Search Results (9,604)

Immunotherapy has transformed cancer treatment; however, clinical benefit remains limited to a subset of patients, underscoring the need for robust biomarkers that capture tumor-immune interactions across cancer types. In this study, we performed a comprehensive pan-cancer, multi-omics characterization of the immune checkpoint–related molecules CD70, CD80, and TIGIT to evaluate their diagnostic, prognostic, and immunological relevance. Using integrative analyses of transcriptomic, epigenomic, genomic, pharmacogenomic, and single-cell RNA-sequencing data from The Cancer Genome Atlas and complementary resources, we assessed expression patterns, DNA methylation, somatic mutations, copy number alterations, immune infiltration, tumor stemness, and drug sensitivity. CD70, CD80, and TIGIT were broadly dysregulated across multiple malignancies, with coordinated overexpression particularly evident in kidney renal clear-cell carcinoma. Elevated expression of these immune checkpoints was associated with advanced tumor stage, aggressive molecular subtypes, and unfavorable survival outcomes in selected cancers, including uveal melanoma and renal malignancies. Functional analyses revealed significant associations between checkpoint expression and key oncogenic pathways, including epithelial–mesenchymal transition, apoptosis, and hormone receptor signaling, suggesting links with tumor progression and immune activation states. Immune deconvolution analyses indicated that TIGIT expression is associated with a T-cell–inflamed microenvironment and reduced neutrophil infiltration, while CD80 exhibited methylation-dependent associations with immune cell composition. Genomic and epigenetic alterations were found to correlate with checkpoint expression patterns and immune phenotypes across tumor types. Pharmacogenomic profiling identified associations between checkpoint expression and sensitivity to multiple anticancer agents; however, these findings are based on cell line datasets and should be considered predictive. Single-cell transcriptomic analyses further resolved cell-type–specific expression patterns, distinguishing tumor-intrinsic from immune-restricted expression profiles. Collectively, our findings establish CD70, CD80, and TIGIT as integrative biomarkers of tumor progression, immune contexture, and therapeutic response, providing a rationale for their clinical exploitation in precision immuno-oncology. Full article

Background: Neuropathic pain remains difficult to treat because current analgesics often provide insufficient efficacy or dose-limiting adverse effects. Nav1.7 is genetically validated as a key regulator of human pain sensation, but the development of selective small-molecule Nav1.7 inhibitors has been limited by the high similarity among voltage-gated sodium channel subtypes. Methods: We generated monoclonal antibodies selectively targeting Nav1.7, humanized them for therapeutic development, and evaluated their binding, selectivity, functional channel inhibition, systemic analgesic efficacy, and effects on neuronal activity in a rat model of partial sciatic nerve ligation-induced neuropathic pain. Results: The humanized antibodies showed high-affinity and selective binding to Nav1.7 and functionally inhibited the channel in cellular assays. After systemic administration to neuropathic pain model rats, the lead antibody produced robust analgesia lasting at least 96 h. Electrophysiological analyses demonstrated reduced mechanically evoked and spontaneous neuronal activity, and immunohistochemistry showed decreased mechanical stimulus-induced phosphorylation of extracellular signal-regulated kinase in dorsal root ganglion neurons. The antibodies did not impair physiological nociception or motor function under the tested conditions. Conclusions: These findings provide preclinical proof of concept that humanized anti-Nav1.7 antibodies can act as systemically administered, long-acting biologic analgesics for neuropathic pain while preserving normal nociceptive and motor functions. The clinical advancement of S-151128 further supports the translational potential of this modality. Full article

