Search Results (21,035)

The bilberry is a low-growing plant native to northern Europe. It belongs to the genus Vaccinium. Bilberry is essential in the local diets of some countries and is used as an herbal medicine to manage several ailments. Still, it is not used for commercial farming in many countries. It has recently been known as a great source of naturally available bioactive compounds and colorants. Bilberry is a therapeutic fruit acknowledged for its rich flavonoids, anthocyanins, carotenoids, ascorbic acid, phenolic acid, tocopherols, and vitamin content. It is one of the richest sources of natural anthocyanins. The polyphenolic compounds in bilberry provide abundant antioxidant content, which are supposed to be the vital bioactive compounds accountable for various health benefits. Even though bilberry is mostly promoted for eye care or vision improvement. It is also stated to promote antioxidant defense and lower oxidative stress, having antiaging, anti-inflammatory, lipid-lowering, antimicrobial effects, lowering blood glucose and other age-related diseases, etc. Reports suggest that apart from the fruit, the leaves of bilberry are equally rich in numerous bioactive compounds of medicinal importance. This current review offers valuable insights on bilberry fruits, leaves, and extracts, providing an inclusive assessment of their bioactive compound configuration, related biological prospects, and the extraction methodology of their major compounds. This review offers a summary of the existing information on the antiaging potential of bilberry fruits and leaves, and analytically reviews the outcome of clinical trials, with special attention towards its medicinal properties. Full article

Background/Objectives: Neovascularization, defined as the sprouting of new blood vessels from pre-existing vasculature, is a critical pathological feature in ocular diseases such as pathological myopia and represents a leading cause of corneal vision loss. Vascular endothelial growth factor A (VEGFA) plays a pivotal role in endothelial cell proliferation, migration, survival by anti-apoptotic signaling, and vascular permeability. Dysregulation of VEGFA is closely linked to pathological neovascularization. Exosomes, nanosized phospholipid bilayer vesicles ranging from 30 to 150 nm, have emerged as promising gene delivery vehicles due to their intrinsic low immunogenicity, superior cellular uptake, and enhanced in vivo stability. This study aimed to investigate whether highly purified mesenchymal stem cell (MSC)-derived exosomes loaded with VEGFA siRNA labeled with FAM can effectively suppress pathological corneal neovascularization (CNV) via targeeted cellular transduction and VEGFA inhibition. Furthermore, we examined whether the therapeutic effect involves the modulation of the PI3K–Akt–Caspase-3 signaling axis. Methods: Exosomes purified by chromatography were characterized by electronmicroscopy, standard marker immunoblotting, and nanoparticle tracking analysis. In vitro, we assessed exosome uptake and cytoplasmic release, suppression of VEGFA mRNA/protein, cell viability, and apoptosis. In a mouse CNV model, we evaluated tissue reach and stromal retention after repeated intrastromal injections; anterior segment angiogenic indices; CD31/VEGFA immunofluorescence/immunoblotting; phosphorylated PI3K and Akt; cleaved caspase-3; histology (H&E); and systemic safety (liver, kidney, and spleen). Results: Exosomes were of high quality and showed peak efficacy at 48 h, with decreased VEGFA mRNA/protein, reduced viability, and increased apoptosis in vitro. In vivo, efficient delivery and stromal retention were observed, with accelerated inhibition of neovascularization after Day 14 and maximal effect on Days 17–19. Treatment reduced CD31 and VEGFA, decreased p-PI3K and p-Akt, and increased cleaved caspase-3. Histologically, concurrent reductions in neovascularization, inflammatory cell infiltration, and inflammatory epithelial thickening were observed, alongside a favorable systemic safety profile. Conclusions:VEGFA siRNA-loaded exosomes effectively reduce pathological CNV via a causal sequence of intracellular uptake, cytoplasmic release, targeted inhibition, and phenotypic suppression. Supported by consistent PI3K–Akt inhibition and caspase-3–mediated apoptosis induction, these exosomes represent a promising local gene therapy that can complement existing antibody-based treatments. Full article

