Traumatic brain injury (TBI) represents a significant global health challenge with limited effective treatments. The secondary injury phase, characterized by persistent neuroinflammation, is a major contributor to long-term neurological deficits. Conventional therapies face substantial hurdles, including the blood-brain barrier (BBB), short therapeutic windows, and poor neuroregenerative capacity. Innovative biomaterials offer a promising platform to overcome these limitations by providing localized Drug Deliv., immunomodulation, and structural support for neural regeneration. This review outlines the pathological mechanisms of neuroinflammation and repair obstacles following TBI. It then systematically categorizes and discusses the mechanisms of various biomaterials-including natural, synthetic, nano-scale, composite, and intelligent materials-in modulating neuroinflammation. Furthermore, we elaborate on strategies for promoting neural repair, such as constructing regenerative scaffolds, delivering therapeutic agents (e.g., neurotrophic factors, stem cells, and exosomes), and remodeling the regenerative microenvironment. Special emphasis is placed on the emerging application of exosome delivery systems. Finally, we address the challenges in clinical translation and present future perspectives on smart materials, multi-modal systems, and personalized therapies, highlighting the transformative potential of biomaterials in TBI management.

Glioblastomas represent the most aggressive and lethal form of primary brain cancer and continue to pose a major challenge to global health. MicroRNAs (miRNAs), as central regulators of gene expression, are intimately involved in the initiation, progression, and therapeutic resistance of numerous malignancies, including glioblastoma. Therefore, this class of non-coding RNAs are considered to be valuable candidates for innovative therapeutic strategies. However, despite many promising preclinical studies, miRNA-based therapies have yet to be translated into routine clinical practice. In the context of glioblastoma, one of the principal obstacles to the effective delivery of synthetic miRNA therapy is their limited ability to cross the blood-brain barrier (BBB). To address this challenge, a variety of locoregional delivery strategies have been developed in recent years. In this review, we provide a detailed discussion and a state-of-the-art overview of these local delivery methods in the context of glioblastoma treatment, with a specific emphasis on their application for delivering miRNA-based therapeutic oligonucleotides, formulated either with or without synthetic nanoparticles.

Mushroom use dates back to ancient times, and it currently remains significant among indigenous and urban populations as a medicinal option. Psilocybe species are suggested to modify emotions when administered in macro- or microdose form for the treatment of anxiety and depression, both often affected by a delayed onset and adverse effects of current pharmacological therapy. The objective of this study was to evaluate the anxiolytic and/or antidepressant-like effects of P. cubensis mushroom aqueous extract (PcAE) microdosing in mice using open-field and rota-rod tests, followed by plus-maze or forced swimming tests. We also evaluated changes in neuronal activity and dendritic maturation using electrocorticography (ECoG) and immunohistochemical techniques. The outcomes were compared with an effective macrodose of PcAE and antidepressant fluoxetine (FLX). For this study, mice were grouped as follows: (1) vehicle, (2) acute, and (3) repeated (10 days) PcAE microdosing (1 µg/kg); (4) single PcAE macrodose (1 g/kg); and (5) acute and (6) repeated reference drug fluoxetine (FLX, 10 mg/kg).The anxiolytic and antidepressant-like effects using microdosing were similar to those observed with macrodoses of PcAE and FLX; significant dose- and/or time-dependent changes in the ECoG and dendritic maturation of hippocampus neurons were also observed, in addition to altered corticosterone levels. To conclude, P. cubensis mushroom promotes brain effects in mice after micro- and macrodosing, supporting its potential as a therapeutic alternative for mental health.

Oxidative stress is intrinsically linked to mental disorders, involving an imbalance between reactive species and antioxidant defenses, where catalase is an essential, ubiquitous antioxidant enzyme. The pleiotropic effects of antipsychotic drugs, used for schizophrenia and mood disorders, are not fully elucidated at the molecular level. This study characterized the binding of a highly effective but potentially dangerous antipsychotic, clozapine (CLZ), to commercial bovine liver catalase (BLC). Using various spectroscopic methods under simulated physiological conditions, we found a moderate binding affinity of CLZ for BLC (K_a = 1.4 × 10^-5 M^-1), subtly influencing the protein's secondary and tertiary structures and slightly increasing its thermal stability. CLZ efficiently protected BLC against free-radical-induced oxidation and preserved its catalytic activity for decomposing toxic hydrogen peroxide. The effect of CLZ on BLC antioxidant activity was dual: no significant effect at lower, physiologically relevant concentrations, but significant inhibition at saturating, toxic drug concentrations. Molecular docking and molecular dynamics results indicated the presence of two specific binding sites within BLC monomers, one located near its active site. In conclusion, our in vitro results indicate that CLZ's specific binding to BLC can be both beneficial and potentially harmful, and that this effect is dose-dependent.

