Search Results (1,569)

Background/Objectives: Metastatic prostate cancer is increasing in the Gulf Cooperation Council countries. This study presents a multimodal treatment protocol incorporating radiotherapy to primary and metastatic sites, guided by PSMA PET/CT, combined with systemic therapy for non-metastatic pelvic node-positive and de novo low-volume metastatic prostate cancer. Methods: We conducted a retrospective cohort study of patients treated with radical radiotherapy doses (68 Gy/25 Fr or 78 Gy/39 Fr) to the prostate gland and gross pelvic disease, and SBRT (35–40 Gy/5 Fr) to distant bone metastases. All patients received LHRH agonists ± abiraterone/prednisone or enzalutamide. Results: Twenty-four consecutive patients were analyzed. The median age was 70.1 years (IQR, 65.7–77.7), the median baseline PSA was 27.9 ng/mL (IQR = 19.7–53.8), and median follow up was 24 months (IQR = 20.4–31.2). Clinical staging was cT3b in (46%), cT2 in (25%), cT4 in (17%), cT3a in (13%) of patients. Pelvic nodal involvement (cN1) was present in 91.7% of patients, while 54.1% had metastatic disease. Treatment was well tolerated. Acute toxicity was predominantly grade 1 genitourinary (GU) toxicity, occurring in 87.5% of patients, with grade 2 GU toxicity observed in 8.2% and no acute gastrointestinal (GI) toxicity. Late toxicity remained minimal, with grade 1 and grade 2 GU toxicity reported in 45.8% and 4.2% of patients, respectively, and no late GI toxicity. Mild systemic treatment-related toxicities were reported in 25% of patients, including sexual dysfunction, hypokalemia, muscle weakness, osteoporosis and depression/anxiety. At the six-month follow-up PSMA PET/CT assessment, 85.7% achieved a complete metabolic response, and 14.2% achieved a partial response. Biochemically, 75% of patients achieved undetectable PSA levels (<0.01 ng/mL), with all patients achieving a PSA nadir < 0.2 ng/mL. Conclusions: This first, hypothesis-generating real-world experience from the GCC, suggests that an integrated approach combining systemic therapy with metastasis-directed therapy is feasible. Prospective randomized studies are required to validate these results. Full article

Background: Spinal cord injury (SCI) triggers secondary injury processes involving neuroinflammation and systemic immune remodeling. The endocannabinoid system (ECS) has been implicated in neuroimmune regulation, but its transcriptional relationship with immune remodeling and its translational relevance in human SCI blood remain incompletely defined. Methods: A cross-species discovery–validation–translation framework was applied using a rat spinal cord discovery cohort (GSE45006), an independent mouse validation cohort (GSE171441), and a human peripheral white blood cell cohort (GSE151371). Analyses included differential expression profiling, ECS-focused assessment, cross-species comparison, immune-cell signature scoring, ECS–immune correlation analysis, receiver operating characteristic (ROC) analysis, LASSO-based biomarker prioritization, network analysis, disease enrichment, drug–gene interaction querying, and transcription factor/microRNA regulatory annotation. Results: ECS-related transcriptional remodeling was identified across rodent and human datasets in a compartment-dependent manner. In human SCI blood, CNR2, PTGS2, and DAGLB were significantly altered and showed biomarker-prioritization potential. Human SCI blood also showed innate immune enrichment, adaptive immune depletion, and significant ECS–immune correlations. The integrated 28-gene SCI–ECS immune panel formed a functionally coherent protein–protein interaction (PPI) network enriched in immune-response pathways. Disease enrichment supported an immune/inflammatory pathological context, whereas DGIdb identified hypothesis-generating drug–gene relationships involving ECS-related targets. ChEA 2022 revealed nominal transcription factor annotations that did not survive multiple-testing correction, and miRNet identified database-derived miRNA regulators of panel genes. In a secondary sensitivity analysis, the combined ECS signature also retained discriminatory performance against non-CNS trauma controls, suggesting that the observed transcriptional pattern was not fully attributable to generalized trauma-related responses. Conclusions: This study proposes an ECS-associated immune remodeling signature in SCI with translational biomarker-prioritization and pharmacologic target-annotation context in human peripheral blood. These findings are exploratory and require prospective and functional validation. Full article

