Search Results (1,190)

Doxorubicin (DOX) is widely used for the treatment of several tumors, but considerable dose-dependent side effects on many normal tissues, including bones, have been reported. The aim of the present study was to follow for the first time the kinetics of DOX accumulation/clearance in the non-vascularized intervertebral disc (IVD), as well as to assess the drug’s biological action in the annulus fibrosus (AF) and nucleus pulposus (NP) IVD cells and tissues. DOX was administered intravenously to rabbits before the isolation of IVDs, in which DOX quantification was performed using a highly sensitive LC-HRMS/MS analytical method. The effect of the drug on IVD cells’ physiology was assessed in vitro, while IVD tissue quality post-DOX administration was studied in vivo through histological analysis. DOX delivery was found significantly lower in the IVD compared to the highly vascularized skin, declining from the outer AF to the inner NP. The low DOX concentrations reaching the IVDs had marginal effects on cells’ viability, intracellular redox status, and p38 MAPK activation, while they did not evoke cellular senescence. Most importantly, the drug did not negatively affect ECM integrity, as collagen and proteoglycan content remained stable in vitro and in vivo. Full article

Current research reported that the number of clinical studies found for botulinum toxin (BoNT) key effects on biochemical biomarkers in head and neck chronic conditions linked to inflammation was very low. There are no systematic reviews of animal studies on this topic, and hence our review aimed to evaluate the quality of the preclinical evidence. We searched PubMed, Scopus, and Web of Science databases, and registries up to 29 January 2024. There were 22 eligible records, and data were available for 11 randomised controlled trials. There were concerns about the risk of bias and great variations of data obtained regarding chronic conditions, which included mostly trigeminal neuralgia. The leading biomarkers were proinflammatory cytokines (IL-1β, TNF-α) and synaptosomal-associated protein-25 (SNAP25), followed by neuron activation marker c-Fos and calcitonin gene-related peptide (CGRP). Overall, data found that BoNT significantly altered the under/over-expression of biomarkers evoked by the investigated disease models and had no effect when the levels of these biomarkers were not changed by the induced chronic conditions in animals. However, there were some mixed results and exceptions, and the certainty evidence found was very low to low. Although the sample sizes detected significant effect size (p < 0.05), most studies are based on male inferior animals, which may limit the recommendations for clinical trials. This study is registered on PROSPERO (CRD42023432411). Full article

The venom of Bothrops jararaca (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model of BjV-evoked pain and inflammation. Mice received a single intraperitoneal (i.p.) injection of MaR2 30 min before the intraplantar BjV injection. MaR2 treatment significantly attenuated mechanical (electronic aesthesiometer) and thermal (hot plate) hyperalgesia in a dose-dependent manner. Additionally, MaR2 restored the balance for the hind-paw static weight distribution. When BjV (0.01, 0.1, and 1 μg) stimulus was administered intraperitoneally, pre-treatment with MaR2 (0.3, 1, or 3 ng) ameliorated mechanical and thermal hyperalgesia in a dose-dependent manner. Moreover, MaR2 (3 ng) effectively reduced the levels of myeloperoxidase activity and cytokines (TNF-α, IL-1β, and IL-6) and superoxide anion (O₂^•−) production induced by intraplantar injection of BjV while enhancing total antioxidant levels (ABTS scavenging). For the peritonitis model induced by BjV, MaR2 pretreatment decreased leukocyte recruitment, hemorrhage, nitric oxide (NO), and O₂^•− generation and gp91phox and inducible nitric oxide synthase (iNOS) mRNA expression. In conclusion, this study presents the first evidence that MaR2 effectively mitigated BjV-induced pain, hemorrhage, and inflammation. Full article

Car interior design should evoke emotions, offer comfort, convey safety and at the same time project the brand identity of the car manufacturer. Lighting is used to address these functions. Modules required for automotive interior lighting often feature injection-moulded (IM) light guides, whereas woven fabrics with polymer optical fibres (POFs) offer certain technological advantages and show first-series applications in cars. In the future, car interior illumination will become even more important in the wake of megatrends such as autonomous driving. Since the increase in deployment of these technologies facilitates a need for an economical comparison, this paper aims to deliver a cost-driven approach to fulfil the aforementioned objective. Therefore, the cost structures of the supply chains for an IM-based and a POF-based illumination module are analysed. The employed research methodologies include an activity-based costing approach for which the data is collected via document analysis and guideline-based expert interviews. To account for data uncertainty, Monte Carlo simulations are conducted. POF-based lighting modules have lower initial costs due to continuous fibre production and weaving processes, but are associated with higher unit costs. This is caused by the discontinuous assembly of the rolled woven fabric which allows postponement strategies. The development costs of the mould generate high initial costs for IM light guides, which makes them beneficial only for high quantities of produced light guides. For the selected scenario, the POF-based module’s self-costs are 11.05 EUR/unit whereas the IM module’s self-costs are 14,19 EUR/unit. While the cost structures are relatively independent from the selected scenario, the actual self-costs are highly dependent on boundary conditions such as production volume. Full article

