Search Results (8,061)

Zinc is an essential micronutrient involved in many physiological processes in the human body, including immune system regulation, cellular survival, neurologic function, and erythropoiesis. Zinc deficiency can result in a wide range of clinical manifestations, including impaired immune function, dermatologic findings, and decreased growth. Anemia has been reported as a hematologic manifestation of zinc deficiency and may be underrecognized in clinical practice. This narrative review examines the pathophysiology of zinc deficiency-associated anemia, highlighting zinc’s role in erythropoiesis, heme biosynthesis, and red blood cell stability. It also outlines populations at increased risk for zinc deficiency, including patients with chronic kidney disease, sickle cell disease, malabsorptive disorders, chronic proton pump inhibitor use, and older adults. Emerging evidence suggests that zinc deficiency-associated anemia may represent a potentially modifiable contributor to anemia in selected at-risk populations, although the strength of evidence varies across clinical settings and study designs. Assessment of zinc status may be considered in patients with unexplained or refractory anemia and additional risk factors for deficiency. Further prospective studies are needed to clarify the role of zinc deficiency in anemia and define appropriate screening, supplementation, and monitoring strategies. Full article

Background and Objectives: Ovarian cancer remains the most lethal gynecologic malignancy, largely due to late diagnosis and the limitations of currently available diagnostic tools. Systemic inflammatory markers derived from routine blood tests have emerged as potential low-cost biomarkers, reflecting the interaction between tumor biology and the host immune response. This study aimed to evaluate the association and diagnostic value of preoperative inflammatory markers in distinguishing malignant from non-malignant ovarian tumors. Materials and Methods: This retrospective, single-center observational study included 780 adult female patients diagnosed with ovarian tumors and treated surgically between January 2020 and December 2025. Preoperative hematological parameters were obtained from complete blood count analyses performed before any therapeutic intervention. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Comparisons were performed among benign, borderline, and malignant tumors. To avoid collinearity between mathematically interrelated inflammatory indices, three separate multivariable logistic regression models were constructed, each including age, CA-125, and one inflammatory index. Diagnostic performance of the individual inflammatory indices was assessed using receiver operating characteristic (ROC) curve analysis. Results: Patients with malignant tumors were significantly older and exhibited higher NLR and PLR values and lower LMR values than patients with non-malignant tumors (all p < 0.001). In separate multivariable models adjusted for age and CA-125, higher NLR (OR = 1.79, 95% CI: 1.41–2.27, p < 0.001) and PLR (OR = 1.43, 95% CI: 1.17–1.75, p = 0.001) remained significantly associated with malignant ovarian tumors, whereas higher LMR was inversely associated with malignancy (OR = 0.66, 95% CI: 0.52–0.85, p = 0.001). ROC analysis demonstrated moderate discriminative ability for NLR and PLR (AUC = 0.72 for both), whereas LMR showed lower discriminative performance (AUC = 0.64). Conclusions: Preoperative systemic inflammatory indices are significantly associated with ovarian tumor malignancy. NLR and PLR were positively associated with malignant disease, whereas LMR showed an inverse association, and these relationships remained significant after adjustment for age and CA-125. However, their individual discriminative performance was modest, suggesting that these readily available inflammatory indices should be considered complementary rather than standalone biomarkers for preoperative risk assessment. Full article

Metabolic syndrome (MetS) is a clinical condition defined by the coexistence of interconnected cardiometabolic risk factors, including central obesity, dyslipidemia, elevated blood pressure, and impaired glucose regulation, which collectively increase the risk of type 2 diabetes mellitus and cardiovascular disease. Beyond these clinical diagnostic features, MetS is characterized by complex pathophysiological alterations involving systemic dysregulation of metabolic signaling across adipose tissue, skeletal muscle, liver, vascular endothelium, and the immune system. Key molecular alterations include impaired insulin receptor substrate (IRS)–Akt signaling, chronic nuclear factor kappa B (NF-κB) activation, mitochondrial dysfunction, and oxidative stress. Physical exercise is recognized as a pleiotropic biomedical intervention capable of restoring metabolic homeostasis through coordinated modulation of intracellular signaling pathways and inter-organ communication. Exercise activates AMP-activated protein kinase (AMPK), enhances peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis, and stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant responses. These adaptations improve glucose uptake, enhance fatty acid oxidation, and reduce ectopic lipid accumulation across metabolically active tissues. At the systemic level, skeletal muscle functions as an endocrine organ by releasing myokines such as irisin, interleukin-6 (IL-6), and fibroblast growth factor 21 (FGF21), which contribute to metabolic regulation across the liver, adipose tissue, and vasculature. These exercise-induced signals promote immune modulation, reduce pro-inflammatory cytokine production, and improve endothelial function. Different exercise modalities including aerobic, resistance, and high-intensity interval training (HIIT) activate both common and modality-specific molecular pathways, supporting individualized exercise strategies. Collectively, exercise targets the multi-organ pathophysiology of MetS and provides a mechanistic foundation for precision exercise medicine in cardiometabolic disease management. Full article