Deep dermatophytosis is a rare, life-threatening fungal infection characterised by the invasion of dermatophytes beyond the superficial layers of keratinised tissue into the dermis and subcutaneous tissues. The present review aimed to identify the current knowledge on the role of Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in the pathogenesis, clinical spectrum, diagnosis, and management of deep dermatophytosis. For innate immune activation, CARD9 acts as an adaptor molecule. Basically, CARD9 helps mediate the connection between the fungal pattern recognition receptor (Dectin-1) and the NF-κB and MAPK signalling pathways, and it mediates cytokine production, thereby activating phagocytic activities. Thereby, any change or mutation in the CARD9 gene may disrupt these pathways, leading to dysfunctional neutrophils and impaired Th17-mediated antifungal immunity. Clinically, patients with CARD9 deficiency are immunocompetent but susceptible to recurrent and/or severe fungal infections [Candida, dermatophytes (Trichophyton spp.), and phaeohyphomycetes]. Deep dermatophytosis in these patients is usually chronic, treatment-resistant, and characterized by erythematous papules, nodules, plaques, ulcers, or necrotic lesions, most of which occur on the lower limbs. It usually occurs in adulthood and is more common in males. There have been instances of geographic clustering of CARD9 deficiency in Asia, North Africa, and the Middle East. Early recognition and genetic diagnosis of CARD9 mutations in patients with recurrent or atypical deep dermatophytosis. Although antifungal therapy is essential, hematopoietic stem cell transplantation can be a definitive treatment for selected patients with CARD9 deficiency. Thus, CARD9 deficiency is a critical factor in the better management of patients but remains an underrecognized cause of severe, treatment-resistant deep dermatophytosis, and early genetic diagnosis is essential for guiding targeted management and improving patient outcomes. This review emphasises the importance of CARD9 in antifungal immunity and underscores the need for greater clinical awareness and the incorporation of genetic evaluation into the management of deep dermatophytosis. Full article

Ascophyllum nodosum extracts (ANE) are widely used biostimulants associated with improvements in plant growth, productivity, nutrient acquisition, and abiotic stress tolerance. However, the molecular mechanisms linking extract composition to plant signaling and physiological responses remain incompletely resolved. ANE contains a complex mixture of bioactive constituents, including polysaccharides, osmolytes, phenolic compounds, and phytohormone-like molecules. Their composition varies according to biomass source, environmental conditions, and extraction methodology, contributing to variability in biological activity. Current evidence suggests that ANE functions mainly as a signaling modulator rather than a direct nutrient source. ANE treatment has been associated with early cellular responses, including cytosolic Ca²⁺ influx, reactive oxygen species (ROS) generation, and mitogen-activated protein kinase (MAPK)-associated signaling events. However, many proposed mechanisms remain unresolved, and a considerable proportion of the available mechanistic evidence originates from studies using purified ANE-derived polysaccharides or related elicitor systems. ANE-associated responses include modulation of nutrient transport, primary metabolism, hormonal regulation, transcriptional reprogramming, and stress-responsive pathways, contributing to improved root development, nutrient acquisition, and defense-related responses. Nevertheless, limited knowledge of receptor-mediated perception mechanisms, signaling hierarchies, and extract-dependent variability continues to constrain mechanistic understanding and reproducibility. Future research should prioritize receptor identification, bioassay-guided fractionation, integrated multi-omics approaches, and improved standardization of extraction and formulation procedures. These advances will be essential for establishing robust mechanistic models and supporting the development of evidence-based ANE biostimulants for sustainable crop production. Full article

The skin serves as the body’s first line of defense against environmental threats, acting as a barrier between external aggressors and internal systems. Current evidence regarding the roles of sulfur dioxide (SO₂) in biology and medicine is limited. Environmental pollutants, including SO₂, can increase the production of reactive oxygen species in the skin, leading to oxidative damage that may worsen various dermatological conditions. Endogenous SO₂, proposed as the fourth member of the gasotransmitter family, functions as a biological signaling molecule. It is generated in various human skin cells, including vascular smooth muscle cells, endothelial cells, mast cells, keratinocytes, macrophages, adipocytes, fibroblasts, dermal immune cell population, etc, where it performs multiple functions at physiologically relevant concentrations. Endogenous SO₂ plays a crucial role in regulating cell signaling and maintaining skin homeostasis through its antioxidant, anti-inflammatory, and cytoprotective effects. Abnormal generation and metabolism of SO₂ are linked to several critical processes in the skin, including vascular biology, immune response, cell proliferation, pigmentation, malignancy, protective barriers, senescence, and resistance to stress. This paper provides a narrative review of the significant roles of SO₂ in skin health and disease. A comprehensive understanding of the complex molecular effects and mechanisms mediated by SO₂ in human skin, along with the development of gas therapy, will be essential for translating fundamental research into clinical applications. Full article