Background/Objectives: Concussions have been associated with deficits in attentional control. The current work examined whether attentional correlates could be enhanced following acute aerobic exercise in those with a history of concussion (CH). Methods: EEG was collected as participants completed a flanker task to evoke stimulus-locked (N2, P3) and response-locked error-related (ERN, Pe) ERPs, before and after participants completed a bout of acute aerobic exercise at moderate intensity. Conflict was modulated with distance (close/far) and congruency (incongruent/congruent) of the distractors relative to the targets. Results: CH individuals had reduced accuracy in high-conflict conditions, with improvements following exercise. No differences were observed in attentional cognitive control across the four conditions (close/far congruent, close/far incongruent); however, reduced interference control was shown in far conditions, when compared to close conditions. When compared to non-concussed controls, increased accuracy with increased response time in individuals with a concussion history was likely attributed to the speed–accuracy trade-off. Close conditions highlighted a decreased Pe amplitude in CH individuals (as opposed to the active controls), suggesting CH individuals may present with challenges when evaluating an error with working memory. Conclusions: The findings demonstrated acute exercise improved accuracy among CH individuals, and performance monitoring is impacted negatively long term following a concussion. Full article

Industrial development has increased environmental dioxin concentrations, sparking concern about human health impacts. Examining dioxin neurotoxicity has highlighted associations with cognitive impairment and behavioral abnormality. Dioxins are ligands of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor; it is speculated that dioxin-induced AHR activation is pivotal for toxic effects. Accurate AHR-expressing cell identification is therefore indispensable for understanding the molecular and cellular mechanisms of dioxin toxicity. Herein, current knowledge regarding AHR expression in the mammalian brain is summarized, and dioxin neurotoxicity mechanisms are discussed. Histological studies show AHR-expressing neurons in multiple brain regions, including the hippocampus and cerebral cortex. Dopaminergic and noradrenergic neurons exhibit AHR expression, suggesting possible roles in the monoaminergic system. AHR overactivation evokes dendritic arborization atrophy, whereas its deficiency increases complexity, implying that AHR-mediated signaling is crucial for neuronal growth and maturation. AHR is also involved in neurogenesis and neuronal precursor migration. Collectively, these findings support the notion that dioxin-induced AHR overactivation in individual neurons disrupts neural circuit structure, ultimately leading to impaired brain function. However, as AHR downstream signaling is intertwined with various molecules and pathways, the precise mechanisms remain unclear. Further studies on the expression, signaling, and roles of AHR are needed to clarify dioxin neurotoxicity. Full article

Zebrafish (Danio rerio) combine accessible behavioral phenotypes with conserved neurochemical pathways and molecular features of vertebrate brain function, positioning them as a powerful model for investigating early neurodegenerative processes and screening neuroprotective strategies. In this context, integrated behavioral and proteomic analyses provide valuable insights into the initial pathophysiological events shared by conditions such as Parkinson’s disease and related disorders—including mitochondrial dysfunction, oxidative stress, and synaptic impairment—which emerge before overt neuronal loss and offer a crucial window to understand disease progression and evaluate therapeutic candidates prior to irreversible damage. To investigate this early window of dysfunction, zebrafish larvae were exposed to 500 μM 1-methyl-4-phenylpyridinium (MPP⁺) from 1 to 5 days post-fertilization and evaluated through integrated behavioral and label-free proteomic analyses. MPP⁺-treated larvae exhibited hypokinesia, characterized by significantly reduced total distance traveled, fewer movement bursts, prolonged immobility, and a near-complete absence of light-evoked responses—mirroring features of early Parkinsonian-like motor dysfunction. Label-free proteomic profiling revealed 40 differentially expressed proteins related to mitochondrial metabolism, redox regulation, proteasomal activity, and synaptic organization. Enrichment analysis indicated broad molecular alterations, including pathways such as mitochondrial translation and vesicle-mediated transport. A focused subset of Parkinsonism-related proteins—such as DJ-1 (PARK7), succinate dehydrogenase (SDHA), and multiple 26S proteasome subunits—exhibited coordinated dysregulation, as visualized through protein–protein interaction mapping. The upregulation of proteasome components and antioxidant proteins suggests an early-stage stress response, while the downregulation of mitochondrial enzymes and synaptic regulators reflects canonical PD-related neurodegeneration. Together, these findings provide a comprehensive functional and molecular characterization of MPP⁺-induced neurotoxicity in zebrafish larvae, supporting its use as a relevant in vivo system to investigate early-stage Parkinson’s disease mechanisms and shared neurodegenerative pathways, as well as for screening candidate therapeutics in a developmentally responsive context. Full article

