Search Results (147)

Myocardial injury following polytrauma is a significant yet often underdiagnosed condition that contributes to acute cardiac dysfunction and long-term cardiovascular complications. This review examines the role of systemic inflammation, oxidative stress, neuro-hormonal activation, and immune dysregulation in trauma-induced myocardial damage. Key immunological markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecules (ICAM-1, VCAM-1), are implicated in endothelial dysfunction, myocardial apoptosis, and ventricular remodeling. The interplay between these factors potentially exacerbates cardiac injury, increasing the risk of heart failure. Biomarker-guided approaches for early detection, combined with advanced imaging techniques such as speckle-tracking echocardiography and cardiac MRI, offer promising avenues for risk stratification and targeted interventions. Anti-inflammatory and oxidative stress-modulating therapies may mitigate myocardial damage and improve outcomes. This article highlights the clinical relevance of integrating immunological markers into diagnostic and therapeutic strategies to enhance the management of trauma-related cardiac dysfunction and reduce long-term morbidity. Full article

Neuro-oncology focuses on the diagnosis and treatment of brain tumors, which, despite their rarity, are associated with high mortality due to their invasiveness and limited treatment options. Emerging evidence suggests that dopamine (DA), a neurotransmitter crucial for cognitive and emotional processes, and its receptors may influence tumor growth and the tumor microenvironment. This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. The drugs were first tested individually, followed by co-treatment with tyrosine (Tyr), a dopamine precursor, and hydrogen peroxide (H₂O₂), an inducer of oxidative stress. Additionally, drug activity was evaluated in the simultaneous presence of H₂O₂ and Tyr. CLZ exhibited the highest cytotoxicity in both cell lines, suggesting strong anticancer potential and also synergism among the different combinations, particularly in SH-SY5Y. Liquid chromatography of the extracellular medium showed greater Tyr consumption in SH-SY5Y compared to A172 cells, indicating a higher dependence on extracellular Tyr to mitigate drug- and/or stress-induced cytotoxicity. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology. Full article

Obstructive sleep apnoea (OSA) is a prevalent condition characterised by intermittent upper airway obstruction during sleep, resulting in recurrent hypoxia and sleep fragmentation. Emerging evidence highlights the significant impact of OSA on neuro-ophthalmological health, linking it to conditions such as glaucoma, optic neuropathy, papilledema, and visual field defects. These associations emphasise the importance of understanding the mechanisms connecting OSA to neuro-ophthalmological disorders to enhance early diagnosis and management. This review explores the pathophysiological pathways, including hypoxia-induced vascular dysregulation, oxidative stress, inflammation, and intracranial pressure fluctuations, that contribute to ocular and neurological impairments in OSA patients. Advanced diagnostic tools, such as optical coherence tomography and polysomnography, offer promising avenues for detecting subclinical neuro-ophthalmological changes, enabling timely intervention. Management strategies, primarily centred on continuous positive airway pressure therapy, have shown efficacy in mitigating OSA-related neuro-ophthalmological complications. However, surgical and pharmacological interventions and lifestyle modifications remain vital components of a multidisciplinary approach to care. Despite advancements, significant research gaps persist, particularly in understanding the long-term impact of OSA treatment on neuro-ophthalmological outcomes and identifying specific biomarkers for early detection. Future research should prioritise longitudinal studies, interdisciplinary collaborations, and personalised medicine approaches to address these challenges. Recognising and treating neuro-ophthalmological disorders in OSA patients is imperative for improving quality of life and preventing irreversible visual and neurological damage. Full article

Post-traumatic cardiac dysfunction is a clinically under-recognized complication of polytrauma, often occurring in the absence of overt structural injury. Traditional diagnostic tools frequently fail to detect early or subclinical myocardial impairment, underscoring the need for more sensitive assessment methods. This review explores the utility of global longitudinal strain (GLS), derived from speckle-tracking echocardiography (STE), as a sensitive biomarker for identifying and managing cardiac dysfunction following traumatic injury. It outlines the complex pathophysiology of trauma-induced myocardial impairment, including mechanical injury, systemic inflammation, oxidative stress, and neuro-hormonal activation. The limitations of conventional diagnostic approaches, such as electrocardiography, left ventricular ejection fraction (LVEF), and cardiac biomarkers, are critically assessed and contrasted with the enhanced diagnostic performance of GLS. GLS has demonstrated superior sensitivity in detecting subclinical myocardial dysfunction even when LVEF remains preserved and is associated with increased risk of long-term cardiovascular complications, including arrhythmias and heart failure. The manuscript highlights the clinical utility of GLS in early diagnosis, risk stratification, treatment monitoring, and long-term follow-up. Integration of GLS with inflammatory and oxidative biomarkers (e.g., IL-6, TNF-α, and MPO) and artificial intelligence-based diagnostic models offers potential for improved precision in trauma cardiology. Full article