Declines of skeletal muscle mass and functions are implicated in the progression of various clinical conditions such as cancers, obesity, insulin resistance, diabetes, and osteoporosis. While no effective and safe drugs against muscle wasting, such as sarcopenia and disease-associated cachexia, have been discovered, it is well documented that dietary essential amino acids (EAAs) or high-quality protein work synergistically to enhance the anabolic effect of resistance exercise training (RT), leading to gains in muscle mass, strength, and muscle quality. Dietary EAAs serve as precursors and signaling molecules for the synthesis of new muscle proteins (both contractile and mitochondrial) and stimulate neuromuscular junction remodeling. Furthermore, EAAs consumed in the post-absorptive state improve endurance capacity via stimulation of mitochondrial biogenesis (independent of PGC1-α) and mitochondrial dynamics (mitochondrial protein synthesis and fission). Here, we discuss (1) traditional molecular mechanisms regulating the muscle proteome through constant turnover (synthesis and breakdown), (2) novel mechanisms by which dietary supplementation of EAAs during RT simultaneously improves muscle strength and endurance, (3) stable isotope tracer methodologies that enable understanding of the dynamic muscle proteome and accurate assessment of functional muscle mass, and finally, (4) clinical implications of combined EAA and RT interventions in the context of muscle and metabolic dysfunction, including sarcopenia, cachexia, obesity, and chronic disease. Collectively, current evidence underscores the potential of balanced EAAs, particularly when combined with resistance training, as a safe, effective, and translationally relevant nutritional strategy to preserve and enhance muscle and metabolic health across healthy and clinical populations. Full article

Lipids are commonly viewed as membrane components, energy sources, or precursors of signaling molecules, yet accumulating evidence indicates a broader role in determining the functional state of cells. In this review, we present an integrative cross-domain synthesis in which lipids are discussed as important modulators of cellular functional state across inflammation, tissue regeneration, and chronic disease. We discuss how membrane lipid composition shapes receptor and ion-channel signaling, how bioactive lipid mediators govern the balance between inflammatory initiation and resolution, and how lipid metabolism regulates stem-cell quiescence, activation, and regenerative capacity. We integrate these mechanisms to show how disruption of lipid-regulated processes may bias tissues toward persistent inflammation, impaired repair, and disease progression in conditions such as rheumatic disorders, fibrosis, and neurodegeneration. Depending on context, such lipid alterations may function as causal contributors, permissive conditions, or downstream signatures of pathological state transitions. Finally, we consider how pharmacological and nutritional modulation of lipid pathways may influence cellular states, while emphasizing that the main contribution of this review is a conceptual state-transition framework that links membrane architecture, mediator balance, and lipid metabolic flux across inflammation, regeneration, and chronic disease. Full article

Background: Gentamicin-induced nephrotoxicity limits clinical pharmacotherapy and involves multiple converging stress-response pathways. Ellagic acid (EA) has renoprotective potential, yet its role in coordinating endoplasmic reticulum (ER) stress-mediated apoptosis, autophagy, and inflammation remains unclear. We hypothesized that EA co-treatment would protect the kidney by modulating ER stress-dependent pathways and associated inflammatory and adaptive signaling. Methods: For an integrated mechanistic analysis in a rat model of gentamicin nephrotoxicity, 40 male Sprague-Dawley rats were assigned to control, gentamicin (100 mg/kg), EA (100 mg/kg), and gentamicin + EA groups for 14 days. Renal function, oxidative stress, inflammatory mediators, ER stress markers, apoptosis, autophagy, tubular injury markers, and histopathological changes were assessed. Results: Gentamicin induced renal dysfunction, tubular injury, and ER stress across all unfolded protein response (UPR) branches (IRE1α, PERK, ATF6), C/EBP homologous protein (CHOP)-associated apoptosis, dysregulated autophagy, and upregulated kidney injury molecule-1 (KIM-1). A selective inflammatory signature was observed, with increased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6), whereas tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) remained unchanged. Co-administration of ellagic acid with gentamicin significantly improved renal function markers compared to the gentamicin group. In contrast, ellagic acid alone did not show significant differences compared to the control group. Notably, gentamicin induced compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) expression, while ellagic acid co-treatment attenuated this compensatory upregulation, likely secondary to reduced oxidative stress burden. Conclusions: This study provides integrated evidence that ER stress is closely associated with gentamicin nephrotoxicity. The key novel findings include selective suppression of IL-6, modulation of the apoptosis-autophagy balance, and attenuation of Nrf2/HO-1 signaling without direct reactive oxygen species (ROS) scavenging, demonstrating a multi-target framework for EA’s renoprotective effects. These findings suggest that ellagic acid mitigates renal injury in a context-dependent manner rather than confirming a direct causal mechanism. Full article