Background/Objectives: This study assessed the impact of variations in autophagy-related genes (ATG) on baseline characteristics of cutaneous melanoma, laboratory parameters (including inflammatory biomarkers), response to therapy, and survival in patients treated with immune checkpoint inhibitors (ICIs) as first-line therapy. Methods: DNA was extracted from blood samples of 144 melanoma patients. Genotyping of ATG5 (rs2245214 and rs510432), ATG10 (rs1864183 and rs1864182), and ATG16L1 (rs2241880) was performed using an allelic discrimination method on the StepOnePlus^TM Real-Time PCR System. Correlations with laboratory parameters, response to therapy, and survival were assessed only in the subgroup of patients who received ICIs in first-line treatment (n = 74). Statistical significance was calculated, and p values were adjusted for multiple testing using the Benjamini–Hochberg False Discovery Rate (FDR). Results: Considering baseline characteristics of 144 patients, ATG5 rs2245214 showed a trend with regression (p = 0.042) and lymphovascular invasion (p = 0.05), while ATG16L1 rs2241880 was associated with lymphovascular invasion (p = 0.056), with corrected FDR q value for all histopathological characteristics of 0.076. In patients who received ICIs in first-line, ATG5 rs2245214 genotypes were associated with LDH (p = 0.001, q = 0.004) and the number of metastatic sites (p < 0.001, q = 0.004). Also, ATG5 rs2245214 was associated with neutrophil-to-lymphocyte ratio (NLR) (p = 0.036, q = 0.045) systemic immune-inflammation (SII) index (p = 0.038, q = 0.048) and pan-immune-inflammation value (PIV) (p = 0.031,q = 0.041), while ATG10 rs1864183 was associated with PIV (p = 0.047, q = 0.047). The association of ATG genotypes with disease control rate (DCR) was demonstrated for ATG5 rs2245214 (p = 0.013, q = 0.029) and ATG16L1 rs2241880 (p = 0.032,q = 0.032). Progression-free survival (PFS) was significantly associated with ATG10 rs1864183 (p = 0.023, q = 0.046). The significance of the ATG10 rs1864183 C/T genotype as a prognostic marker for progression was confirmed in both univariate and multivariate Cox proportional hazards regression analyses (p = 0.025, q = 0.028 and p = 0.022, respectively). Conclusions: This study shows that ATG5 rs2245214, ATG10 rs1864183, and ATG16L1 rs2241880 correlate with systemic inflammation, response to ICIs, and had a trend toward melanoma characteristics. However, these findings should be confirmed in larger patient cohorts. Full article

Neurologic manifestations of long COVID, also called neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC: NP) include persistent alteration of cognitive functions. We investigated whether these could be driven by immune perturbations. We combined flow cytometry (FC), sleep profiling, and single-cell RNA sequencing of peripheral blood immune cells from older adult (>55 years) individuals with and without NP to evaluate relationships with objective cognitive performance. NP participants showed reduced numbers of blood monocytes with increased mitochondrial superoxide, indicating an altered monocyte mitochondrial redox state. Higher peripheral capillary oxygen saturation (SpO₂) was associated with better processing speed in NP participants. Monocyte transcriptional analyses identified mitochondrial adenosine triphosphate (ATP) synthase/Complex V (Complex V) pathway associated with cognitive performance in people without NP; this coupling was abrogated in NP patients, in whom cognitive performance instead showed an opposite relationship with Complex V. Shared leading-edge genes defined a 13-gene monocyte anchor representing this cognition-associated NP phenotype. Higher anchor scores were associated with coordinated oxidative phosphorylation and cytotoxic programs across CD3⁺ T-cell subsets in individuals without NP, but not in NP participants. T-cell receptor stratified analyses showed that this altered relationship occurred in both expanded and unexpanded T-cell populations. FC correlations also supported reduced monocyte-to-lymphocyte mitochondrial coordination in NP. These exploratory findings identify a sleep and cognition-linked monocyte mitochondrial phenotype characterized by altered myeloid–lymphoid immune coordination in NP. Full article