Current treatments fail to prevent long-term consequences induced by a severe traumatic brain injury (TBI). This study aimed to evaluate the efficacy of repetitive intranasal administration of NeuroEPO (a derivative of erythropoietin) on long-term alterations after a severe TBI induced by the application of a lateral fluid percussion in male rats. A otal of 30–31 days after the trauma, TBI+vehicle group showed sensorimotor dysfunction (Neuroscore, p < 0.0009; beam walking test, p < 0.0001 vs. Sham+vehicle group) and depressive-like behavior suggested by increased immobility (p = 0.0009 vs. baseline) during the forced swim test. Rats also showed increased production of malondialdehyde (a marker of oxidative damage), increased catalase activity (an antioxidant enzyme), and atrophy of brain areas evaluated with Magnetic Resonance Imaging 31 days after the trauma. TBI+NeuroEPO group received intranasal administration of NeuroEPO (0.136 mg/kg) starting 3 h post-TBI and continued every 8 h for four days. This group showed less sensorimotor dysfunction (Neuroscore, p = 0.020; beam walking test, p = 0.001, vs. TBI+vehicle group) and normal immobility behavior (p = 0.998 vs. Sham+vehicle group). Levels of malondialdehyde and catalase as well as the volume of brain structures of this group were like the Sham+vehicle group. These findings support the potential of NeuroEPO as a therapeutic agent to reduce long-term consequences of TBI. Full article

Traumatic brain injury (TBI) in the elderly is frequently associated with worsened neurological outcomes and prolonged recovery, yet the age-specific molecular mechanisms driving this vulnerability remain poorly understood. Aging is characterized by increased oxidative stress and chronic neuro-inflammation, both of which may amplify the brain’s susceptibility to injury. In this study, we identify spermine oxidase (SMOX), a polyamine-catabolizing enzyme that produces reactive oxygen species, as a key mediator linking oxidative stress and neuro-inflammation to age-dependent TBI susceptibility. Using a mouse model of controlled cortical impact (CCI), we found that SMOX expression was significantly upregulated in aged brains, primarily in neurons and microglia, and this increase correlated with greater microglial activation, elevated pro-inflammatory cytokine expression, and widespread neuronal degeneration. Notably, SMOX upregulation also impaired astrocytic glutamate clearance by disrupting the membrane localization of the transporter GLT-1, contributing to excitotoxic stress. Importantly, analysis of postmortem human brain samples and transcriptomic data revealed a parallel age-related increase in SMOX expression, supporting its translational relevance. The pharmacological inhibition of SMOX with JNJ-9350 in aged mice reduced oxidative and inflammatory markers, preserved neuronal viability, and improved motor, cognitive, and emotional outcomes up to 30 days post-injury. These findings establish SMOX as a critical molecular driver of age-related vulnerability to TBI and highlight its inhibition as a promising therapeutic strategy for improving outcomes in elderly TBI patients. Full article

Pain is a significant global public health issue that can interfere with daily activities, sleep, and interpersonal relationships when it becomes chronic or worsens, ultimately impairing quality of life. Despite ongoing efforts, the efficacy of pain treatments in improving outcomes for patients remains limited. At present, the challenge lies in developing a personalized care and management plan that helps to maintain patient activity levels and effectively manages pain. Neuropathic pain is a chronic condition resulting from damage to the somatosensory nervous system, significantly impacting quality of life. It is partly thought to be caused by inflammation and oxidative stress, and clinical research has suggested a link between this condition and diet. However, these links are not yet well understood and require further investigation to evaluate the pathways involved in neuropathic pain. Specifically, the question remains whether supplementation with dietary antioxidants, such as melatonin, could serve as a potential adjunctive treatment for neuropathic pain modulation. Melatonin, primarily secreted by the pineal gland but also produced by other systems such as the digestive system, is known for its anti-inflammatory, antioxidant, and anti-aging properties. It is found in various fruits and vegetables, and its presence alongside other polyphenols in these foods may enhance melatonin intake and contribute to improved health. The aim of this review is to provide an overview of neuropathic pain and examine the potential role of melatonin as an adjunctive treatment in a neuro-nutritional approach to pain management. Full article