Cancer stem cells (CSCs) constitute a resilient tumor subpopulation responsible for multidrug resistance, metastasis, and clinical relapse. A cardinal hallmark of these cells is profound metabolic plasticity. This dynamic defense mechanism facilitates rapid shifts between glycolysis, oxidative phosphorylation (OXPHOS), and alternative nutrient catabolism, enabling CSCs to bypass microenvironmental constraints. This review delineates how glycolytic adaptation functions as a primary driver of therapy resistance within the CSC niche. We dissect the regulatory triad controlling these metabolic shifts, which includes rate-limiting enzymes, epigenetic and epitranscriptomic remodeling, and master transcription factors. Glycolytic reprogramming transcends bioenergetics by acting as a metabolic signaling node. It integrates with the epithelial–mesenchymal transition (EMT) program, autophagic pathways, and the immunosuppressive tumor microenvironment (TME) to fortify CSC survival. We appraise emerging therapeutic interventions targeting these metabolic vulnerabilities. Strategies focus on optimizing small-molecule inhibitors, nanotechnology-enabled delivery systems, and immunometabolic combination regimens. This review establishes a conceptual framework for precision interventions aimed at disrupting CSC plasticity, overcoming therapeutic resistance, and preventing tumor recurrence. Full article

Chronic kidney disease (CKD) remains a leading cause of premature mortality and global disease burden, yet the molecular mechanisms underlying its progression are still incompletely understood. Accumulating evidence highlights circadian disruption as an underappreciated driver of CKD that warrants systematic re-examination. The kidney harbors an autonomous circadian oscillator, principally regulated by the CLOCK:BMAL1 transcription factor complex, which coordinates glomerular filtration, tubular electrolyte handling, blood pressure rhythmicity, inflammatory tone, and cellular repair. In CKD, retained uremic toxins, sustained oxidative stress, and persistent NF-κB activation collectively suppress this clock machinery, generating a self-reinforcing cycle of renal injury and circadian dysregulation. CKD is also accompanied by progressive attenuation of nocturnal melatonin secretion, weakening a central hormonal cue for peripheral clock entrainment and cytoprotection. Melatonin acts both as a chronobiotic and as a pleiotropic cytoprotective molecule. Through MT1/MT2 receptors, the nuclear receptor RORα, and receptor-independent antioxidant pathways, it may enhance Nrf2/HO-1 signaling, restrain NF-κB and NLRP3 inflammasome activity, suppress TGF-β1/Smad2/3-mediated fibrogenesis, preserve mitochondrial integrity, and engage SIRT1-linked clock regulation. Current clinical studies suggest that nightly melatonin supplementation can improve sleep quality and selected oxidative or circadian surrogate endpoints in hemodialysis patients; however, whether melatonin slows CKD progression or preserves renal function remains unproven. This review synthesizes the molecular interface between circadian dysregulation and CKD progression and articulates a rationale for adequately powered clinical trials evaluating melatonin as a candidate chronotherapeutic adjunct rather than an established renoprotective therapy. Full article

Background: Recent technology improvements have enabled desorption electrospray ionisation (DESI) mass spectrometry imaging to achieve down to 5 µm (pixel) image resolution. However, operating at this resolution introduces challenges, particularly regarding increased total analysis time and the need for sufficient instrument sensitivity to detect analytes from very small tissue areas. Methods: High mass and image resolution DESI imaging was performed on rat brain tissue using a Xevo™ MRT benchtop mass spectrometer equipped with a multi-reflecting time-of-flight mass analyser and a DESI XS source. Data acquisition was conducted at speeds of up to 100 Hz. Sensitivity was assessed using a dilution series of five Active Pharmaceutical Ingredients (APIs) spotted onto porcine liver tissue. Signal detection limits were evaluated using extracted ion chromatograms (XICs) with signal-to-noise (S/N) calculations against blank samples. Additionally, enhanced duty cycle (EDC) was applied to evaluate improvements in analyte signal intensity across specific mass ranges in both positive and negative ionisation modes. Results: At acquisition speeds of up to 100 Hz, excellent data quality was achieved, with signal intensity remaining suitable for analytical applications. All five tested APIs were detectable at concentrations of 25 pg/mm². Three of the five compounds were further detected at concentrations as low as 2.5 pg/mm², with signal-to-noise ratios greater than 5. The application of EDC resulted in a significant increase in analyte signal intensity within the targeted mass ranges, particularly for small molecule endogenous metabolites and lipids, in both ionisation modes. Furthermore, the system demonstrated substantially improved spectral quality, achieving mass resolution up to 100,000 FWHM. This enabled the resolution of previously indistinguishable analytes with significantly improved mass accuracy compared to systems operating at approximately 30,000 FWHM. Conclusions: The Xevo™ MRT mass spectrometer with DESI XS source enables high-resolution DESI imaging at speeds up to 100 Hz without compromising data quality or sensitivity. The system demonstrates excellent detection limits for pharmaceutical compounds and improved performance through enhanced duty cycle operation. Overall, the combination of high spatial resolution, increased mass resolution, and improved spectral quality allows for more accurate analyte differentiation, representing a significant advancement over lower-resolution systems. Full article