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine–metabolic disorder frequently associated with insulin resistance (IR) and increased cardiovascular risk. Soluble CD40 ligand (sCD40L) and soluble E-selectin (sE-selectin) are circulating biomarkers reflecting immune activation and endothelial dysfunction, respectively. However, their differential associations with IR in PCOS, particularly in the context of central obesity, remain incompletely understood. This cross-sectional study included 80 women with PCOS stratified according to waist-to-height ratio (WHtR > 0.50 vs. ≤0.50). Clinical, metabolic, hormonal, inflammatory, and endothelial parameters were evaluated. Correlation and multivariable regression analyses were performed to identify independent determinants of circulating sCD40L and sE-selectin. Women with central obesity exhibited significantly higher fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, systolic blood pressure (SBP), and sE-selectin concentrations, together with lower HDL cholesterol. No significant differences were observed in tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), or sCD40L. In adjusted regression models, fasting glucose independently predicted sCD40L (β = −0.27, 95% confidence interval (CI): −0.50 to −0.04, p = 0.020), whereas fasting insulin emerged as the strongest determinant of sE-selectin (β = 0.41, 95% CI: 0.17 to 0.65, p < 0.001). These findings suggest distinct associations of immune and endothelial biomarkers with IR in PCOS. Assessment of sCD40L and sE-selectin may provide complementary information for early cardiometabolic risk stratification in affected women. Full article

Extracellular vesicles (EVs) are crucial mediators of intercellular communication in the tumor microenvironment (TME) which facilitate the transfer of bioactive molecules including functional mitochondria and their integral components. This review summarizes the emerging role of EV-mediated mitochondrial transfer in cancer progression. We delineate the mechanisms governing the packaging of mitochondria and their constituents into EVs and subsequently highlight their multifaceted functions across various malignancies, including breast cancer, prostate cancer, blood malignancies, head and neck squamous cell carcinoma, digestive system cancers, etc. Mitochondrial cargo, such as intact mitochondria, mitochondrial DNA (mtDNA), and RNA (mtRNA), are shown to reconfigure metabolism, enhance bioenergetics, promote proliferation and invasion, induce drug resistance, and remodel TME by suppressing antitumor immunity. While previous reviews have predominantly focused on the role of mitochondrial transfer in individual cancers or specific systemic diseases, we made a comprehensive overview encompassing diverse cancer types. These findings suggest that EV-mediated mitochondrial cargo transfer represents a biological intercellular communication mechanism with implications for tumor progression and therapeutic resistance. It is worth noting that we also apply standardized evidence-grading frameworks (C1–C4) across cancer types to provide a critical assessment of the current evidence and identify key methodological gaps that must be addressed in future studies. Collectively, this review underscores the significance of EV-mediated mitochondrial transfer as an important biological process in cancer, presenting it as a promising frontier for novel diagnostic and therapeutic interventions. Full article

The problem: Johne’s disease, caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP), can be widespread in cattle herds. As a consequence of the slow progression of the infection and the delayed appearance of a humoral response, at any time few of the infected animals may be detected as positive with current serological tests. Many disease control initiatives have focused on removing infected animals by using serology to detect antibodies, principally to a purified MAP extract. However, the delayed humoral response to MAP extract, which can be preceded by shedding MAP in the faeces, limits the value of this control method. The approach: We used a longitudinal study to evaluate the timing and magnitude of antibody responses to lipid antigens. The method: Thirty breeding females from a beef cow herd with a history of Johne’s disease were recruited at 10–12 months old. Blood (serum) and faecal samples were collected at six-month intervals over five years. The serum samples were evaluated by enzyme-linked immunosorbent assay (ELISA) using six synthetic lipid antigens, each from a different class of chemical compound that are components of the mycobacterial cell wall. The responses were correlated with MAP infection status as determined by faecal culture, a commercial serum antibody ELISA (ID Screen^®), and interferon-γ release assays. Nineteen animals were positive using either culture or ID Screen^® at one or more time points; eleven animals were never positive in either assay. Results: In the lipid ELISA, the median responses for all animals were significantly higher at time point 5 (when the animals were three years old) than those at earlier time points. The timing of this response is compatible with, but does not prove, a shift in immune-response profile. For the antigens MOD171 and RT237F2, the responses for each individual animal were higher at time point 5 than at time point 4. Outcome: The increase in response to lipid antigens MOD171 and RT237F2 between the ages of two and four years may indicate infection with MAP at an earlier stage than is achieved with the established serology tests. Full article