The objective of this study was to analyze the impact of solar and hybrid dryers on the physicochemical characteristics, fingerprints, and cognitive-sensory perceptions of Mexican consumers of traditional tostadas made with corn of different races. Corn tostadas from different native races were evaluated with solar and hybrid (solar-photovoltaic solar panels) dehydration methods. Proximal chemical quantification, instrumental analysis (color, texture), fingerprint by Fourier transform infrared spectroscopy (FTIR), and sensory-cognitive profile (emotions and memories) and its relationship with the level of pleasure were carried out. The data were evaluated using analysis of variance models, Cochran Q, and an external preference map (PREFMAP). The results showed that the drying method and corn race significantly (p < 0.05) affected only moisture content, lipids, carbohydrates, and water activity. Instrumental color was influenced by the corn race effect, and the dehydration type influenced the fracturability effect. FTIR fingerprinting results revealed that hybrid samples exhibited higher intensities, particularly associated with higher lime concentrations, indicating a greater exposure of glycosidic or protein structures. Race and dehydration type effects impacted the intensity of sensory attributes, emotions, and memories. PREFMAP vector model results revealed that consumers preferred tostadas from the Solar-Chiquito, Hybrid-Pepitilla, Hybrid-Cónico, and Hybrid-Chiquito races for their higher protein content, moisture, high fracturability, crunchiness, porousness, sweetness, doughy flavor, corn flavor, and burnt flavor, while images of these tostadas evoked positive emotions (tame, adventurous, free). In contrast, the Solar-Pepitilla tostada had a lower preference because it was perceived as sour and lime-flavored, and its tostada images evoked more negative emotions and memories (worried, accident, hurt, pain, wild) and fewer positive cognitive aspects (joyful, warm, rainy weather, summer, and interested). However, the tostadas of the Solar-Cónico race were the ones that were most rejected due to their high hardness and yellow to blue tones and for evoking negative emotions (nostalgic and bored). Full article

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) has emerged as a transformative tool for probing cortical dynamics with millisecond precision. This review examines the state-dependent nature of TMS-EEG, a critical yet underexplored dimension influencing measurement reliability and clinical applicability. By integrating TMS’s neuromodulatory capacity with EEG’s temporal resolution, this synergy enables real-time analysis of brain network dynamics under varying neural states. We delineate foundational mechanisms of TMS-evoked potentials (TEPs), discuss challenges posed by temporal and inter-individual variability, and evaluate advanced paradigms such as closed-loop and task-embedded TMS-EEG. The former leverages real-time EEG feedback to synchronize stimulation with oscillatory phases, while the latter aligns TMS pulses with task-specific cognitive phases to map transient network activations. Current limitations—including hardware constraints, signal artifacts, and inconsistent preprocessing pipelines—are critically analyzed. Future directions emphasize adaptive algorithms for neural state prediction, phase-specific stimulation protocols, and standardized methodologies to enhance reproducibility. By bridging mechanistic insights with personalized neuromodulation strategies, state-dependent TMS-EEG holds promise for advancing both basic neuroscience and precision medicine, particularly in psychiatric and neurological disorders characterized by dynamic neural dysregulation. Full article