Vitamin D has long been recognized for its role in calcium homeostasis and bone metabolism; however, it is now emerging as an important regulator of central nervous system (CNS) function. Recent evidence suggests that vitamin D signaling contributes to the pathogenesis and progression of several neurodegenerative disorders. Vitamin D exerts neuroprotective effects through multiple mechanisms, including regulation of calcium homeostasis, modulation of immune responses, reduction in oxidative stress, stimulation of neurotrophic factors, and maintenance of blood–brain barrier (BBB) integrity. Vitamin D receptors and metabolizing enzymes are widely distributed across several brain regions, highlighting their direct involvement in neuronal function. This review summarizes the biosynthesis, metabolism, and signaling pathways of vitamin D. It explores its role in neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury (TBI). Evidence from experimental and clinical studies indicates that vitamin D deficiency is associated with an increased risk and severity of these conditions, while supplementation may provide therapeutic benefits. Full article

Background/Objectives: Absent septum pellucidum (ASP) is a rare fetal midline brain finding that may occur in isolation or alongside broader central nervous system (CNS) malformations, genetic disorders, or septo-optic dysplasia (SOD). Accurate prenatal diagnosis and counseling remain challenging because apparently isolated ASP may be reclassified following fetal magnetic resonance imaging (MRI), postnatal neuroimaging, or specialist assessment. This structured narrative review aimed to synthesize current evidence on prenatal imaging findings, associated anomalies, genetic evaluation, and postnatal outcomes in fetuses with ASP. Methods: This structured narrative review used PRISMA-informed reporting. PubMed and Google Scholar were searched for full-text English-language studies published from 2014 through the updated search date (8 June 2026). Data on gestational age at diagnosis, imaging classification, associated anomalies, genetic testing, postnatal assessment, and neurodevelopmental, ophthalmological, and endocrine outcomes were extracted. Study methodological quality was appraised using Joanna Briggs Institute tools. Results: Seven studies comprising 342 fetal ASP cases were included. Of these, 94 cases (27.5%) were classified as isolated ASP prenatally, but only 57 remained isolated postnatally when follow-up data were available. SOD was confirmed after birth in 11 of 94 (11.7%) fetuses with prenatally isolated ASP. As definitions, imaging protocols, genetic testing strategies, and follow-up duration differed substantially across studies, these pooled values are descriptive observations rather than formal quantitative estimates. Conclusions: ASP is a heterogeneous prenatal finding. The prognosis is most favorable when ASP remains isolated following a detailed prenatal and postnatal evaluation. Multidisciplinary follow-up involving fetal medicine, neuroradiology, genetics, ophthalmology, endocrinology, and neurology is essential for risk stratification and counseling. Full article

Hypoxia is a prevalent characteristic of neurological diseases, including ischemic injury, neurodegeneration and infectious disease complications. Concurrently, hypoxia shapes both protective and pathological responses within the central nervous system (CNS). Central to this process is hypoxia-inducible factor 1α (HIF1α), a transcription factor that regulates cellular adaptation to reduced oxygen availability through coordinated glycolytic, inflammatory and cell survival pathways. Under hypoxic conditions, HIF1α transcriptional activity influences microglial activation, mitochondrial quality control, and cytokine production, thereby modulating neuroinflammation and neuroprotection. Preclinical evidence points toward hypoxia preconditioning being neuroprotective through HIF1α-dependent mechanisms in a context-dependent matter. This review synthesizes the current understanding of the role of HIF1α across neurological disease contexts, highlighting the intersection of hypoxia, neuroinflammation and neuronal survival. Ultimately, defining the cell-specific and context-dependent involvement of HIF1α will be critical for targeted therapeutic approaches to alleviate neuronal death and slow disease progression. Full article