Background: Staphylococcus aureus (SA) causes septicemia and arthritis, eventually resulting in substantial economic losses and health hazards in poultry. Lethal electron beam (eBeam) treatment kills bacteria while preserving surface epitopes. Methods: This study compared broiler chicken immune responses (local and systemic) after eBeam-killed (eB) or formalin-killed (FK) SA injections. The vaccine (sham) control was endotoxin-free PBS. This study contained six treatments (trt) with five chickens/trt, with vaccine trts divided into two groups, A and B. Group A received in ovo vaccine/sham treatments (phase 1) initially. At 34 d of age, the pulps of growing feathers (GFs) received intradermal (i.d.) injections of the respective trt to elicit booster and primary responses in groups A and B, respectively. Blood was collected to analyze leukocyte populations and plasma SA-specific antibody levels. Additionally, in phase 2, GFs were collected to assess leukocyte presence in GF pulps. Two-way ANOVA was conducted to test the effects of treatment, time, and their interactions, followed by Tukey’s HSD tests at p < 0.05 for statistical significance. Results: Early in phase 1, the eB group had increased SA-specific IgM, IgA, and total lymphocyte concentrations compared with FK. In phase 2, FK and eB i.d. vaccines increased total lymphocyte and T cell proportions in GF pulps compared with sham. In blood, the recall eB vaccination increased monocytes, B cells, CD8+ T cells, and total lymphocytes, while the recall FK vaccination increased heterophils (p < 0.05). Conclusions: Improved early protection at mucosal surfaces may be reflected by higher plasma levels of SA-specific IgM and IgA following in ovo eBeam-killed-SA vaccination. Additionally, both eB-SA and FK-SA vaccines stimulated robust local inflammatory responses dominated by lymphocytes in GF pulps. Full article

The liver is an immunologically distinctive organ. Portal blood continuously delivers gut-derived antigens and microbial products, requiring hepatic immunity to balance surveillance with restraint. In hepatocellular carcinoma (HCC), this physiology is commonly overlaid by chronic injury, inflammation, and fibrosis, so the background liver forms part of the disease context in which the tumor microenvironment (TME) develops. This review synthesizes how cellular architecture, tumor-intrinsic programs, and structural, metabolic, and microbial conditions interact to shape immune evasion and heterogeneity. HCC provides the principal evidence base, with intrahepatic cholangiocarcinoma (iCCA) used as a structured, biologically distinct comparator. We organize therapies by the microenvironmental barriers they are intended to modify and distinguish established clinical efficacy from evidence that the proposed mechanisms mediate treatment benefit. Single-cell and spatial studies have resolved cellular states and spatial arrangements, including onco-fetal endothelial–myeloid neighborhoods and a macrophage–fibroblast boundary band separating lymphocyte-rich stroma from malignant tissue. These patterns operate within fibrotic and metabolically altered tissue and vary by etiology, spatial context, and tumor type. Vascular endothelial growth factor blockade with immune checkpoint inhibition and dual checkpoint blockade are established first-line options in advanced HCC. Chemo-immunotherapy is established in biliary tract cancer, and IDH1 inhibition has established efficacy in IDH1-mutant cholangiocarcinoma. Myeloid- and stroma-directed strategies, natural-product approaches, and engineered-cell therapies remain preclinical or early clinical. None of the pivotal trials tested whether the proposed microenvironmental mechanism mediated treatment benefit. The liver TME informs treatment selection without yet determining it. Full article

