Search Results (5,558)

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide, increasingly driven by metabolic dysfunction-associated steatotic liver disease alongside viral and alcohol-related cirrhosis. The tolerogenic immune environment of the liver enables tumor immune escape, with regulatory T cells (Tregs) playing a central role. This review synthesizes human-focused evidence (tissues, blood, clinical cohorts, and single-cell/spatial studies) through September 2025 to define how Tregs are recruited, maintained, and functionally deployed in HCC. Across datasets, intratumoral effector-like Tregs (eTregs) expressing ICOS, CTLA-4, CCR8, and CD39/CD73 accumulate within tumors and co-localize with exhausted cytotoxic PD-1^hi CD8⁺ T cells and suppressive myeloid cells. Recruitment is driven mainly by CCL20–CCR6 and CCL22/CCL17–CCR4 signaling, while CCR8 marks highly suppressive tumor-resident Tregs. Their persistence is supported by TGF-β, IL-10, IL-35, adenosine signaling, IL-2 sequestration, and metabolic adaptation. Spatial biomarkers, including ICOS⁺/CCR8⁺ eTreg density and CD8:Treg ratios, associate with prognosis and emerging immunotherapy responses. Etiology further shapes immune architecture: HBV-related HCC often forms Treg-exhausted T-cell niches around viral antigens, whereas MASLD/MASH promotes stromal and metabolic barriers that may reduce PD-(L)1 efficacy. Current treatments (PD-(L)1 blockade with anti-VEGF or CTLA-4, and some TKIs) intersect with Treg biology, while emerging strategies targeting CCR8, CCR4, ICOS, or the adenosine pathway aim to selectively disrupt intratumoral eTreg networks. This review underscores that an etiology-aware, spatial-biomarker framework may guide the integration of selective Treg targeting with PD-(L)1-based therapies in HCC. Full article

Background/Objectives: Childhood interstitial lung disease (chILD) represents a heterogeneous group of rare pulmonary disorders. Practical diagnostic approaches tested for feasibility and impact in comprehensive cohorts are lacking. We aimed to assess a simple etiologically focused classification approach, clarify the role of genetic testing and quantify the impact of non-pulmonary organ manifestations. Methods: We hypothesized that chILD can be classified in a clinically meaningful and versatile way by answering three questions: Which children have an etiological chILD diagnosis due to (1) identified (exposure-related) cause/lung injury, or (2) systemic disease? (3) In how many children without an etiological diagnosis can a genetic cause be identified? We also calculated the predictive value of non-pulmonary organ involvement for underlying systemic conditions. Results: Among 1693 patients, 24.7% were grouped as ILD related to exposure, 22.7% as ILD with systemic condition, 16.6% as ILD with genetic diagnosis of systemic disease, 10.0% as ILD with genetic diagnosis affecting the lungs only, and 25.8% as ILD without genetic diagnosis. The average genetic diagnostic yield was 50.8%, with higher rates in interstitial pneumonia (61.4%) or pulmonary alveolar proteinosis (87.1%). The presence of ≥two non-pulmonary organ manifestations increased the likelihood of an underlying systemic disease by three to five-fold. Conclusions: An etiological diagnostic strategy effectively classifies chILD and guides genetic testing. Exome or genome sequencing should be considered if ≥two non-pulmonary organs are involved or if the initial diagnosis becomes uncertain due to an unusual disease course or signs of a second underlying condition. Full article