Background/Objectives: Diabetes is characterized by multiple metabolic disorders, defined by high blood sugar levels over a prolonged duration. Type 2 diabetes (T2D) comprises defective insulin secretion, its ineffective utilization, or both, resulting in hyperglycemia. The disease is one of the leading causes of mortality, according to the WHO, and necessitates the development of advanced therapeutics. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. The study and execution of the literature review followed a timeframe of 3–6 months, during which the conceptualization, execution, analysis, writing, and editing were conducted. Ginsenosides, triterpenoids from the Panax genus, are widely recognized for their promising antidiabetic effects, mediated through mechanisms that include glucose uptake, insulin secretion, antioxidant activity, and anti-inflammatory pathways. Ongoing clinical trials in patients with IGT or Type 2 diabetes have shown an improvement in insulin sensitivity and glucose control, and consolidate the therapeutic potential of ginseng pharmacotherapy. Results: This viewpoint summarizes the most recent discoveries on the hypoglycemic mechanisms of ginsenosides for Type 2 diabetes and its associated complications, with a major focus on ginseng-based drug development. An emphasis is placed on how ginsenosides control blood glucose levels and regulate signaling pathways, investigating their antidiabetic mechanisms and potential. Conclusions: Preclinical studies suggest that nano-innovations in ginseng have the potential to address therapeutic challenges, improve systemic circulation, lower the toxicity of biomolecules, and improve bioavailability, defining exciting outcomes. Furthermore, well-designed human clinical trials are necessary to understand the antidiabetic mechanisms and pharmacological potential of ginseng and/or ginsenosides in drug development. Full article

Non-communicable diseases, particularly cardiovascular diseases (CVD) and metabolic syndrome (MS), remain a major challenge for primary health care (PHC). This study aimed to assess cardiometabolic risk and health behaviours in adult PHC patients using routine preventive screening. This prospective observational study included 506 adults attending routine consultations in an urban PHC centre in Poland. Preventive assessment included anthropometric measurements (body weight, height, BMI, and waist circumference), blood pressure, lipid profile, and fasting glucose levels. Health behaviours were recorded using the standardised NFZ CHUK questionnaire. The 10-year CVD risk was estimated using the SCORE2 algorithm. Multivariable logistic regression was used to identify independent factors associated with high cardiovascular risk (SCORE2 ≥ 5%) and of a composite endpoint defined as the presence of any non-optimal biochemical parameter. Nearly half of the participants had excess body weight (overweight or obesity), and more than half met criteria for central obesity. Borderline or elevated total cholesterol was found in 47% of patients, abnormal LDL in 27%, low HDL-C (<40 mg/dL) in 80% (84% when applying sex-specific cut-offs), and impaired fasting glucose or diabetes in about 12%. High SCORE2 risk (≥5%) was observed in approximately 9% of the cohort. In multivariable models, SCORE2 components (age, sex, and smoking) were, as expected, associated with high SCORE2 risk, and obesity (BMI ≥ 30 kg/m²)—a factor not included in SCORE2—was additionally associated with higher risk. Additionally, age, male sex, and obesity also predicted the presence of at least one non-optimal biochemical marker. The prevalence of high SCORE2 risk increased from 1.2% in patients with 0–1 modifiable risk factor to 25.7% in those with 4–5 factors. Lower educational attainment was associated with a higher proportion of high-risk individuals in univariate analysis. Routine preventive activities in PHC enable the identification of important lipid and glucose abnormalities and the clustering of modifiable risk factors, even in a relatively young, highly educated population. Systematic cardiovascular screening and a focus on patients with accumulated risk factors should remain a priority in PHC to enable early identification of high-risk patients and timely implementation of lifestyle and therapeutic interventions. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by persistent memory impairment and complex molecular and cellular pathological changes in the brain. Current treatments, including acetylcholinesterase inhibitors and memantine, only help with symptoms for a short time and do not stop the disease from getting worse. This is mainly because these drugs do not reach the brain well and are quickly removed from the body. The blood–brain barrier (BBB) restricts the entry of most drugs into the central nervous system; therefore, new methods of drug delivery are needed. Nanotechnology-based drug delivery systems (NTDDS) are widely studied as a potential approach to address existing therapeutic limitations. Smart biosensing nanoparticles composed of polymers, lipids, and metals can be engineered to enhance drug stability, improve drug availability, and target specific brain regions. These smart nanoparticles can cross the BBB via receptor-mediated transcytosis and other transport routes, making them a promising option for treating AD. Additionally, multifunctional nanocarriers enable controlled drug release and offer theranostic capabilities, supporting real-time tracking of AD treatment responses to facilitate more precise and personalized interventions. Despite these advantages, challenges related to long-term safety, manufacturing scalability, and regulatory approval remain. This review discusses current AD therapies, drug-delivery strategies, recent advances in nanoparticle platforms, and prospects for translating nanomedicine into effective, disease-modifying treatments for AD. Full article