Background: Lipedema is a chronic disease of subcutaneous adipose tissue that predominantly affects women and is frequently associated with endocrinopathies such as insulin resistance and obesity. Its pathogenesis is still unclear, and treatment, which requires a multi-disciplinary approach, is prolonged over time and is not always effective. There is currently no drug treatment available for this disease. Methods: Five different cases of women with lipedema and insulin resistance, treated with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and once-weekly exenatide, in association or not with lifestyle changes (diet or physical activity) for 3 to 6 months are described. Changes in anthropometric parameters, symptoms, clinical findings and the thickness of superficial adipose tissue measured by ultrasound were evaluated. Results: Treatment with exenatide, whether combined with a change in diet or physical activity, resulted in a reduction in the characteristic symptoms of lipedema, in pain evoked by pinching the adipose tissue fold and in the thickness of subcutaneous adipose tissue at the levels of the lower limbs, abdomen and upper limbs. In four out of five cases, a reduction in body weight was observed, particularly during the first three months of treatment and in cases with greater metabolic impairment. Clinical, instrumental and subjective improvements were also observed in cases where there was no reduction in body weight and in patients who had previously undergone lower limb liposuction. Conclusions: The improvement in symptoms and clinical signs of lipedema, in addition to the reduction in adipose tissue in patients with lipedema and insulin resistance with exenatide, suggests a novel pharmacological approach to the disease, which can be combined with other conservative and surgical treatments to promote weight reduction. These results also highlight the association of this disease with metabolic alterations and the fundamental role of an accurate diagnosis followed by the treatment of comorbidities and excess weight in these patients. Full article

Humor is widely recognized for its positive effects on well-being, including stress reduction, mood enhancement, and cognitive benefits. Yet, the lack of reliable tools to objectively quantify amusement—particularly its temporal dynamics—has limited progress in this area. Existing measures often rely on self-report or coarse summary ratings, providing little insight into how amusement unfolds over time. To address this gap, we developed a Random Forest model to predict the intensity of amusement evoked by humorous video clips, based on participants’ facial expressions—particularly the co-activation of Facial Action Units 6 and 12 (“% Smile”)—and video features such as motion, saliency, and topic. Our results show that exposure to humorous content significantly increases “% Smile”, with amusement peaking toward the end of videos. Importantly, we observed emotional carry-over effects, suggesting that consecutive humorous stimuli can sustain or amplify positive emotional responses. Even when trained solely on humorous content, the model reliably predicted amusement intensity, underscoring the robustness of our approach. Overall, this study provides a novel, objective method to track amusement on a fine temporal scale, advancing the measurement of nonverbal emotional expression. These findings may inform the design of emotion-aware applications and humor-based therapeutic interventions to promote well-being and emotional health. Full article

Objective: Given the side effects and reduced efficacy of conventional local anesthetics in inflammatory conditions, there is a compelling need for complementary alternative medicine (CAM), particularly those based on phytochemicals. While a previous study showed that in vivo local injection of (-)-epigallocatechin-3-gallate (EGCG) into the peripheral receptive field suppresses the excitability of rat trigeminal ganglion (TG) neurons in the absence of inflammation, the acute effects of EGCG in vivo, especially on TG neurons under inflammatory conditions, are still unknown. We aimed to determine if acute local EGCG administration into inflamed tissue effectively attenuates the excitability of nociceptive TG neurons evoked by mechanical stimulation. Methods: The escape reflex threshold was measured to assess hyperalgesia caused by complete Freund’s adjuvant (CFA)-induced inflammation. To assess neuronal activity, extracellular single-unit recordings were performed on TG neurons in anesthetized CFA-inflamed rats in response to orofacial mechanical stimulation. Results: The mechanical escape threshold was significantly lower in CFA-inflamed rats compared to before CFA injection. EGCG (1–10 mM) reversibly and dose-dependently inhibited the mean firing frequency of TG neurons evoked by both non-noxious and noxious mechanical stimuli (p < 0.05). For comparison, 1% lidocaine (37 mM), a local anesthetic, also caused reversible inhibition of the mean firing frequency in inflamed TG neurons responding to mechanical stimuli. Importantly, 10 mM EGCG produced a significantly greater magnitude of inhibition on TG neuronal discharge frequency than 1% lidocaine (noxious, lidocaine vs. EGCG, 19.7 ± 3.3% vs. 42.3 ± 3.4%, p < 0.05). Conclusions: Local injection of EGCG into inflamed tissue effectively suppresses the excitability of nociceptive primary sensory TG neurons, as indicated by these findings. Significantly, locally administered EGCG exerted a more potent local analgesic action compared to conventional voltage-gated sodium channel blockers. This heightened efficacy originates from EGCG’s ability to inhibit both generator potentials and action potentials directly at nociceptive primary nerve terminals. As a result, EGCG stands out as a compelling candidate for novel analgesic development, holding particular relevance for CAM strategies. Full article