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and KS-associated immune reconstitution inflammatory syndrome (IRIS-KS). Quantifying HHV-8 DNA in whole blood is clinically relevant, yet laboratory practices remain heterogeneous. Here, we developed and validated an in-house quantitative PCR (qPCR) assay targeting ORF26, optimized for whole blood. Assay calibration used plasmid, BCBL-1 cell–derived, and commercial HHV-8 DNA standards. Analytical validation was performed following the Clinical and Laboratory Standards Institute (CLSI) guidelines and the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines and showed a 95% limit of detection of 65.7 copies/reaction, efficiencies of 90–101% (R² > 0.99), and intra/inter-assay coefficients of variation < 6.5%. Strong correlations were observed among the three calibrators (R² > 0.97).Clinical validation against a composite reference yielded 100% sensitivity, specificity, PPV, and NPV. Viral loads (log₁₀ copies/mL) varied by clinical condition: classic KS and transplant-associated KS showed the lowest medians (2.30–2.23), MCD HIV− and PEL intermediate values (2.83–3.72), and epidemic KS, MCD HIV+, and IRIS-KS the highest (4.12, 4.86, and 5.03, respectively). Viremia > 5 log₁₀ copies/mL was associated with uncontrolled E-KS, MCD HIV+, and IRIS-KS. Longitudinal follow-up revealed viral load decline paralleled clinical improvement. This validated assay provides a robust, affordable tool for HHV-8 quantification in whole blood and supports its integration into diagnostic workflows and patient monitoring. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the aggregation of Lewy bodies, composed of the protein α-synuclein, and the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta. The management of PD seeks to mitigate motor symptoms by substituting diminished endogenous dopamine; nevertheless, it does not halt disease progression. Various animal models have been employed to elucidate the etiology of PD and to discover disease-modifying treatments. Zebrafish serve as a PD model owing to their capacity for high-throughput screening. This review presents updates on the currently available zebrafish models of PD, encompassing both chemically induced and genetically based models, and discusses their advantages and limitations. This review also delineates numerous investigative strategies that utilize the zebrafish PD model and summarizes the findings of previous studies. Taken together, further studies, including the investigation of the regeneration mechanism of DA neurons, neurobehavioral testing of adult zebrafish reflecting PD-associated neurocognitive impairment, and a reliable gene-based model providing precise gene knockout and reproducibility, may assist in elucidating the critical pathways that trigger PD and its progression, alongside potential targets to hinder this progression. Full article

Background: Hypoplastic left heart syndrome (HLHS) is defined as “a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch”. Without treatment, HLHS is usually lethal in the neonate. Many hypotheses have been advanced to explain the etiology of HLHS; however, no single theory appears to fully explain the phenotypic variability seen in HLHS. Furthermore, many of these theories offer no explanations regarding the precipitating events which lead to the development of HLHS. Objective: This review considers and critically evaluates the strengths and weaknesses of the leading theories proposed to explain the pathogenesis of HLHS—including hemodynamic disturbances, primary myocardial structural defects, valvar malformations, and genetic or epigenetic alterations that may provoke developmental and anatomic abnormalities. After presenting each model, we propose a novel, comprehensive, and data-driven framework which may assist researchers in developing models for the pathogenesis of the various subtypes of HLHS. Methods: Key findings from human fetal imaging, histopathology, genetic studies, and animal models were considered, as well as the hypothetical contribution of each in observed HLHS phenotypes. The rationales for these findings as causal factors initiating individual HLHS patterns, as well as how they might contribute to HLHS in general, were critically analyzed. Results: The flow theory is strongly supported by animal models and in utero interventions that demonstrate the impact of altered hemodynamics on cardiac morphogenesis. However, the flow theory fails to identify initial causes of disturbed flow or related histological features of HLHS like endocardial fibroelastosis. The myocardial and valve-first models suggest an important role in developmental defects, but do not necessarily have a strong experimental basis that provides explanations for how they mediate HLHS. Genetic studies in patients with HLHS have identified several candidate causal mutations. However, such genetic causes of HLHS exhibit incomplete phenotypic penetrance and clinical impact. A multifactorial framework attempts to integrate these diverse mechanisms and may provide the most coherent explanation that can accommodate the heterogeneity and variable presentation of HLHS. Such a framework may identify multiple forces that drive disease but does not provide useful pathways for future research about HLHS. Conclusions: No single hypothesis has fully explained how HLHS is initiated, progresses, and presents with the clinical conditions that are encountered by cardiac surgeons and cardiologists. The most current models suggest that the spectrum of HLHS reflects acomplex interaction between genetic susceptibility, flow-dependent cardiac remodeling, and environmental factors in utero. A multifactorial model integrates these diverse mechanisms and may provide the most coherent explanation for the various phenotypic variations in HLHS. Based on our analysis of the most current data and the strengths and weaknesses of the current theoretical frameworks, we propose a novel research strategy aimed at identifying specific cardiac progenitor cell populations whose dysregulation may represent a unifying explanation for the etiology of the various phenotypes of HLHS. Based on the arguments made throughout this manuscript that evaluate the various genetic, structural, and hemodynamic models of initiation of disease, we believe that the significant phenotypic variability across the spectrum of HLHS (i.e., the different anatomic subtypes for “classic” HLHS) most likely reflects different underlying etiologies and mechanisms. At the very least, it is very likely that the timing of the insult is critical in determining anatomic subtype. Based on the published data and the arguments within this manuscript, it seems naive to think that there is a single unifying mechanism explain all forms of HLHLS. Full article