Background: Acquired tolerance to temozolomide (TMZ) remains one of the main obstacles to enduring therapeutic success in glioblastoma (GBM). While tumor-derived extracellular vesicles are known to orchestrate therapy evasion by horizontally transferring molecules across the tumor microenvironment, the precise regulatory roles of specific exosomal circular RNAs (circRNAs) in establishing this refractory state require further elucidation. Methods: The expression of circ_0050688 in TMZ-resistant GBM clinical tissues and cell lines was evaluated. Exosomes derived from resistant cells were isolated and confirmed via transmission electron microscopy (TEM) and marker analysis. PKH67 fluorescent tracking was utilized to visually demonstrate exosome internalization by sensitive recipient cells. Biological functions, including the expression of the multidrug resistance protein P-glycoprotein (P-gp) and the proliferation marker Ki-67, were evaluated. The competing endogenous RNA mechanism was validated using RNA FISH, dual-luciferase reporters, and functional rescue experiments. In vivo efficacy was determined using subcutaneous xenograft mouse models. Results: Clinical and in vitro analyses revealed that circ_0050688 is upregulated in TMZ-refractory GBM, predicting adverse patient survival. Through PKH67-based tracing, we confirmed that resistant cells actively secrete circ_0050688-enriched exosomes, which are subsequently engulfed by drug-sensitive bystander cells. This vesicular transfer directly instigates a chemoresistant and highly proliferative phenotype, marked by elevated P-gp and Ki-67 levels. At the molecular level, circ_0050688 operates as a molecular decoy for miR-508-5p, thereby preventing the suppression of its downstream target, MDM2. Functionally, circ_0050688 depletion eradicated these aggressive traits and restored TMZ vulnerability across both cellular and murine xenograft models. Furthermore, rescue assays confirmed that this circ_0050688-driven chemoresistance is fundamentally dependent on the miR-508-5p/MDM2 signaling axis. Conclusions: Current data uncover an intercellular signaling network driven by vesicular circ_0050688, which functions as a mobile oncogene to reshape the TMZ-refractory microenvironment. Targeting this exosomal circ_0050688/miR-508-5p/MDM2 network to suppress P-gp and Ki-67 expression represents a highly promising therapeutic strategy for refractory GBM. Full article

Dental diseases have long been taught and treated as separate entities: cariology, operative dentistry, endodontics, and periodontology, each working within its own boundaries. However, increasing biological and clinical evidence suggests that this classified view does not fully reflect how disease progresses in the mouth. Instead, dental disease should be understood as a continuum within the interconnected tooth–pulp–periodontium complex. This review provides current evidence showing how dental caries can serve as the starting point of a process that can progress through pulpitis and apical periodontitis and eventually affect surrounding periodontal tissues. Caries is now widely known as a biofilm-driven and host-influenced condition shaped by ecological imbalance rather than specific pathogens alone. As lesions penetrate deeper into dentin, the structure becomes more permeable, permitting diffusion of microbial metabolites and signaling molecules toward the pulp. This initiates a multifaceted inflammatory reaction within the pulp tissue. At this stage, pulpitis becomes a critical turning point, where the outcome depends on microbial load, lesion activity, host response, and quality of clinical intervention. If the disease is not well controlled, it may lead to pulp necrosis, allowing infection to spread beyond the root canal and initiate periapical inflammation. Through anatomical pathways such as apical foramina and lateral canals, these processes can extend further, sometimes resembling or overlapping with periodontal disease. This overlap creates diagnostic challenges, as conventional tests may not always distinguish between conditions. A structured, pathway-based diagnostic approach is therefore essential. From a treatment perspective, this continuum model highlights early intervention, minimally invasive care, preservation of pulp vitality when possible, and maintenance of a strong coronal seal. Ultimately, stronger integration across dental disciplines can improve diagnosis, guide treatment decisions, support long-term tooth preservation, and promote unified dental education. This article presents a narrative review supported by a structured literature search and proposes a clinically actionable framework that extends established endodontic–periodontal concepts upstream to include caries initiation and restorative modulation. Full article