Background: Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 25% to 40%. A 2026 outbreak aboard an expedition cruise ship in the South Atlantic, comprising 13 cases and three deaths, confirmed that Andes virus can be transmitted between humans in a confined setting remote from the rodent reservoir. Methods: Virological, pathophysiological, clinical, and therapeutic aspects of HPS were reviewed, with particular emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, Scopus, and Google Scholar, with priority given to original research articles, clinical series, and controlled trials published through 2025. Literature published in English and Spanish was included. Results: Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. Because the incubation period is long and the cardiopulmonary phase is substantially immune-mediated, seroconversion precedes rather than follows clinical deterioration, which preserves the diagnostic utility of IgM serology in a disease that can kill within 48 h. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase, and no licensed vaccine exists. Conclusions: HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and concurrent hantavirus IgM serology and RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure. Full article

Background: The skin barrier plays a fundamental role in preventing transepidermal water loss (TEWL), regulating immune responses, and protecting against pathogen colonization. Disruption of this barrier underlies xerosis, sensitive skin, and clinical cracking. Heat-treated probiotics (postbiotics) represent a stable and biologically active approach to topical formulation. Objective: To evaluate the safety, molecular mechanisms, and clinical efficacy of heat-treated Lactiplantibacillus plantarum Skinbac™ SB14 (SB14) in improving skin barrier function, hydration, and the appearance of dry and cracked skin. Methods: In vitro studies assessed cell viability (MTT assay) and cytotoxicity (LDH release assay), Aquaporin-3 (AQP3) expression, Claudin-1 expression recovery following UV-induced damage (post-damage treatment model), cytokine modulation in Normal Human Epidermal Keratinocytes (NHEK) and Peripheral Blood Mononuclear Cells (PBMCs), and antipathogen activity against Staphylococcus aureus biofilm. A 30-day open-label, placebo-controlled clinical study (n = 20 healthy volunteers, both sexes, age > 18 years) evaluated an emulsion containing 1% SB14 versus placebo using instrumental measurements of superficial hydration (Corneometer^® CM825) and TEWL (Tewameter^® TM300), and clinical scoring of skin hydration (Kligman scale 1–4) and skin cracking (ODS Overall Dry Skin Score 1–5) via C-Cube imaging. Results: In vitro testing confirmed the safety of SB14 (full cell viability by MTT assay; no cytotoxicity by LDH release assay) and demonstrated significant AQP3 upregulation (p < 0.05), partial Claudin-1 recovery in UV-damaged cells following post-damage SB14 application (p < 0.1 vs. UV damage), significant reduction in pro-inflammatory IL-8 and IL-23 in NHEK (p < 0.01 and p < 0.05), strong innate immune activation in PBMCs (TNF-α and IL-6, p < 0.001), and 21% inhibition of S. aureus biofilm at 72 h. Clinically, the SB14 formulation significantly increased superficial skin hydration by +46.1% at T14 (p = 0.0451) and +33.6% at T30 (p = 0.0144) versus baseline, while TEWL decreased by −14.5% at T14 (p = 0.0205). Clinical hydration scores improved significantly from a median of 3.0 (moderate dry skin) at baseline to 2.0 (slightly dry skin) at T30 (p = 0.0073). Cracking scores improved significantly from a median of 3.5 at baseline to 2.0 at T30 (p = 0.0037), with 80% of subjects showing improvement at T30. All parameters remained non-significant in the placebo group. No adverse events were reported. Conclusions: SB14 is safe, biologically active across multiple barrier-relevant mechanisms, and clinically effective in improving hydration and reducing visible skin cracking in subjects with dry, barrier-compromised skin. Full article

Background: Conventional cardiovascular risk scores do not directly characterize immune checkpoint-expression phenotypes in people with HIV. We examined patient-level alignment between SCORE2 and PD-1/PD-L1 checkpoint expression in a secondary analysis of a previously characterized parent cohort. Methods: Data from 100 PWH followed at a single HIV center were analyzed. SCORE2, lipid parameters, systolic blood pressure, CD4+/CD8+ ratio, and flow-cytometric PD-1/PD-L1 expression on T-cell, B-cell, and NK-cell subsets were assessed at baseline and after 12 months. Composite immune-exhaustion indices were derived from standardized checkpoint-marker values. Discordance profiles were defined using quartile thresholds for endpoint SCORE2 and immune exhaustion. Results: Smokers had higher endpoint SCORE2 than nonsmokers (median 3.5% vs. 1.0%; p = 0.001), but smoking was not associated with higher composite or individual checkpoint-defined exhaustion. Endpoint SCORE2 correlated with classical cardiovascular variables but not with the composite exhaustion index (ρ = 0.075; p = 0.468) or individual PD-1/PD-L1 markers. Discordant cardiovascular–immune profiles were observed in 10 of 96 evaluable participants (10.4%). Conclusions: SCORE2 and PD-1/PD-L1 checkpoint-expression profiles showed limited contemporaneous alignment in this cohort. The identified discordant profiles are exploratory and require external validation. Full article