Background and Objectives: Pulmonary hypertension (PH) remains associated with substantial mortality despite advances in treatment. Although prognostic factors have been widely described at sea level, their behavior in populations living at high altitude remains insufficiently characterized. This study aimed to identify factors associated with mortality during follow-up in patients with Group 1 PH residing at high altitude. Materials and Methods: A retrospective cohort study was conducted including patients with confirmed Group I PH diagnosed by right heart catheterization and treated between 2017 and 2022. Clinical, functional, and hemodynamic variables were analyzed. A penalized logistic regression model using Elastic Net methodology was applied to identify variables associated with five-year mortality. Results: A total of 165 patients were included, with a mean age of 41 years (SD 13.93), and 84.2% were women. Among PH etiologies, congenital heart disease was the most frequent cause (50.3%), followed by idiopathic PH (33.3%) and connective tissue disease-associated PH (12.7%). Five-year mortality was 13.3% (22/165). Idiopathic pulmonary hypertension was significantly more frequent among deceased patients compared to survivors (13/22 [59.1%] vs. 42/143 [29.4%], p = 0.025). Mortality was associated with acute pulmonary embolism, greater smoking burden, worse functional class, and adverse hemodynamic parameters. In multivariable analysis, acute pulmonary embolism (coefficient 0.196; OR 1.216; 95% CI 1.16–1.27; p < 0.001), ESC/ERS risk stratification (coefficient 0.158; OR 1.171; 95% CI 1.08–1.26; p < 0.001), pulmonary vascular resistance > 25 wood units (coefficient 0.180; OR 1.198; 95% CI 1.13–1.26; p < 0.001), and age ≥ 65 years (coefficient 0.171; OR 1.187; 95% CI 1.10–1.27; p < 0.001) were identified as risk factors, while female sex showed a protective effect (coefficient −1.041; OR 0.353; 95% CI 0.33–0.37; p < 0.001). Conclusions: In patients with Group 1 PH living at high altitude, several clinical, functional, and hemodynamic variables were associated with increased mortality, including acute pulmonary embolism, elevated pulmonary vascular resistance, advanced age, and intermediate-high risk stratification. Female sex was associated with lower mortality. Full article

Aluminum chloride (AlCl₃) is widely used in experimental toxicology, particularly in rodent models of neurodegeneration, where its effects have been studied primarily in the central nervous system. However, experimental findings also indicate that chronic exposure is associated with changes across multiple peripheral organs, although these observations are often considered separately. In this review, we bring together evidence from different organ systems to examine aluminum toxicity from a broader perspective. Rather than focusing on isolated tissue-specific effects, we consider the extent to which reported findings may reflect overlapping molecular disturbances expressed across physiological systems. Within this context, organ-level outcomes are discussed as potentially related manifestations of shared underlying processes, while acknowledging variability in experimental conditions and model interpretation. To structure this synthesis, we outline a conceptual framework that links recurring molecular responses, system-level regulatory influences, and tissue-specific patterns of injury. This approach is intended to provide a more integrated way of organizing existing data rather than to establish a single unifying mechanism. Importantly, the pathological alterations discussed throughout this review are interpreted as experimentally observed toxicological manifestations of chronic AlCl₃ exposure rather than evidence that aluminum constitutes a definitive etiological cause of Alzheimer’s disease. Overall, this review aims to complement existing neuro-focused interpretations of the AlCl₃ model by situating it within a multi-organ context and highlighting areas where further integrative investigation may be warranted. Full article