Background and Objectives: Temporomandibular disorders (TMDs) encompass a broad spectrum of functional and structural abnormalities of the temporomandibular joint (TMJ). Conventional diagnostic tools, although essential, often fail to capture the underlying biochemical mechanisms driving disease progression. Synovial fluid (SF), by virtue of its direct proximity to intra-articular tissues, represents an accessible biological matrix for identifying molecular signatures of inflammation, cartilage degradation, lubrication failure, oxidative stress, and angiogenic activation. The objective of this review is to synthesize current evidence on SF proteomics in TMD and evaluate its potential translational value in precision medicine. Materials and Methods: A narrative review of the literature was conducted on PubMed to identify human studies focused on SF proteomic and biochemical biomarkers in TMD. Eligible studies included original research articles assessing SF composition in relation to specific TMJ pathologies, diagnostic categories, or clinical phenotypes. Extracted data included study design, sample characteristics, analytic methodology, biomarkers investigated, and key findings. Google Gemini (Google LLC, Mountain View, CA, USA) was used as an AI-assisted tool to support language editing and manuscript writing during the preparation of this article. The use of this tool was limited to linguistic refinement; all scientific content, data interpretation, and conclusions were formulated and verified by the authors. Results: Across the analyzed studies, TMD phenotypes—particularly disc displacement with or without reduction (DDwR, DDwoR) and osteoarthritis (OA)—were characterized by consistent alterations in cytokines (IL-1β, IL-6, IL-8, TNF-α), extracellular matrix (ECM) components (aggrecan, glycosaminoglycans (GAGs), decorin, MMP-2, MMP-9), lubrication molecules (lubricin/PRG4), oxidative stress mediators (myeloperoxidase (MPO), nitric oxide (NO), glutathione peroxidase (GPX)), adipokines (chemerin, resistin, adiponectin), and angiogenic factors (vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2)). Recent liquid chromatography–tandem mass spectrometry (LC–MS/MS) analyses further revealed phenotype-specific protein clusters and pathways related to inflammation, ferroptosis, hypoxia signaling, and proteoglycan metabolism. Conclusions: Current evidence suggests that SF proteomics and multi-analyte biomarker profiling offer a promising, hypothesis-generating approach for understanding the biological mechanisms underlying TMD. The integration of proteomic, metabolic, and inflammatory markers holds future potential for diagnostic panel development; however, prospective clinical validation is still required before SF-based molecular profiling can be implemented as a precision medicine tool in TMJ disorders. Full article

Neurodegenerative disorders and epilepsy remain major clinical challenges, due to complex etiologies involving protein misfolding, excitotoxicity, metabolic dysregulation, and impaired cellular resilience. These unmet medical needs have stimulated interest in small-molecule modulators capable of targeting multiple pathogenic pathways. Cyclitols, a diverse family of inositol stereoisomers, play essential roles in cellular signaling and brain metabolism; among them, scyllo-inositol (SCI) has gained attention due to its distinct stereochemistry, capacity to cross the blood–brain barrier, and emerging neuroactive properties. Current pharmacokinetic data indicate that SCI exhibits dose-dependent systemic exposure, and good penetration into the central nervous system. Moreover, its supplementation seems to be well-tolerated. In experimental studies both on animals and humans, SCI has been shown to modulate amyloid-β aggregation, stabilize neuronal homeostatic pathways, and reduce network hyperexcitability, suggesting relevance for both neurodegenerative and epileptic phenotypes. Despite promising results, there is still a need for further analyses to define dosing, transporter involvement, and brain exposure thresholds. Collectively, the available data position SCI as a compelling candidate for translational development, warranting further investigation into its therapeutic window and disease-modifying potential across neurological disorders. Full article