Neuropsychiatric and neurodegenerative disorders impose a substantial global health burden, yet progress in mechanism-based therapy remains limited by clinical heterogeneity and an incomplete understanding of disease biology. Emerging evidence implicates ferroptosis-an iron-dependent form of lipid peroxidation-driven cell death-as a shared pathogenic process across primary psychiatric disorders and neurodegenerative diseases with prominent neuropsychiatric features. In this review, we synthesize evidence from major depressive disorder, schizophrenia, substance use disorders, Alzheimer's disease (AD), and Parkinson's disease (PD), highlighting ferroptosis as a common mechanism linking iron dyshomeostasis to neuronal dysfunction. Mechanistically, ferroptosis is organized around three interconnected modules: amino acid metabolism, lipid peroxidation, and iron handling. These pathways converge on mitochondrial dysfunction, oxidative damage, and neuroinflammatory amplification. We further propose that each disorder displays a distinct ferroptosis signature, including dopamine quinone-mediated GPX4 loss in PD, AICD-dependent transcriptional reprogramming in AD, and inflammatory-glutamatergic lowering of the ferroptotic threshold in depression and schizophrenia. Together, these insights position ferroptosis as a candidate framework for biomarker development, patient stratification, and mechanism-informed therapeutic intervention across neuropsychiatric disease.

Background and Objectives: Low back pain (LBP) is a leading cause of disability worldwide and is frequently associated with intervertebral disc degeneration (IVDD). Current therapeutic strategies are primarily symptomatic and do not restore native disc biology, largely due to the avascular nature of the intervertebral disc and the hostile inflammatory and mechanical microenvironment that characterizes degeneration. The aim of this study is to provide an updated and clinically oriented overview of the pathophysiology of IVDD and to evaluate the current evidence on mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP)-based therapies. Materials and Methods: A focused narrative literature review was performed to evaluate current evidence on MSC- and PRP-based therapies for intervertebral disc degeneration (IVDD). The search was conducted in PubMed. Only studies in English were considered eligible. Results: Mesenchymal stem cells (MSCs) demonstrated regenerative and immunomodulatory effects primarily through paracrine mechanisms, enhancing extracellular matrix synthesis and reducing inflammation and apoptosis. MSC-derived extracellular vesicles emerged as a promising cell-free alternative, potentially overcoming limitations related to cell survival and safety. Platelet-rich plasma (PRP) showed anabolic and anti-inflammatory properties, promoting disc cell proliferation and matrix production, particularly in early-stage degeneration. Clinical studies, including randomized trials, reported significant improvements in pain and function for both MSC and PRP therapies, with favourable safety profiles. However, heterogeneity in treatment protocols and limited long-term data remain significant limitations. Orthobiologic therapies represent a minimally invasive option for patients with discogenic low back pain refractory to conservative treatment. Patient selection is crucial and should consider degeneration stage, disc viability, and clinical presentation. PRP is primarily indicated in early-stage degeneration (Pfirrmann II-III), whereas MSC-based therapies may be considered in selected patients with more advanced but still viable discs. Based on current evidence, a stepwise approach is proposed, progressing from conservative management to PRP, MSCs, and ultimately surgery. Orthobiologics should be integrated within a multimodal strategy including rehabilitation. Conclusions: MSCs and PRP represent a promising and, eventually, complementary orthobiologic therapies for IVDD. PRP is primarily effective in early degenerative stages as a biologic stimulator, whereas MSCs may provide regenerative benefits in more advanced but still viable discs. Further studies are necessary to standardize protocols and confirm long-term efficacy and safety.

Background and objectives: Ischemic priapism is a rare but serious adverse effect of trazodone, associated with a high risk of long-term sexual dysfunction. While its urological consequences are well described, psychiatric and psychosocial outcomes remain insufficiently explored. This study assessed psychiatric and sexual sequelae following trazodone-associated ischemic priapism and compared clinical characteristics with trazodone-treated patients without priapism. Materials and Methods: In this single-center observational study, 268 adult patients receiving trazodone were analyzed, including 17 patients with ischemic priapism and 251 controls. Data on episode duration and urological management were collected. Psychiatric status and sexual functioning were evaluated through structured clinician-led interviews informed by validated psychometric frameworks during hospitalization and at 1-, 3-, and 6-month follow-up. Nonparametric analyses and Spearman rank correlations were applied. Results: Patients with priapism were significantly older than controls (44.1 ± 5.1 vs. 39.0 ± 4.4 years; p < 0.0001), while trazodone dose distribution did not differ between groups. The mean episode duration was 26.5 ± 16 h (median 24 h). Older age and longer ischemic duration were independently associated with increased treatment intensity, whereas trazodone dose was not. Persistent depressive and anxiety symptoms and impaired sexual functioning were observed in a subset of patients during follow-up. Conclusions: Trazodone-associated ischemic priapism is not only an acute urological emergency but may also lead to sustained psychiatric and sexual sequelae. Interdisciplinary follow-up should be considered to address long-term psychosocial outcomes.