Introduction: The global prevalence of chronic kidney disease (CKD) is increasing and it is associated with higher mortality rates. Transforming growth factor-beta (TGF-β) can serve as a novel biomarker for early prediction of chronic kidney disease (CKD) progression. Methods: This was a prospective longitudinal study among black patients with CKD who attended the Charlotte Maxeke Johannesburg Academic Hospital between September 2019 and March 2022. Patients provided urine and blood samples for laboratory investigations at study entry (0) and at 24 months follow up. Baseline serum and urine TGF-β1, TGF-β2 and TGF-β3 levels were measured using ELISAs. Multivariable logistic regression analysis was utilized to determine if TGF-β isoforms could predict CKD progression. Results: A total of 312 patients were enrolled at baseline, of whom 275 (88.1%) had early-stage CKD (Stage 1–3). A majority, 95.2% (297/312), of the patients completed the study after 2 years follow up. The prevalence of CKD progression was 47.8% when measured by a sustained decline in eGFR of >4 mL/min/1.73 m²/year or more and 51.9% when measured by a change in uPCR > 30%. The patients with CKD progression had significantly lower eGFR and increased urine protein–creatinine ratios compared to non-progressors. Furthermore, comparing progressors with non-progressors, the median serum TGF-β1 was 21210 (15915–25745) ng/L vs. 24200 (17570–29560) ng/L and the median urine TGF-β3 was 17.5 (5.4–76.2) ng/L vs. 2.8 (1.8–15.3) ng/L, respectively. Baseline serum and urine TGF-β isoforms were unable to discriminate between CKD progressors and non-progressors after multivariable logistic regression analysis. Conclusions: Despite the multiple roles of TGF-β isoforms in kidney disease, baseline levels were not predictive of chronic kidney disease progression. Full article

An early indicator of future cardiovascular risk is lower levels of nighttime blood pressure (BP) dipping from day to night. Prior work has been limited to identifying health behaviors that can promote greater dipping. This pilot study proposes that one possible set of behaviors may be engagement in self-selected leisure activities (SSLAs, or freely chosen non-work activities that are performed with the purpose of relaxation and/or mental escape), which have been linked with reduced daily stress and general daily BP control. Healthy young adult college students [N = 32; 78.1% (n = 25) female, 71.9% (n = 23) white, with an average body mass index (BMI) of 26.31 (SD = 2.46)] visited our laboratory twice within approximately one week. At each visit, the participants were fitted with an ambulatory monitor to collect BP over 24 h. On each day, participants were randomly assigned to either engage in an agreed-upon SSLA or go about their day as usual, except to refrain from engaging in assigned SSLAs; compliance was verified by daily diaries. When accounting for BMI and race/ethnicity, the results showed a higher percentage of BP dipping on the SSLA versus control day for diastolic BP (d = 0.54). SSLAs may be associated with reduced future cardiovascular disease through a nighttime BP dipping effect. Full article

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an immune-mediated neurological disorder driven by dysregulated neuroimmune interactions, yet the molecular architecture linking tumor-associated immune activation, peripheral immunity, and neuronal dysfunction remains insufficiently understood. In this study, we established an integrative computational framework that combines multi-tissue transcriptomic profiling, weighted gene co-expression network analysis, immune deconvolution, and machine learning-based feature prioritization to systematically characterize the regulatory landscape of the disease. Joint analysis of three independent GEO datasets spanning ovarian teratoma tissue and peripheral blood transcriptomes identified 2001 consistently dysregulated mRNAs, defining a shared tumor–immune–neural transcriptional axis. Across multiple feature selection algorithms, ACVR2B and MX1 were reproducibly prioritized as immune-associated candidate genes and were consistently downregulated in anti-NMDAR encephalitis samples, showing negative correlations with neutrophil infiltration. Reconstruction of an integrated mRNA-miRNA-lncRNA regulatory network further highlighted a putative core axis (ENSG00000262580–hsa-miR-22-3p–ACVR2B), proposed as a hypothesis-generating regulatory module linking non-coding RNA regulation to immune-neuronal signaling. Pathway and immune profiling analyses demonstrated convergence of canonical immune signaling pathways, including JAK-STAT and PI3K-Akt, with neuronal communication modules, accompanied by enhanced innate immune signatures. Although limited by reliance on public datasets and small sample size, these findings delineate a systems-level neuroimmune regulatory program in anti-NMDAR encephalitis and provide a scalable, network-based multi-omics framework for investigating immune-mediated neurological and autoimmune disorders and for guiding future experimental validation. Full article