Neuroinflammation is a key hallmark of both neurodegenerative and neurospecific autoimmune diseases, including multiple sclerosis (MS), where immune dysregulation contributes to cellular stress, autophagy, and disease progression in Alzheimer’s disease (AD), Parkinson’s disease (PD), and MS. Emerging evidence suggests a shared mechanism behind MS, AD, and PD, driven by chronic interaction between the peripheral immune system and the central nervous system (CNS). While MS was traditionally viewed as a primary autoimmune condition, recent research indicated that all three disorders involve a breakdown of the blood–brain barrier (BBB). This structural failure enables peripheral immune cells and cytokines to enter the brain, causing sustained neuroinflammation and accelerating disease progression. Here, we propose an end-to-end framework for identification of the diagnostic and therapeutic cell-specific protein markers commonly regulated in mild–moderate AD (MMAD), early-stage PD (ESPD), and MS within peripheral blood mononuclear cells (PBMCs). PBMC markers were first identified based on shared differential protein expression, followed by filtering for BBB permeability. Subsequently, sorted cell markers were mapped to disease-specific neural cell types. Our analysis suggests that PBMC-derived cells, including astrocyte- and monocyte-like populations, share overlapping transcriptional signatures and functional similarity with macrophages and neuroglial cells, indicating potential transcriptional similarity or functional convergence. Furthermore, intra- and inter-cellular pathway analysis suggested both shared and disease-specific signaling mechanisms, with kinase–integrin interactions emerging as key regulatory factors. Selected potential seed markers, primarily kinases and immunoglobulins, were further analyzed through evolutionary sequence–structure space to identify druggable structural features. Next, protein moonlighting possibilities were tested to enhance the temporal functional trajectory of the markers for precise therapeutic impact. Hence, the framework provides a robust strategy to identify immune-based disease-specificcandidate diagnostic andpotential therapeutic targets. Full article

Multiple sclerosis (MS) is a neuro-inflammatory disease characterized by demyelination in the central nervous system (CNS). Although a substantial endogenous capacity for remyelination has been demonstrated, this process is frequently incomplete and exhibits marked intra- and inter-individual heterogeneity. Several factors influence the extent of spontaneous myelin regeneration, including age, sex, disease course, and lesion localization. Oligodendrocytes (OL), derived from oligodendrocyte progenitor cells (OPCs), are the principal myelinating cells of the CNS. The regenerative cascade involves several key stages, including OPC activation, recruitment, differentiation into oligodendrocytes (OL), and myelin deposition. This process is orchestrated in a spatiotemporal manner by a complex interplay of intracellular signaling pathways, genetic determinants, and dynamic microenvironmental cues, which together balance inhibitory and pro-remyelinating influences. Several lines of evidence indicate that chronically demyelinated axons are vulnerable to degeneration, whereas successful remyelination may confer neuroprotection. These observations underscore remyelination as a promising neuroprotective therapeutic target for preventing or slowing disability progression in MS, a condition in which gradual neuroaxonal degeneration is believed to underlie irreversible disability progression. In this review, we aim to bridge the gap between fundamental biological mechanisms of remyelination and their clinical relevance. We examine recent advances in in vivo techniques for assessing remyelination and discuss how these measures correlate with clinical and disability outcomes. In addition, we review recent clinical trials of remyelination-promoting therapies and analyze the challenges that have limited their advancement beyond phase II. Overall, we seek to provide a comprehensive overview of the remyelination process from bench to bedside, highlighting both the obstacles and the therapeutic potential of remyelination strategies in MS. Full article