In recent years, the application of virtual reality (VR) for spatial evaluation has gained traction in the fields of architecture and interior design. However, for VR to serve as a viable substitute for real-world environments, it is essential that experiences within VR elicit emotional responses comparable to those evoked by actual spaces. Despite this prerequisite, there remains a paucity of studies that objectively compare and evaluate the emotional responses elicited by VR and real-world environments. Consequently, it is not yet fully understood whether VR can reliably replicate the emotional experiences induced by physical spaces. This study aims to investigate the influence of presentation modality on emotional responses by comparing a VR space and a real-world space with identical designs. The comparison was conducted using both subjective evaluations (Semantic Differential method) and physiological indices (electroencephalography and heart rate variability). The results indicated that the real-world environment was associated with impressions of comfort and preference, whereas the VR environment evoked impressions characterized by heightened arousal. Additionally, elevated beta wave activity and increased beta/alpha ratios were observed in the VR condition, suggesting a state of high arousal, as further supported by positioning on the Emotion Map. Moreover, analysis of pNN50 revealed a transient increase in parasympathetic nervous activity during the VR experience. This study is positioned as a pilot investigation to explore physiological and emotional differences between VR and real spaces. Full article

Increasing evidence reveals that the deregulation of cellular antioxidant response with advancing age, resulting in the continuing amplification of oxidative stress-induced inflammatory response, is a pre-eminent cause for the onset of aging-related disease states, including blinding diseases. However, several safeguards, like an antioxidant defense system, are genetically in place to maintain redox homeostasis. Nonetheless, if the homeostatic capacity of such systems fails (like in aging), an inflammatory pathway elicited by excessive oxidative stress-evoked aberrant NLRP3 (NOD, LRR- and pyrin domain-containing protein 3) inflammasome activation can become pathogenic and lead to disease states. Among all known inflammasomes, NLRP3 is the most studied and acts as an intracellular sensor to detect danger(s). Upon activation, NLRP3 recruits apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization and facilitates the recruitment of activated Caspase-1 (Cas-1), which results in the release of inflammatory cytokines, IL-1β and IL-18 and the activation of GasderminD, an executor of pyroptosis. NLRP3 inflammasome is tightly regulated in favor of cell health. However, when and how the activation of NLRP3 and its inflammatory components goes awry, leading to cellular derangement, and what regulatory factors are involved in the normal physiological and aging/oxidative conditions will be included in this review. Also, we address the latest findings to highlight the connection between oxidative stress, antioxidants, and NLRP3 activation as this begets aging diseases and explore the cellular pathways that are in place to regulate oxidative-induced inflammations and the pathobiological consequences of dysregulated inflammatory responses and vice versa. Full article

Neurophysiological techniques, particularly somatosensory evoked potentials (SEPs) and electroencephalography (EEG), are essential tools for the functional and prognostic evaluation of patients with prolonged disorders of consciousness (DoC) in intensive neurorehabilitation settings. This narrative review critically analyzes the most relevant evidence regarding the use of SEPs and EEG in the management of post-comatose patients, highlighting the strategic role of physiatrists in integrating these assessments into individualized rehabilitation plans. A systematic search was conducted across major international databases (PubMed, Embase, Scopus, Cinahl, and DiTA) until December 2024, selecting consensus documents, official guidelines (including the 2021 ERC/ESICM guidelines), systematic reviews, observational studies, and significant Italian neurophysiological contributions. The literature supports the strong prognostic value of the bilateral presence of the N20 component in SEPs, while its early bilateral absence, particularly in post-anoxic cases, is a robust predictor of poor neurological outcomes. EEG provides complementary information, with continuous, reactive, and symmetrical patterns associated with favorable outcomes, while pathological patterns, such as burst suppression or isoelectric activity, predict a worse prognosis. Combining SEP and EEG assessments significantly improves prognostic sensitivity and specificity, especially in sedated or metabolically compromised patients. Additionally, the use of direct muscle stimulation (DMS) and nerve conduction studies enables accurate differentiation between central and peripheral impairments, which is crucial for effective rehabilitation planning. Overall, SEPs and EEG should be systematically incorporated into the evaluation and follow-up of DoC patients, and the acquisition of neurophysiological competencies by physiatrists represents a strategic priority for modern, effective, and personalized neurorehabilitation. Full article