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The most common types—type 1 and type 2 diabetes—have different etiologies and pathophysiological mechanisms. Type 1 diabetes (T1DM) results from autoimmune destruction of the insulin-producing pancreatic β-cells, leading to the development of absolute insulin deficiency, whereas in type 2 diabetes (T2DM), impaired carbohydrate metabolism is primarily caused by insulin resistance and relative insulin deficiency. Current diagnostic criteria do not allow for the detection of the disease at the preclinical stage. MicroRNA (miRNA) influences post-translational regulation of gene expression by inhibiting mRNA translation and also promotes mRNA degradation. The aim of this review is to summarize current evidence on the role of microRNAs in the pathogenesis of T1DM and T2DM and to evaluate their potential as early diagnostic biomarkers and therapeutic targets. It is demonstrated that T1DM and T2DM exhibit altered expression of specific microRNAs involved in β-cell apoptosis, autoimmune inflammation, and insulin signaling. In T1DM, key miRNAs include miR-21, miR-25, miR-146a, and miR-375, which reflect β-cell destruction and the autoimmune process. In T2DM, critical roles are played by miR-9, miR-29, miR-34a, miR-103/107, miR-126, miR-143, and miR-375, which regulate insulin secretion, lipid metabolism, and tissue insulin sensitivity. Particular attention is given to microRNAs whose expression changes several years before clinical disease onset (miR-15a, miR-126, miR-375), offering opportunities for early diagnosis. Data are presented on circulating miRNAs in stable biological fluids (blood, urine). It should be emphasized, however, that the proposed microRNA panel currently represents only a potential diagnostic tool. This panel requires further validation and confirmation by clinicians in large-scale prospective studies and does not yet claim to be ready for routine clinical use. Nevertheless, the development of such a universal microRNA panel, followed by thorough clinical evaluation, has promising biomedical potential, which will not only allow for the diagnosis of diabetes at an early stage but also identify new therapeutic targets for personalized medicine. Full article

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease), represent a growing global health burden characterized by progressive neuronal loss and functional decline. Despite decades of intensive research, effective disease-modifying therapies remain limited, underscoring the urgent need for innovative therapeutic strategies. This review highlights recent advances in the understanding of disease etiology and emerging treatment approaches, with a particular focus on modalities with translational potential. We discussed novel disease-modifying interventions, including gene and cell therapies, RNA-targeting strategies, and immunotherapies aimed at clearing misfolded proteins such as amyloid-β, tau, and α-synuclein. In parallel, we examined the evolving recognition of neuroinflammation and mitochondrial dysfunction as actionable therapeutic targets, alongside progress in precision medicine and biomarker-guided approaches that enable early diagnosis and individualized treatment. Additionally, we summarized developments in repurposed pharmacological agents, neuroprotective compounds, and lifestyle interventions, emphasizing the importance of integrative, multimodal strategies. Across AD, PD, and ALS, convergent molecular mechanisms, including protein misfolding, oxidative stress, and disrupted proteostasis, present opportunities for cross-disease therapeutic targeting. Finally, we addressed key challenges and future directions, including translating preclinical efficacy into clinical success, optimizing CNS-targeted delivery systems, and navigating ethical considerations surrounding gene editing and stem cell therapies. Full article

Background/Objectives: Nutritional rickets is a childhood bone disorder leading to skeletal deformities and life-long disabilities. Early-stage diagnosis remains challenging due to the limited availability of non-invasive tools. This study explores metabolic variation associated with the active disease stages and with etiological factors, such as nutritional deficiencies and biochemical alterations. Methods: Untargeted ¹H NMR spectroscopy-based metabolomics were performed on urine and plasma samples collected from Bangladeshi children with radiologically active rickets (AR; n = 24; aged 2.98 ± 1.19 years), inactive rickets (IR; n = 36; aged 3.39 ± 1.87 years), and healthy matched controls (n = 58; aged 3.58 ± 1.59 years). This analysis also integrated corresponding clinical biochemistry and dietary intake data previously collected from the cohort. Results: Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) identified the 24 h urinary excretion of 13 metabolites to vary with AR, including those previously associated with bone metabolism such as β-aminoisobutyrate, N-methylnicotinamide, taurine and hypoxanthine. Biochemically, AR was strongly characterized by increased plasma alkaline phosphatase and decreased iFGF23. The multi-block integration of metabolomic, biochemical, and nutritional data achieved an 18.6% classification error rate. Children with IR exhibited metabolic profiles similar to healthy controls, aligning with their clinical resolution. Conclusions: Active nutritional rickets presents a distinct metabolic profile, highlighting novel biologically relevant metabolites. These exploratory signals provide insights into the physiological impact of the disease and warrant further targeted investigation to assess their potential for informing early non-invasive detection and preventive interventions. In the long term, such tools are vital to prevent irreversible skeletal damage and to help mitigate lifelong physical disability and the resulting social vulnerability for affected children. Full article