Background/Objective: Early detection of metastatic progression remains a major challenge in precision oncology. Conventional radiological imaging cannot reliably identify micrometastatic disease. Although circulating tumor DNA is promising for minimal residual disease detection, organ-derived response biomarkers reflecting tissue adaptation to secreted factors remain unexplored. We hypothesized that integrating such biomarkers with global laboratory parameters would generate a synthetic variable with improved discrimination for de novo metastasis and mortality. Methods: This prospective observational pilot study enrolled 30 patients (median age 64.4 years; 56.7% female) with heterogeneous solid malignancies. Peripheral blood biomarkers responsive to tumor-secreted soluble factors (n = 11) were quantified using a multiplexed beads Luminex immunoassay. Global analytical parameters (n = 20) were derived from routine laboratory assessments. Hierarchical agglomerative clustering analysis generated two synthetic variables: Stigma (Ϛ) and Qoppa (Ϙ). Receiver operating characteristic curve analysis, Kaplan–Meier survival analysis, and Cox regression were used to evaluate the performance. Results: Qoppa demonstrated acceptable discriminatory performance for de novo metastasis (AUC = 0.78). For mortality prediction, performance varied by disease status (overall AUC = 0.78): superior in non-metastatic patients (AUC = 0.98) but negligible in those with baseline metastases. Kaplan–Meier analysis confirmed significant survival differences (p = 0.042 overall survival; p = 0.024 for metastasis-free survival in the non-metastatic subgroup). Differences in biomarker expression and clinical variables (stage, tumor burden, and metastatic burden) were observed between the high and low Qoppa strata. Conclusions: In this small heterogeneous pilot cohort, Qoppa provides a proof of concept that integrating organ-derived response biomarkers with routine laboratory parameters may capture clinically relevant signals for metastatic risk stratification in oncology patients. This composite parameter supports the generation of hypotheses for future biomarker-driven research and clinical test development. External validation in larger multicenter cohorts is required before clinical implementation. Full article

Lipopolysaccharide (LPS) is widely used to model immune stress in weaned piglets, but it does not fully replicate the pathophysiological alterations induced by live bacterial infection. This study therefore established an oral Salmonella enterica (SE) challenge model and systematically compared its effects with those of LPS to evaluate its potential as a complementary immune stress paradigm. Forty piglets were assigned to five groups: control (saline), LPS (intraperitoneal, 100 μg/kg BW), and three SE groups receiving low-, middle-, or high-dose oral SE (1 × 10⁸ CFU/mL, 2 × 10⁸ CFU/mL, or 3 × 10⁸ CFU/mL in a 10 mL saline volume, respectively). Both LPS and SE significantly reduced average daily gain, while only SE challenge decreased colon length. A transient rectal temperature elevation occurred at 8 h in all challenged groups, persisting at 12 h in the LPS and high-dose SE groups. Serum cytokine analysis revealed that LPS induced early but transient interleukin-12 and tumor necrosis factor-α elevation at 8 h, followed by sustained suppression of interferon-γ, interleukin-6, and interleukin-8. In contrast, the middle-dose SE triggered robust increases in multiple pro-inflammatory cytokines at 24 h. Both challenges significantly reduced the CD4⁺/CD8⁺ T cell ratios in blood and lymphoid organs and decreased intestinal interleukin-10 levels. SE infection produced more severe intestinal pathology, including dose-dependent villus perforations, microvillus disorganization, and mitochondrial cristae vacuolization, beyond the villus shortening and goblet cell reduction observed in both groups. While both LPS and SE induced immune stress and intestinal injury, SE infection caused more severe and comprehensive pathophysiological alterations. Oral administration of 2 × 10⁹ CFU SE for 24 h established a physiologically relevant immune stress model that effectively mimics natural Salmonella infection in weaned piglets, providing a valuable tool for studying enteric diseases and evaluating interventions. Full article

