disease progression and mitigate functional and cognitive decline. This narrative review addresses this gap by synthesising evidence on nutrient–gene interactions, genotype, gut microbiome, nutritional status and the interplay between metabolic pathways implicated in neuroinflammation and neurodegeneration to modify disease progression in a protective or therapeutic manner. Understanding and addressing comorbidities that share pathological mechanisms with dementia have the potential to enhance the understanding of precision nutrition to inform more effective, tailored approaches to slow dementia progression. To increase the robustness of precision nutrition trials for people with dementia, further research is needed into biomarker discovery, multi-omics technologies, and increasing mechanistic research to map the precise biological pathways underpinning the interactions between diet, gene expression, and neuroinflammation. Moreover, there is a need to evaluate the feasibility of precision nutrition for people experiencing cognitive impairment. Addressing these gaps will determine if people with dementia can benefit from precision nutrition and, subsequently, improve their quality of life and health outcomes. Full article
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18 pages, 814 KiB  
Article
Dual Impact of Iron Deficiency and Antibiotics on Host Metabolism: A Tissue-Level Analysis
by Shannon Shoff, Sydney Thomas, Peng Ji, Mariana Parenti and Carolyn M. Slupsky
Metabolites 2025, 15(8), 549; https://doi.org/10.3390/metabo15080549 - 14 Aug 2025
Viewed by 243
Abstract
Background/Objectives: Iron deficiency (ID) is a common nutritional deficiency in infancy and early childhood associated with increased risk of infection and increased likelihood of receiving antibiotic intervention. In the context of ID, antibiotics have been shown to exaggerate the growth impairments and [...] Read more.
Background/Objectives: Iron deficiency (ID) is a common nutritional deficiency in infancy and early childhood associated with increased risk of infection and increased likelihood of receiving antibiotic intervention. In the context of ID, antibiotics have been shown to exaggerate the growth impairments and negative impacts on metabolic health of ID itself. The objective of this research was to assess the tissue-level impact of antibiotics when provided during ID. Methods: ID was induced in piglets by withholding an iron dextran shot shortly after birth, and iron deficiency was maintained after weaning by providing an iron-deficient diet starting on postnatal day (PD) 25. Half of the ID piglets received a 3-day antibiotic course (ID + Abx) consisting of spectinomycin and gentamicin from PD34-36. The kidney, liver, skeletal muscle, and hippocampal metabolomes, as well as activity of proteins in the mTOR signaling pathway, were assessed on PD43. Results: While ID had minimal impacts on the liver, kidney, and skeletal muscle metabolomes, ID + Abx impaired energy metabolism and increased ketosis and oxidative stress in peripheral tissues. Hippocampal metabolites involved in neurotransmitter synthesis pathways were affected by ID and ID + Abx to a greater extent. Additionally, the activities of several proteins in the mTOR pathway were upregulated in the hippocampi of ID + Abx piglets compared to both ID and control piglets. Abx provided to iron-sufficient piglets had minimal effects on tissue metabolomes and did not alter the activity of proteins in the mTOR pathway. Conclusions: These results highlight that antibiotic treatment in ID alters metabolism in peripheral tissues and the developing hippocampus beyond those induced by ID alone. Considering that infants and children are develop rapidly, the combination of ID and antibiotics may have lasting impacts on neurodevelopment and cognition. Full article
(This article belongs to the Section Nutrition and Metabolism)
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9 pages, 227 KiB  
Article
Sleep Disorders in Infants and Toddlers with Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia: A Case–Control Study Using the SDSC
by Domenico M. Romeo, Chiara Arpaia, Maria Rosaria Lala, Giorga Cordaro, Claudia Brogna, Marianna Moro, Francesca Gallini, Giovanni Vento and Eugenio Mercuri
Children 2025, 12(8), 1058; https://doi.org/10.3390/children12081058 - 12 Aug 2025
Viewed by 275
Abstract
Background and Objectives: Sleep complaints are particularly relevant in the development of children, affecting cognitive development, neuropsychological functioning, and learning abilities. The aims of this study were as follows: (i) to determine the incidence of sleep disorders in low-risk infants and toddlers with [...] Read more.