Moyamoya angiopathy (MMA) is a rare, chronic progressive cerebrovascular condition characterized by bilateral stenosis or occlusion of the terminal internal carotid arteries and their major branches. This progressive occlusion triggers the development of telangiectatic and fragile vessels at the base of the brain, creating the characteristic angiographic appearance of a “puff of smoke.” Depending on the etiology, MMA is classified as Moyamoya Disease (MMD) when idiopathic and primary or Moyamoya Syndrome (MMS) when associated with underlying systemic conditions. While the RNF213 gene, particularly the p.R4810K variant, is recognized as the major susceptibility locus for MMD in East Asian populations, it does not fully account for the global genetic landscape or the phenotypic diversity of the disease. This review provides a comprehensive overview of the genetic architecture of the entire MMA spectrum, exploring loci beyond RNF213. We analyze the role of genes involved in vascular smooth muscle cell contractility (ACTA2, MYH11), TGF-β signaling, and DNA repair mechanisms that drive MMS, alongside the genetic basis of syndromic forms associated with neurofibromatosis type 1, trisomy 21, and RASopathies. Understanding these diverse genetic drivers is crucial for early diagnosis, risk stratification, and the development of targeted molecular therapies. Full article

Background/Objectives: The evaluation of cognition is central to many neurological conditions, including traumatic brain injury, Alzheimer’s disease, Lewy body disease, frontotemporal degeneration, and vascular disorders. In clinical practice, particularly in aging populations, cognitive complaints often arise in the context of mixed neurological processes, requiring careful integration of cognitive and non-cognitive findings. Despite this, there remains limited clarity regarding the respective roles of neurologists and clinical neuropsychologists and the distinction between cognitive and neuropsychological assessments, terms that are often used interchangeably despite important differences in methodology and scope. This lack of a shared framework has practical consequences. Cognitive test results, when interpreted in isolation for diagnosis, may be misconstrued as comprehensive measures of brain function, particularly when non-cognitive neurological features such as motor, cerebellar, or vestibular abnormalities should have been considered (but were not). Methods: In this narrative review, we synthesize clinical guidelines, consensus statements, regulatory sources, and representative empirical literature to articulate a competence-based framework in which cognitive assessment is a medically integrated process incorporating history, functional evaluation, neurological examination, and the targeted use of standardized neuropsychological instruments. Results: Neurologists are trained to establish medical diagnoses and integrate cognitive findings into the context of neurological disease, while neuropsychologists contribute detailed psychometric characterization, culturally and demographically informed interpretation, cognitive phenotyping, functional characterization, and validity assessment in complex clinical and medicolegal contexts. Although neuropsychologists are qualified to diagnose neurocognitive disorders using standardized diagnostic criteria, attribution to specific neurological etiologies requires a comprehensive medical evaluation that extends beyond cognitive testing alone. Conclusions: We outline a tiered approach to evaluation that aligns assessment methods with clinical questions and supports accurate diagnosis, interdisciplinary collaboration, and patient-centered care. Full article