Myricetin is a natural flavonoid with powerful antioxidant and anti-inflammatory potential commonly found in vegetables, fruits, nuts, and tea. The vital role of this flavonoid in the prevention and treatment of various diseases is evidenced by its ability to reduce inflammation and oxidative stress, maintain tissue architecture, and modulate cell signaling pathways. Thus, this review summarizes recent evidence on myricetin, focusing precisely on its mechanisms of action in various pathogenesis, including obesity, diabetes mellitus, arthritis, osteoporosis, liver, neuro, cardio, and reproductive system-associated pathogenesis. Moreover, it has been revealed that myricetin exhibits anti-microbial properties due to obstructive virulence factors, preventing biofilm formation and disrupting membrane integrity. Additionally, synergistic potential with other drugs and the role of myricetin-based nanoformulations in different diseases are properly discussed. This review seeks to increase the understanding of myricetin’s pharmacological potential in various diseases, principally highlighting its effective mechanisms of action. Further wide-ranging research, as well as more randomized and controlled clinical trial studies, should be executed to reconnoiter this compound’s therapeutic value, safety, and usefulness against various human pathogenesis. Full article

Background/Objectives: this study evaluated the differential effects of two distinct dietary nucleotide supplements, combined with spontaneous physical activity, on neuromuscular, cognitive, and metabolic adaptations in older adults. Methods: Sixty-nine physically independent older adults (aged 60–75 years) were randomly assigned to three groups: (1) a yeast nucleotides formulation (YN) standardized in a high content of free nucleotides (>40%) rich in all macro and micro nutrients naturally occurring in yeast cell (amino acids, minerals and B-group vitamin); (2) a neuro-based formulation (NF) consisting of a blend of monophosphate nucleotides 5′; or (3) a placebo. Participants maintained their spontaneous physical activities without structured exercise during a 10-week intervention. Assessments included physical function, cognitive performance, body composition, quality of life, and serum biomarkers of oxidative stress, inflammation, and neurogenesis. Results: Both nucleotide-supplemented groups demonstrated significant improvements compared to placebo in physical performance (p ≤ 0.045), cognitive function (Trail Making Test B [TMT-B]: p ≤ 0.012), oxidative stress biomarkers (p ≤ 0.048), inflammatory cytokines (p ≤ 0.023), and quality-of-life parameters (p ≤ 0.047). Body composition remained stable in supplemented groups, whereas placebo increased fat mass (5.04%) and decreased muscle mass (−2.18%). Conclusions: Dietary nucleotide supplementation enhances the benefits of spontaneous physical activity across all measured variables in older adults, highlighting nucleotides as promising nutritional support for healthy aging. YN exhibited a trend toward greater inflammatory modulation, whereas NF showed a tendency toward enhanced neurotrophic effects and functional improvements, with a statistically significant improvement in the Timed Up and Go Test (p = 0.014). These findings underscore the potential for tailored nucleotide-based interventions to optimize distinct physiological domains in aging populations. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain–gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD. Full article

Autism spectrum disorder (ASD) is associated with mitochondrial dysfunction, but studies demonstrating the efficacy of treatments are scarce. We sought to determine whether a mitochondrial-targeted dietary supplement designed for children with ASD improved mitochondrial function and ASD symptomatology using a double-blind placebo-controlled cross-over design. Sixteen children [mean age 9 years 4 months; 88% male] with non-syndromic ASD and mitochondrial enzyme abnormalities, as measured by MitoSwab (Religen, Plymouth Meeting, PA, USA), received weight-adjusted SpectrumNeeds^® (NeuroNeeds, Old Lyme, CT, USA) and QNeeds^® (NeuroNeeds, Old Lyme, CT, USA) and placebos matched on taste, texture and appearance during two separate 12-week blocks. Which product was received first was randomized. The treatment significantly normalized citrate synthase and complex IV activity as measured by the MitoSwab. Mitochondrial respiration of peripheral blood mononuclear cell respiration, as measured by the Seahorse XFe96 (Agilent, Santa Clara, CA, USA) with the mitochondrial oxidative stress test, became more resilient to oxidative stress after the treatment, particularly in children with poor neurodevelopment. The mitochondrial supplement demonstrated significant improvement in standardized parent-rated scales in neurodevelopment, social withdrawal, and hyperactivity with large effect sizes (Cohen’s d’ = 0.77–1.25), while changes measured by the clinical and psychometric instruments were not significantly different. Adverse effects were minimal. This small study on children with ASD and mitochondrial abnormalities demonstrates that a simple, well-tolerated mitochondrial-targeted dietary supplement can improve mitochondrial physiology and ASD symptoms. Further larger controlled studies need to verify and extend these findings. These findings are significant as children with ASD have few other effective treatments. Full article