Cancer-related cognitive impairment (CRCI), also known as chemobrain or chemofog, is characterized by subjective and/or objective changes in attention, executive functions, memory, and processing speed in patients with non-CNS cancers, particularly women with breast cancer. This structured narrative review synthesizes current evidence on mechanisms, neuropsychological assessment, neuroimaging correlates, clinical and demographic risk factors, emerging artificial intelligence and machine learning applications, and non-pharmacological approaches to CRCI in breast cancer. A structured literature search was conducted using PubMed/MEDLINE, PsycInfo, and Clinical Key up to May 2026, with emphasis on studies published between 2023 and 2026. Peer-reviewed English-language studies involving adult breast cancer populations and addressing predefined thematic domains of CRCI were considered. Given the heterogeneity of study designs, assessment tools, interventions, and outcomes, the findings were synthesized narratively. Current evidence supports a multifactorial model of CRCI involving neurobiological, treatment-related, psychological, and behavioral mechanisms. Neuroinflammation, endocrine disruption, oxidative stress, glial alterations, and structural or functional brain changes may contribute to cognitive symptoms; however, the strength of evidence varies, and many findings remain correlational or preclinical. Non-pharmacological interventions, including cognitive training, physical activity, mindfulness-based and psychological approaches, and multimodal digital programs, appear promising as supportive strategies. However, evidence remains heterogeneous, with benefits more consistently reported for patient-reported outcomes, fatigue, emotional distress, and quality of life than for objective neuropsychological performance. CRCI in breast cancer should be approached as a heterogeneous condition requiring early recognition, standardized assessment, and multidisciplinary supportive care. Future research should prioritize longitudinal designs, harmonized endpoints, and a clearer distinction between subjective and objective outcomes. Full article

JAZ (Jasmonate ZIM-Domain) proteins are key negative regulators of the jasmonic acid (JA) signaling pathway and are involved in various plant growth, development, and stress regulation. However, the functions of the JAZ gene family in Camellia nitidissima remain poorly understood. Here, ten CnJAZ genes were identified at the genome-wide level, encoding 134–398 amino acids and unevenly distributed across eight chromosomes. All CnJAZs were predicted to localize to the nucleus. Based on phylogenetic and structural analyses, the ten CnJAZs were classified into five subfamilies, with members of the same subfamily sharing similar exon–intron structures. Collinearity analysis with Arabidopsis thaliana and Malus domestica suggests that the JAZ gene family shares a common ancestor. Promoter analysis revealed cis-acting elements responsive to light, methyl jasmonate (MeJA), and anaerobic stress. Transcriptome profiling showed that most CnJAZs exhibit tissue- and development-specific expression, particularly during flower development and organ formation. RT-qPCR confirmed that MeJA and gibberellin (GA₃) significantly induced the expression of CnJAZ, whereas ethylene (ETH) treatment up-regulated CnJAZ3 and CnJAZ5 by 80-fold after three hours. These findings highlight their important roles in growth, development, and hormonal regulation in C. nitidissima, laying a foundation for functional studies. Full article

The axis linking the gut to the brain to the immune system connects all tissues involved—bacteria, immune cells, metabolism and the CNS—through a multidirectional communication network. Several studies have confirmed that when this axis is disrupted, it can be responsible for Alzheimer’s disease, Parkinson’s disease, obesity, type 2 diabetes, and NAFLD, and the main consequences come from increased systemic inflammation, altered regulation of immune cells, the production of microbial metabolites that alter signals to the immune cells and nervous system, increase in oxidative stress, breakdown of the gut barrier, and more. In recent years, advanced multi-omics technologies, such as metagenomics, transcriptomics, metabolomics, proteomics, and single-cell sequencing, have provided significant advancement in our understanding of all of the interacting nodes involved in the gut–brain–immune axis. These advanced sequencing technologies can characterize the microbial communities, host immune cells, metabolic profiles, and the degree of cell heterogeneity during a specific disease. Combining multi-omics information can reveal a few shared pathways between neurodegenerative and metabolic disorders, such as NF-κB, NLRP3 inflammasome activation, mitochondrial dysfunction, changes in SCFA metabolism, and the alteration of microbial populations in Alzheimer’s and Parkinson’s disease; metabolic dysbiosis and increased risk for Parkinson’s disease; or changes in gut-to-brain-to-immune signaling contributing to diabetes complications and NAFLD. Artificial intelligence (AI) and machine learning are becoming promising tools for detecting biomarkers from these datasets, extracting knowledge, interpreting systems biology, and helping with developing precision medicine. In this review, we summarize current evidence that supports the role of the gut–brain–immune axis in neurodegenerative and metabolic diseases, highlighting results gained with the utilization of multi-omics approaches. We will describe the key microbial, immune, and metabolic pathways involved in pathogenesis and therapeutic approaches including psychobiotics, tailored nutrition, modulation of the microbiome, and metabolite interventions, discussing future perspectives of the translation of the gut–brain–immune axis knowledge into clinical practice. Full article