Schizophrenia is a chronic, progressive, and multifactorial disorder that leads to significant disability and social maladaptation in patients. Although considerable progress has been made in research, the etiology and pathogenesis of schizophrenia remain incompletely understood. However, the involvement of genetic factors in the development of this disease has been established. Using the GWAS catalog, we identified variants within the TCF4 gene that showed a significant association with schizophrenia. The GWAS catalog lists 30 variants within the TCF4 gene associated with schizophrenia. Among these, 12 variants demonstrate a specific association with schizophrenia in the absence of reported comorbidities. The presence and allele frequencies of these variants were subsequently analyzed in two population databases: Database of Population Frequencies of Genetic Variants in the Russian Federation (DPF) and gnomAD. For the functional annotation of the genetic variants, we utilized specialized tracks within the UCSC Genome Browser. The CpG Islands track served to identify potential regulatory regions. The GeneHancer database was used to predict SNP localization within enhancer regions and their potential target genes. To characterize the epigenetic landscape and functional chromatin states, the ENCODE Regulation and ENCODE cCREs tracks were utilized. Comparative analysis revealed significant heterogeneity in the allele and genotype frequencies of TCF4 polymorphisms between the Russian population and other global cohorts. This observed inter-ethnic variability may partly explain the discrepant genetic association findings for schizophrenia reported across different ancestral groups. Therefore, further functional studies are essential to define the precise mechanisms by which TCF4 variants contribute to disease pathogenesis. Full article

Background/Objectives: As a global chromatin organizer, SATB1 is increasingly implicated in neurodevelopmental disorders (NDDs). This study aims to delineate the clinical and molecular characteristics of a novel de novo SATB1 variant in a patient presenting with epilepsy-dominant NDDs phenotypes. Methods: Triggered by the onset of seizures, trio-based whole-exome sequencing (Trio-WES) was performed to identify the genetic etiology. Subsequent sleep electroencephalogram (EEG) and magnetic resonance imaging (MRI) were then conducted to further characterize the patient’s clinical phenotypes. Pathogenicity was assessed through structural modeling and functional characterization. Nonsense-mediated mRNA decay (NMD) status, protein expression profiles, and subcellular localization were determined by reverse-transcription quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. The transcriptional regulatory impacts of the variant were quantified using dual-luciferase reporter system targeting known downstream regulatory elements. Clinical responses to antiepileptic intervention was also monitored. Results: We identified a novel de novo heterozygous pathogenic frameshift variant in SATB1 (NM_002971.5: c.1718_1719insCA; p.Val574Argfs*134) in a patient presenting with early-onset epilepsy, mild intellectual developmental disorder (IDD), speech delay, and dental anomalies. Functional assays demonstrated that the variant-derived transcript escaping NMD, yielding a truncated protein that forms irregular punctate aggregates within nuclei. Dual-luciferase assays revealed significantly increased transcriptional activity, indicating a loss of the protein’s innate transcriptional regulatory capacity. Clinically, treatment with sodium valproate (VPA) successfully stabilized seizures of the patient, markedly reducing both frequency and intensity. Conclusions: The study reports a novel SATB1 frameshift variant that exerts pathogenicity significant functional impairment by disrupting protein localization and transcriptional regulation. These findings expand the genetic spectrum of SATB1-related NDDs and underscore the efficacy of targeted antiepileptic management in genetic diseases. Full article

Bovine mastitis is a major infectious disease in dairy cattle, causing significant economic losses and compromising animal health and milk quality worldwide. Among its etiological agents, Staphylococcus aureus is a key contagious pathogen due to its ability to establish persistent intramammary infections and evade host immune responses and antimicrobial therapy. This review summarizes current knowledge on the epidemiology, pathogenesis, clinical presentation, diagnosis, and control of S. aureus in bovine mastitis. Particular emphasis is placed on virulence mechanisms, including adhesion, intracellular persistence, biofilm formation, and immune evasion, which contribute to chronic and recurrent infections. The increasing prevalence of antimicrobial resistance, including methicillin-resistant and multidrug-resistant strains, is highlighted as a major challenge limiting treatment efficacy and posing risks within a One Health context. The review also discusses emerging alternative therapies and innovative control strategies, such as anti-biofilm approaches, immunomodulation, and improved diagnostics, aimed at reducing antimicrobial use. Advances in molecular and point-of-care diagnostic tools are considered for their role in early detection and targeted interventions. Overall, effective control of S. aureus mastitis requires integrated strategies combining prudent antimicrobial use, alternative therapies, improved hygiene, and a multidisciplinary One Health approach. Full article