Background: Aggression and violence are complex behavioral phenomena with substantial biological underpinnings involving immune activation and lipid metabolism. Previous evidence has linked inflammatory signaling and altered cholesterol homeostasis to impulsive and antisocial behaviors. The present exploratory study investigated differential gene expression patterns associated with severe violent offending and their relationship with aggression-related phenotypes. Methods: Whole-blood samples from 19 male severe violent offenders and 11 healthy controls were analyzed using Clariom S gene expression arrays followed by qPCR validation. Participants additionally completed psychometric assessments including the State Trait Anger Expression Inventory-II (STAXI-II), the Psychopathic Personality Inventory-Revised (PPI-R), and the Appetitive and Facilitative Aggression Scale (AFAS). Results: Differential expression analysis identified 833 significantly dysregulated genes (FDR < 0.1; fold change ≥ 1.5) in violent offenders relative to controls. Among the most strongly altered genes were IL1B, TLR4, PTGS2 (COX-2), ABCA1, IL6R, PRF1, and MMP9. qPCR validation confirmed significant upregulation of MMP9, PTGS2, IL6R, and PRF1. Gene x behavior analyses demonstrated significant associations between PTGS2 expression and reactive as well as outwardly directed aggression, while MMP9 expression correlated with psychopathy-related traits. Furthermore, several lipid metabolism-related genes, including ABCA1, ABCG1, NPC1, DGAT2, and TLR4, showed expression patterns suggestive of altered intracellular lipid trafficking and lysosomal lipid accumulation. ABCA1 expression correlated positively with outward anger expression (STAXI-II), whereas ABCG1 and TLR4 were negatively associated with inwardly expressed anger (STAXI-II). Conclusions: These findings support a model in which innate immune activation and dysregulated lipid metabolism contribute to aggression-related phenotypes and severe violent behavior. Although exploratory and limited by sample size, the results highlight potential molecular pathways underlying pathological aggression and warrant further investigation in larger cohorts. Full article

Background: Microbiome-based mechanisms have emerged as a key area of investigation in epilepsy, given the growing recognition that gut microbial communities can modulate central nervous system (CNS) function through the gut–brain axis. Epilepsy is a common chronic neurological disorder affecting more than 65 million people worldwide, and despite the availability of anti-seizure medications (ASMs), approximately 30% of patients develop drug-resistant epilepsy. Current ASMs primarily suppress seizures rather than prevent disease progression, highlighting the need for alternative therapeutic strategies. In this context, increasing evidence supports a role for microbiota-dependent pathways in modulating seizure activity and treatment responsiveness. However, the mechanistic basis of these interactions remains incompletely understood. Methods: This narrative review synthesizes findings from the existing literature to examine the role of microbiota-derived metabolites, including neurotransmitters, vitamins, and the polyphenol metabolite S-equol, in gut–brain communication relevant to epilepsy. Evidence was drawn from both preclinical animal models and clinical studies to provide an integrated, mechanistic perspective on how these pathways may influence central nervous system function and seizure susceptibility. Emphasis was placed on studies describing molecular, metabolic, and signaling mechanisms linking the gut microbiome to epileptogenesis and treatment response. Results: Current evidence indicates that communication between the gut and CNS occurs through neural pathways, such as the vagus nerve, as well as through circulating microbial metabolites. These metabolites can cross the intestinal barrier and, in some cases, the blood–brain barrier (BBB), serving as key mediators of host–microbiota signaling. Emerging studies suggest that while some microbial metabolites may directly influence neuronal hyperexcitability and seizure susceptibility, others likely exert secondary or modulatory effects through broader metabolic and immune pathways. However, the precise mechanisms underlying these interactions remain incompletely understood. Conclusions: Some microbial-derived metabolites may serve as promising biomarkers and mechanistic mediators of epilepsy; however, further investigation is needed to define the molecular and cellular pathways through which these metabolites influence seizure susceptibility and epileptogenesis. Full article