Background: Multiple sclerosis (MS), an autoimmune disease, involves peripheral immune activation followed by CNS inflammation in a compartmentalized manner. Although high-efficacy disease-modifying therapies (HE-DMTs) have been effective in suppressing relapses in MS patients, they fail to effectively target chronic microglial activation and smoldering lesions in MS patients. Bruton’s tyrosine kinase inhibitors (BTKis), which are orally active and capable of crossing the blood–brain barrier, have been found to be effective in modulating B cells and CNS-resident myeloid cells. Objective: The objective was to assess the efficacy and safety of Bruton’s tyrosine kinase inhibitors in patients with relapsing, secondary, and primary progressive MS. Methods: We performed a systematic review and meta-analysis according to the Cochrane and PRISMA guidelines (PROSPERO registration number: 1323474). We included randomized controlled trials (RCTs) that assessed fenebrutinib, evobrutinib, or tolebrutinib in adult MS patient populations. The main outcome measures were annualized relapse rate, MRI lesion activity, disability progression (EDSS), and hepatotoxicity. The quality of the included trials was assessed for bias by the RoB2 tool. Results: Six RCTs with 3616 participants were included. BTK inhibitors significantly reduced ARR compared with control therapy (pooled RR 0.24; 95% CI 0.15–0.39). MRI activity was reduced (mean difference −1.45 new/enlarging T2 lesions; 95% CI −2.08 to −0.82). Disability progression was unchanged in short-term relapsing MS trials. Serious hepatotoxicity was reported in 11.0% of BTKi-treated patients compared with 13.7% of control patients (pooled RR 0.80; 95% CI 0.66–0.96). However, increased transaminase elevations were reported in placebo-controlled trials, which indicates that hepatotoxicity remains a clinically relevant safety concern for the class. Conclusions: BTK inhibitors reduce inflammatory disease activity in relapsing MS and have emerging efficacy in progressive MS phenotypes; however, continued monitoring for hepatotoxicity is warranted. Optimization of CNS penetrance and pharmacologic selectivity may influence long-term clinical positioning. Full article

Traumatic brain injury (TBI) is a global public health problem which causes long-term neurologic damage caused by both primary mechanical injury and secondary pathological processes. Extracellular vesicles (EVs) such as exosomes, microvesicles (MVs) and apoptotic bodies (ApoBDs) serve as critical vehicles mediating intercellular communication in the central nervous system (CNS) following TBI. The biogenesis and the content of EVs, including proteins, lipids and RNAs, are greatly changed and involved in the evolution of inflammation or tissue repairing after TBI. In this overview, we recapitulate the cellular origin of EVs and the function of EVs in the neuroinflammatory process after TBI, highlighting the dual regulatory roles of EVs in the biological response to TBI, whereby certain EV populations amplify secondary injury cascades, while others promote endogenous repair and recovery processes. We next investigate the progress in EV engineering and targeted delivery systems and report the potential mechanisms, emphasize the prospects and potential of engineered EVs for therapy, and comment on challenges and perspectives for clinical application in TBI. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) and the accumulation of tau in the brain, which triggers robust innate immune responses. Growing evidence indicates that neuroinflammation contributes to AD progression by overactivating microglia through the release of cytokines and chemokines. In general, chemokines can disrupt neuronal communication and promote blood–brain barrier permeability. Peripheral immune cells are mobilized into the brain by a gradient of chemokines. These processes link peripheral immune responses with substantial T-cell infiltration into the CNS parenchyma, leptomeninges and cerebrospinal fluid of both AD mice and AD patients. This finding underscores the relevance of the adaptive immune system, particularly T and B cells, in AD neuropathology. T-cell infiltration into the brain can influence amyloid clearance through chemokine signalling. However, chemokines play a critical role in AD by either promoting or suppressing disease progression. The infiltration of peripheral T and B cells into the brain parenchyma can exacerbate neuronal loss, yet it may also exert neuroprotective effects. Despite the presence of CD4⁺ and CD8⁺ T cells in postmortem brains of AD patients, debate continues about their role in AD brains, in terms of whether they are protective or detrimental. Understanding the complex role of chemokines in controlling innate and adaptive immune responses by modulating neuron–glia interactions (involving astrocytes and microglia) may provide novel therapeutic approaches for AD. Targeting chemokine signalling or treating with drugs that can prevent the recruitment of immune cells may be promising strategies for treating AD neuropathology. Therapies that prevent the overactivation of T cells in the brain could lead to protective strategies against AD. In fact, regulatory T cells (Tregs) could delay the onset of cognitive symptoms, because they suppress inflammation and slow the accumulation of Aβ plaques and p-Tau in the brain. Complementary strategies, such as photobiomodulation, nanoparticle, and T-cell-based approaches, could mitigate AD progression in patients. Full article