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of the cases of HF worldwide. Among the different phenotypes, cardiometabolic HFpEF has the highest prevalence. Cumulative insults related to cardiometabolic comorbidities—obesity, hypertension and type 2 diabetes—create a milieu of metabolic derangements, low-grade systemic inflammation (i.e., metainflammation), endothelial dysfunction, and coronary microvascular disease. Emerging data indicate that the gut–heart axis is a potential amplifier of this process. Cardiometabolic comorbidities promote gut dysbiosis, loss of short-chain fatty acid (SCFA)-producing taxa, and disruption of the intestinal barrier, leading to endotoxemia and upregulation of pro-inflammatory pathways such as TLR4- and NLRP3-mediated signaling. Concomitantly, beneficial gut-derived metabolites (acetate, propionate, butyrate) decrease, while detrimental metabolites increase (e.g., TMAO), potentially fostering myocardial fibrosis, diastolic dysfunction, and adverse remodeling. SCFAs—acetate, propionate, and butyrate—may exert pleiotropic actions that directly target HFpEF pathophysiology: they may provide a CPT1-independent energy substrate to the failing myocardium, may improve lipid and glucose homeostasis via G protein-coupled receptors and AMPK activation, and may contribute to lower blood pressure and sympathetic tone, reinforce gut barrier integrity, and act as anti-inflammatory and epigenetic modulators through the inhibition of NF-κB, NLRP3, and histone deacetylases. This review summarizes current evidence linking gut microbiota dysfunction to cardiometabolic HFpEF, elucidates the mechanistic role of SCFAs, and discusses nutritional approaches aimed at enhancing their production and activity. Targeting gut–heart axis and SCFAs pathways may represent a biologically plausible and low-risk approach that could help attenuate inflammation and metabolic dysfunctions in patients with cardiometabolic HFpEF, offering novel potential therapeutic targets for their management. Full article

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder. It is estimated that AF affects over 52 million people worldwide, with its prevalence expected to double in the next four decades. AF significantly increases the risk of stroke and heart failure, contributing to 340,000 excess deaths annually. Beyond these life-threatening complications, AF results in limitations in physical, emotional, and social well-being causing significant reductions in quality of life and resulting in 8.4 million disability-adjusted life-years per year, highlighting the wide-ranging impact of AF on public health. Moreover, AF is increasingly recognized for its association with cognitive decline and dementia. AF is a chronic and progressive disease characterized by rapid and erratic electrical activity in the atria, often in association with structural changes in the heart tissue. AF is often initiated by triggered activity, often from ectopic foci in the pulmonary veins. These triggered impulses may initiate AF via: (1) sustained rapid firing with secondary disorganization into fibrillatory waves, or (2) by triggering micro re-entrant circuits around the pulmonary venous-LA junction and within the atrial body. In each instance, AF perpetuation necessitates the presence of a vulnerable atrial substrate, which perpetuates and stabilizes re-entrant circuits through a combination of slowed and heterogeneous conduction, as well as functional conduction abnormalities (e.g., fibrosis disrupting tissue integrity, and abnormalities in the intercalated disks disrupting effective cell-to-cell coupling). The re-entry wavelength, determined by conduction velocity and refractory period, is shortened by slowed conduction, favoring AF maintenance. One major factor contributing to these changes is the disruption of the extracellular matrix (ECM), which is induced by atrial fibrosis. Fibrosis-driven disruption of the ECM, especially in the heart and blood vessels, is commonly caused by conditions such as aging, hypertension, diabetes, smoking, and chronic inflammatory or autoimmune diseases. These factors lead to excessive collagen and protein deposition by activated fibroblasts (i.e., myofibroblasts), resulting in increased tissue stiffness, maladaptive remodeling, and impaired organ function. Fibrosis typically occurs when cardiac fibroblasts are activated to myofibroblasts, resulting in the deposition of excessive collagen and other proteins. This change in ECM interferes with the normal electrical function of the heart by creating irregular, fibrotic regions. AF and atrial fibrosis have a reciprocal relationship: AF promotes fibrosis through fibroblast activation and extracellular matrix buildup, while atrial fibrosis can sustain and perpetuate AF, contributing to higher rates of AF recurrence after treatments such as catheter ablation or cardioversion. Full article