Background and Objectives: Sleep complaints are particularly relevant in the development of children, affecting cognitive development, neuropsychological functioning, and learning abilities. The aims of this study were as follows: (i) to determine the incidence of sleep disorders in low-risk infants and toddlers with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), using the Italian version of the Sleep Disturbance Scale for Children (SDSC); and (ii) to compare the data with those of a healthy control group. Materials and Methods: This is a cross-sectional case–control study involving a total of 167 infants and toddlers (aged 6–36 months) with HIE treated with TH and 160 typically developing infants assessed using the SDSC filled out by the mother. A neurocognitive assessment was also performed. Exclusion criteria were mild perinatal asphyxia, major brain lesions, congenital malformations, severe postnatal infectious diseases, metabolic complications, cerebral palsy, neurodevelopmental impairment, and epilepsy. Results: In the study group, an abnormal total SDSC score was found in 1.8% of infants; 10% of infants had an abnormal score on at least one of the SDSC factors. No specific differences in the SDSC total and the factor scores were observed between the study and control group, with the exception of difficulties in maintaining sleep and sleep hyperhidrosis, with higher scores in HIE infants. Conclusions: Low-risk infants and toddlers with HIE showed a low incidence of sleep disorders, similar to those observed in control group, with some exceptions. As these incidences may increase significantly with age, further clinical assessments will be needed to confirm these data at older ages. Full article
(This article belongs to the Section Pediatric Neurology & Neurodevelopmental Disorders)
16 pages, 859 KiB  
Review
Scoping Review: The Role of Tocotrienol-Rich Fraction as a Potent Neuroprotective Agent
by Elvira Yunita, Muhammad Luqman Nasaruddin, Nur Zuliani Ramli, Mohamad Fairuz Yahaya and Hanafi Ahmad Damanhuri
Int. J. Mol. Sci. 2025, 26(16), 7691; https://doi.org/10.3390/ijms26167691 - 8 Aug 2025
Viewed by 219
Abstract
Tocotrienol-rich fraction (TRF), a subtype of vitamin E, has recently been reported to demonstrate promising neuroprotective properties. However, it remains to be fully determined how it confers protection in the brain. This scoping review aimed to explore and understand the intricate role of [...] Read more.
Tocotrienol-rich fraction (TRF), a subtype of vitamin E, has recently been reported to demonstrate promising neuroprotective properties. However, it remains to be fully determined how it confers protection in the brain. This scoping review aimed to explore and understand the intricate role of TRF in promoting and preserving neuronal well-being. A systematic literature search, based on the framework by Arksey and O’Malley and adhering to the PRISMA-ScR guidelines, was conducted across several databases, including PubMed, Scopus, and Web of Science (WOS), using the following phrases and Boolean operators: (“tocotrienol-rich fraction”) AND ((“neuroprotect”) OR (“cognit”) OR (“brain”)). The search yielded a total of 24 eligible articles, shortlisted based on predetermined inclusion and exclusion criteria established at the outset of the study. The findings highlight a diverse array of TRF-related studies, both in vivo and in vitro, that revealed functional mechanisms through which TRF confers neuroprotection. These include, but are not limited to, antioxidant and anti-inflammatory effects via attenuation of superoxide dismutase (SOD) activity and pro-inflammatory mediators; regulation of metabolic pathways; regulation of neuronal genes, proteins, and maintenance of cellular functions; and subsequent improvements in memory and cognitive performance in animal models following TRF treatment. The convergence of these neuroprotective effects suggests that TRF holds potential as a supplement to support healthy ageing or, at the very least, slow neurodegeneration by mitigating pathological changes that often begin insidiously before the onset of symptoms associated with cognitive decline. Full article
(This article belongs to the Special Issue Natural Products for Neuroprotection and Neurodegeneration)
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16 pages, 918 KiB  
Systematic Review
Experimental Evidence of Caffeic Acid’s Neuroprotective Activity in Alzheimer’s Disease: In Vitro, In Vivo, and Delivery-Based Insights
by Adam Kowalczyk, Carlo Ignazio Giovani Tuberoso and Igor Jerković
Medicina 2025, 61(8), 1428; https://doi.org/10.3390/medicina61081428 - 8 Aug 2025
Viewed by 276
Abstract
Background and Objectives: Alzheimer’s disease (AD) is a complex neurodegenerative disorder marked by cholinergic deficits, oxidative stress, amyloid-β (Aβ) aggregation, and tau hyperphosphorylation. Caffeic acid (CA), a naturally occurring hydroxycinnamic acid, has emerged as a promising neuroprotective candidate due to its antioxidant, [...] Read more.