Essential tremor (ET) is a common movement disorder increasingly recognized as a complex syndrome with neurodegenerative features. While mitochondrial dysfunction and cellular aging are implicated in several neurodegenerative diseases, their role in ET remains unexplored. To investigate mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) in patients with ET and evaluate their potential as biomarkers of mitochondrial dysfunction and biological aging. In this cross-sectional case–control study, 68 ET patients (median age 66 years; 64.7% male) and 62 healthy controls (median age 70 years; 54.8% male) were enrolled. Relative mtDNA-CN and TL were quantified by quantitative PCR, measuring mitochondrial ND1 gene levels and telomere-to-single-copy gene (T/S) ratio, respectively, both normalized to β-actin. Associations with disease status were assessed using age- and sex-adjusted multivariable linear regression on log₂-transformed data, with statistical significance defined as p < 0.05 after false discovery rate (FDR)-corrected Wald tests. Receiver operating characteristic (ROC) and effect size (Cohen’s d) analyses were performed. ET patients showed significantly reduced mtDNA-CN (β = −2.785, 95% CI −3.700 to −1.869; p_FDR = 2.53 × 10⁻⁹) and TL (β = −2.073, 95% CI −2.758 to −1.388; p_FDR = 3.00 × 10⁻⁹), corresponding to ~6.9-fold and ~4.2-fold reductions, respectively. Age- and sex-stratified analyses confirmed consistent reductions, more pronounced in older individuals. Both biomarkers showed good discriminatory performance (mtDNA-CN: AUC = 0.83, 95% CI: 0.75–0.90; TL: AUC = 0.76, 95% CI: 0.68–0.85) and large effect sizes (Cohen’s d = |1.192| and |1.058|), respectively. Reduced mtDNA-CN and TL support the involvement of mitochondrial impairment and accelerated cellular aging in ET and may represent accessible peripheral biomarkers and provide a basis for future longitudinal and mechanistic investigations. Full article

Mechanisms of arboviral neuroinvasion are still incompletely resolved, despite longstanding emphasis on the blood-brain barrier (BBB) as the principal interface for central nervous system (CNS) entry. While BBB-centered models have been highly informative, they may underrepresent the contribution of other CNS border structures, particularly the choroid plexus and the blood-cerebrospinal fluid barrier (BCSFB). Here, we re-examine the BCSFB as a relevant but unevenly supported neuroinvasion interface in arboviral encephalitis. The strongest direct evidence is currently available for Zika virus (ZIKV), for which experimental studies support infection of choroid plexus-associated cells and CNS access through the blood-CSF axis. Semliki Forest virus (SFV) provides additional direct, although still limited, support for this concept. In contrast, for West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV), evidence for choroid plexus involvement remains indirect or insufficiently resolved, even though neuroinvasion itself is well established. We therefore argue not for replacement of BBB-centered models, but for broader integration of the BCSFB into current frameworks of arboviral CNS invasion. This evidence-based perspective supports a hierarchical, virus-dependent view of choroid plexus involvement and highlights the need for mechanistic studies that directly test when and how this interface contributes to encephalitic disease. Full article