This study investigated the neuroprotective activity of oligomeric stilbenes (OSs) derived from Alpha grape stems in various in vitro models of Parkinson’s disease (PD). Using neurotoxin-induced cellular models, including 1-methyl-4-phenylpyridine (MPP+), paraquat (PQ), 6-hydroxydopamine (6-OHDA), and rotenone, we screened the cytoprotective effects of ampelopsin A (1), ε-viniferin (2), vitisin D (3), vitisin A (4), α-viniferin (5), trans-vitisin B (6), cis-vitisin B (7), and melanoxylin A (8). The results demonstrate that certain stilbenes significantly enhanced cell viability and reduced reactive oxygen species (ROS) levels in neurotoxin-treated Neuro-2a cells. Notably, vitisin A and trans-vitisin B exhibited promising neuroprotective properties by decreasing mitochondrial ROS and cardiolipin peroxidation. This study highlights the potential of these compounds in mitigating oxidative stress and inflammation associated with PD. Additionally, we provided new insights into the antioxidant mechanisms of these stilbenes, including their direct ROS-scavenging abilities. Our findings contribute to the understanding of oligomeric stilbenes as potential therapeutic agents for the prevention and treatment of neurodegenerative diseases, particularly those associated with oxidative damage. Further research is warranted to explore its clinical applications and underlying mechanisms of action. Full article

Melatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of circadian rhythm, regulation of the immunological system, epilepsy control, delaying the aging process, and diminishing hormones related to cancer. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The results showed it can present scavenging of free radicals, reducing inflammatory cytokines, and modulating the immune system. Moreover, it can improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, and plaque formation. These effects result in neuro- and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may be more cost-effective and present fewer adverse events than synthetic. However, more clinical trials should be performed to show adequate doses, formulation, and treatment time. Full article

Oxidative stress plays a role in various pathophysiological diseases, including neurogenerative diseases, such as Alzheimer′s disease (AD), which is the most prevalent neuro-pathology in the aging population. Oxidative stress has been reported to be one of the earliest pathological alterations in AD. Additionally, it was demonstrated that in older adults, there is a loss of free radical scavenging ability. The Nrf2 transcription factor is a key regulator in antioxidant defense systems, but, with aging, both the amount and the transcriptional activity of Nrf2 decrease. With the available treatments for AD being poorly effective, reinforcing the antioxidant defense systems via the Nrf2 pathway may be a way to prevent and treat AD. To highlight the predominant role of Nrf2 signaling in defending against oxidative stress and, therefore, against neurotoxicity, we present an overview of the natural compounds that exert their own neuroprotective roles through the activation of the Nrf2 pathway. This review is an opportunity to promote a holistic approach in the treatment of AD and to highlight the need to further refine the development of new potential Nrf2-targeting drugs. Full article

Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear. We harvested the secretome from human mucosal OECs and characterized its protein content, identifying 709 proteins in the human OEC secretome from three donors in two passages. Thirty-nine proteins, including neurological-related proteins, such as profilin-1, and antioxidants, such as peroxiredoxin-1 and glutathione S-transferase, were shared between the six samples. The secretome consistently demonstrated potential effects such as antioxidant activity, neuronal differentiation, and quiescence exit of neural stem cells (NSCs). The total secretome produced by OECs protects NSCs from H₂O₂-induced reactive oxygen species accumulation. During induction of neuronal differentiation, secretomes promoted neurite outgrowth, axon elongation, and expression of neuronal markers. The secretome ameliorated bone morphogenetic protein 4- and fibroblast growth factor 2-induced quiescence of NSCs. The human OEC secretome triggers NSCs to exit prime quiescence, which is related to increased phosphoribosomal protein S6 expression and RNA synthesis. The human OEC secretome has beneficial effects on NSCs and may be applied in neurological disease studies. Full article