Background and Objectives: Alzheimer’s disease (AD) is a complex neurodegenerative disorder marked by cholinergic deficits, oxidative stress, amyloid-β (Aβ) aggregation, and tau hyperphosphorylation. Caffeic acid (CA), a naturally occurring hydroxycinnamic acid, has emerged as a promising neuroprotective candidate due to its antioxidant, anti-inflammatory, and enzyme-inhibitory properties. This review systematically evaluates recent in vitro and in vivo evidence regarding the therapeutic potential of CA in AD models and examines the impact of delivery systems and derivatives on its efficacy and bioavailability. Materials and Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases, adhering to the PRISMA 2020 guidelines. Studies published between January 2021 and April 2025 were included in this review. Eligible studies investigated the effects of CA or CA-enriched extracts on AD-relevant mechanisms using in vitro, in vivo, and in silico models. After screening 101 articles, 44 met the inclusion criteria and were included in the final qualitative synthesis of the study. Results: In vitro studies have confirmed that CA modulates cholinergic activity by inhibiting AChE and BChE and exerting antioxidant and anti-amyloidogenic effects. In vivo studies using pharmacological, genetic, and metabolic AD models have demonstrated improvements in cognitive function, reduction in oxidative stress, inflammation, and Aβ and tau pathologies following CA administration. Advanced delivery platforms, such as solid lipid nanoparticles, transferrin-functionalized liposomes, and carbon dot systems, have significantly enhanced CA’s brain bioavailability and therapeutic efficacy. CA derivatives, including caffeic acid phenethyl ester and nitro-substituted analogs, exhibit improved pharmacokinetic and neuroprotective profiles. Conclusions: This review provides evidence supporting the use of CA as a promising multitarget agent against AD pathology. Its therapeutic potential is further enhanced by nanotechnology-based delivery systems and chemical modifications that overcome the limitations of bioavailability. Continued preclinical evaluation and translational studies are warranted to support its clinical development as an AD intervention. Full article
(This article belongs to the Section Pharmacology)
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22 pages, 1229 KiB  
Article
Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia
by Ghazaleh Azimi, Wesam Elremaly, Mohamed Elbakry, Anita Franco, Christian Godbout and Alain Moreau
Int. J. Mol. Sci. 2025, 26(16), 7670; https://doi.org/10.3390/ijms26167670 - 8 Aug 2025
Viewed by 288
Abstract
Myalgic encephalomyelitis (ME) and fibromyalgia (FM) are overlapping syndromes characterized by persistent fatigue, cognitive difficulties, and post-exertional malaise (PEM), yet they lack objective biomarkers for diagnosis and treatment. Fibroblast growth factor 21 (FGF-21), a stress-responsive metabolic hormone, may offer a promising avenue to [...] Read more.
Myalgic encephalomyelitis (ME) and fibromyalgia (FM) are overlapping syndromes characterized by persistent fatigue, cognitive difficulties, and post-exertional malaise (PEM), yet they lack objective biomarkers for diagnosis and treatment. Fibroblast growth factor 21 (FGF-21), a stress-responsive metabolic hormone, may offer a promising avenue to distinguish subtypes within these patient populations. In this cross-sectional study, plasma FGF-21 levels were measured in 250 patients (FM = 47; ME = 99; ME + FM = 104) and 54 healthy controls. Participants were categorized based on FGF-21 levels into three groups: low (0–50 pg/mL), normal (51–200 pg/mL), and high (>200 pg/mL). Symptoms burden and cognitive function were assessed using validated questionnaires (SF-36, MFI-20, DSQ, DPEMQ) and the BrainCheck platform. A standardized mechanical provocation maneuver was used to induce PEM. Results showed that elevated FGF-21 levels were frequently observed in ME and ME + FM but varied widely across all groups. Stratification by circulating FGF-21 levels, rather than diagnosis alone, revealed distinct symptom and cognitive profiles. Low FGF-21 levels were linked to worsened PEM perception in FM, increased PEM severity and immune/autonomic symptoms in ME, and poorer mental health in ME + FM. Conversely, high FGF-21 levels correlated with better cognition in ME but greater fatigue in ME + FM. These findings suggest that FGF-21 may serve as a valuable biomarker for identifying clinically meaningful subtypes within ME and FM, supporting the development of personalized treatments. Furthermore, discrepancies between DSQ and DPEMQ highlight the need for objective PEM assessment tools. Overall, FGF-21 shows potential as a biomarker to guide precision medicine in these complex conditions. Full article
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Review
Molecular Links Between Metabolism and Mental Health: Integrative Pathways from GDF15-Mediated Stress Signaling to Brain Energy Homeostasis
by Minju Seo, Seung Yeon Pyeon and Man S. Kim
Int. J. Mol. Sci. 2025, 26(15), 7611; https://doi.org/10.3390/ijms26157611 - 6 Aug 2025
Viewed by 453
Abstract
The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact [...] Read more.
The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article
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