Acetyl phosphate (AcP) is a microbial metabolite acting as a link between cell metabolism and signaling, providing the survival of bacteria in the host. AcP was also identified as an intermediate of pyruvate oxidation in mammalian mitochondria and was found in the human blood in some severe pathologies. The possible contribution of circulating AcP to the maintenance of the physiological or pathological states of the body has not been studied. Since AcP can function as a donor of phosphate groups, we have examined in vitro the influence of AcP on calcium signaling in mitochondria and cells by measuring the membrane potential and the calcium retention capacity of mitochondria by selective electrodes and by assaying the cell calcium signaling by Fura-2AM fluorescent radiometry. AcP was shown to induce a concentration-dependent increase in the mitochondrial resistance to calcium ion loading both in the control and in the presence of ADP. This effect was especially pronounced when mitochondria were incubated in a phosphate-free medium; under these conditions, AcP strongly raised the membrane potential and increased the rate of calcium uptake and the calcium retention capacity several times. Moreover, AcP induced similar changes in human cells when calcium signaling was activated by ATP, to a greater extent in neuroblastoma cells than in astrocytes. In the presence of AcP, a tendency for an increase in the amplitude and a decrease in the continuance of the ATP-induced calcium response was observed. These changes are probably associated with the activation of calcium buffering by mitochondria due to the delivery of phosphate during the hydrolysis of AcP. The results show that AcP is involved in the regulation of the Ca²⁺ balance in cells by activating the accumulation of calcium ions by mitochondria, especially under phosphate deficiency. A shift in calcium signaling mediated by AcP supplementation may be caused by hyperphosphatemia, which is now considered as one of basic contributors to cellular dysfunction and progression of various diseases, including sepsis. Full article

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Among the genetic risk factors linked to AD, the apolipoprotein E4 (ApoE4) remains the strongest. It is well known that carrying the ApoE4 isoform is associated with advanced AD pathology, blood–brain barrier (BBB) disruption, and changes in lipid metabolism. In this review, we provide an overview of the role of centrally and peripherally produced ApoE in AD. After this introduction, we focus on new findings regarding ApoE4’s effects on AD pathology and BBB function. We then discuss ApoE’s role in lipid metabolism in AD, highlighting examples of lipid changes caused by carrying the ApoE4 isoform. Next, the review explores the implications of ApoE4 isoforms for current treatments—whether they involve anti-amyloid therapy or other pharmacological agents used for AD—emphasizing the importance of personalized medicine approaches for patients with this high-risk allele. This review aims to provide an updated overview of ApoE4’s effects on AD pathology and treatment. By integrating recent discoveries, it underscores the critical need to consider ApoE4 status in both research and clinical settings to enhance therapeutic strategies and outcomes for individuals with AD. Full article

Background: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition influenced by both genetic and non-genetic factors, although the underlying pathomechanisms remain unclear. We systematically analyzed microRNA (miRNA) expression and associated functional pathways in ASD to evaluate their potential as prenatal/postnatal, diagnostic, and prognostic biomarkers. Methods: Peripheral blood mononuclear cells from 12 Sicilian patients with ASD (eight with normal cognitive function) and 15 healthy controls were analyzed using small RNA sequencing. Differential expression analysis was performed with DESeq2 (|fold change| ≥ 1.5; adjusted p ≤ 0.05). Functional enrichment and network analyses were conducted using Ingenuity Pathway Analysis, focusing on Diseases and Biofunctions. Results: 998 miRNAs were differentially expressed in ASD, 424 upregulated and 553 downregulated. Enriched pathways were primarily associated with psychological and neurological disorders. Network analysis highlighted three principal interaction clusters related to inflammation, cell survival and mechanotransduction, synaptic plasticity, and neuronal excitability. Four miRNAs (miR-296-3p, miR-27a, miR-146a-5p, and miR-29b-3p) emerged as key regulatory candidates. Conclusions: The marked divergence in miRNA expression between ASD and controls suggests distinct regulatory patterns, thus reinforcing the central involvement of inflammatory, autoimmune, and infectious mechanisms in ASD, mediated by miRNAs regulating S100 family genes, neuronal migration, and synaptic communication. However, rather than defining a predictive biomarker panel, this study identified candidate miRNAs and regulatory networks that may be relevant to ASD pathophysiology. As such, further validation in appropriately powered cohorts with predictive modeling frameworks are warranted before any biomarker or diagnostic implications can be inferred. Full article