Toxoplasma gondii establishes latent infection in a substantial proportion of the global population, yet the long-term health consequences of this infection remain incompletely characterized. We conducted a retrospective observational matched cohort study using longitudinal electronic health record data from a nationwide integrated healthcare provider, including members aged 18-45 years who underwent routine Toxoplasma serologic screening, typically performed in obstetric evaluation, excluding patients with clinical toxoplasmosis, immunosuppression, or HIV. Seropositive individuals were matched 1:1 without replacement to seronegative controls to align demographic, temporal, and socioeconomic variables. Time-to-event associations with predefined medical conditions were evaluated using Cox proportional hazards models with false discovery rate correction. The final cohort included 19,443 seropositive individuals and 19,443 matched controls (96.7% female), with a tight baseline balance of demographic and temporal characteristics. During follow-up, seropositivity was associated with increased risks of tobacco dependence (aHR 1.65), alcohol dependence (2.32), suicide attempt (1.82), motor vehicle accidents (1.22), and work accidents (1.27), as well as multiple infectious conditions, including hepatitis B (1.55), hepatitis C (2.15), and syphilis (2.43), with an overall trend toward increased all-cause mortality (1.32, 95% CI [1.00-1.74]). These findings suggest that asymptomatic Toxoplasma infection in young adults is associated with increased long-term behavioral and medical comorbidity.

Background: The prevalence of neurodegenerative diseases like Alzheimer's and mental disorders like depression or anxiety appears higher in patients with gastrointestinal tract diseases like inflammatory bowel disease (IBD). Conversely, depressed patients have higher rates of gastrointestinal disorders. These observations suggest bidirectional communication between the brain and the gastrointestinal tract, the so-called "gut-brain axis". Moreover, an altered microbiota, called "dysbiosis", has been reported in these diseases, highlighting the network between gut microbes and their host. The emergence of the microbiota as a key regulator of the gut-brain dialog has led to the establishment of the concept of the "microbiota-gut-brain axis". Objectives: In this narrative review, we outline the main interaction channels between the gastrointestinal tract and the brain. Then, we summarize current knowledge of two major diets (i.e., Western and Mediterranean diets) and the principal dietary components that modulate the microbiota-gut-brain axis to discuss the mechanisms putatively involved in intestinal, psychiatric, and neurological disorders. Conclusions: Diet is a major factor influencing the gut microbiota, and consequently, also putatively systemic mechanisms through the microbiota-gut-brain axis. Indeed, the composition of the diet is crucial for health and disease. Despite the main role of diet, the physiological, cellular, or molecular mechanisms involved in the complex communication between the microbiome, gut, and brain are still poorly understood.

Background/Objectives: Psychological pain-also termed psychache or mental pain-has been suggested to constitute a relevant factor in the emergence of suicidal behaviour. Despite conceptual advances, empirical research on interventions specifically designed to alleviate psychological pain in individuals who have attempted suicide remains scarce. The present scoping review maps existing psychological and pharmacological interventions targeting psychological pain, identifies their core components, delineates gaps for future research, and proposes a therapeutic intervention protocol. Methods: Literature was searched through PubMed, PsycInfo, and ClinicalTrials.gov (until October 2025) using combinations of the terms suicide, psychache, psychological pain, intervention, treatment, therapy, pharmacological treatment, and psychotherapy. Both randomised controlled trials, non-randomised controlled trials, and literature reviews were included. Results: Evidence indicates that few interventions explicitly target psychological pain. Most suicide-specific therapies indirectly address components of psychological pain-such as unbearable affect, loss of meaning, and social disconnection. Narrative-based, emotion regulation, and acceptance-based therapies appear promising. Emerging pharmacological approaches may relieve psychological pain; however, further evidence is required. Conclusions: Integrating psychological pain as a therapeutic focus-through narrative, tolerance-building, and relational strategies-may enhance post-attempt interventions. Future trials should systematically measure psychological pain and test its role as a mediator of suicidal outcomes.