Search Results (3,783)

Background: The aim of this study was to evaluate the diagnostic and prognostic performance of albumin-based inflammatory–nutritional indices in hyperemesis gravidarum (HG) and to determine their associations with disease severity and risk of re-hospitalization. Methods: This retrospective case–control study included 246 women with HG and 246 gestational-age-matched healthy pregnant controls at 6–16 weeks of gestation. Disease severity was classified as mild, moderate, or severe using the Pregnancy-Unique Quantification of Emesis (24 h scale) (PUQE-24) score. A comprehensive panel of albumin-based inflammatory indices—including C-reactive protein-to-albumin ratio (CAR), fibrinogen-to-albumin ratio (FAR), neutrophil-to-albumin ratio (NAR), leukocyte-to-albumin ratio (LAR), neutrophil percentage-to-albumin ratio (NPAR), monocyte-to-albumin ratio (MAR), hemoglobin–albumin–lymphocyte–platelet (HALP) score, modified HALP (m-HALP) score, prognostic nutritional index (PNI) score, systemic immune-inflammation index-to-albumin (SII/Alb), and systemic inflammatory response index-to-albumin (SIRI/Alb)—was calculated from routine complete blood count and serum biochemistry results obtained at diagnosis. Receiver operating characteristic analysis, along with univariate and multivariate logistic regression models, was performed to evaluate diagnostic performance and identify predictors of severe HG and re-hospitalization. Results: Albumin-based indices exhibited severity-associated alterations, with an overall trend toward worsening immuno-nutritional status across increasing HG severity. Among these, m-HALP score demonstrated the strongest inverse correlations with PUQE-24 score, ketonuria grade, length of hospital stay, and re-hospitalization risk (r = −0.74 to −0.52; all p < 0.001) and achieved the highest discriminative accuracy for both severe HG (AUC 0.864, 95% CI 0.836–0.892, p < 0.001) and re-hospitalization (AUC 0.722, 95% CI 0.675–0.766, p < 0.001). In multivariable analysis, higher HALP, m-HALP, and PNI were independently associated with a lower likelihood of severe HG. For re-hospitalization, higher m-HALP and HALP were independently associated with a lower risk, whereas higher NPAR, higher ketonuria grade, and higher PUQE-24 score were independently associated with an increased risk of re-hospitalization. Conclusions: Albumin-based indices, particularly m-HALP, demonstrated robust diagnostic and prognostic performance in HG compared with conventional biomarkers. These readily available, cost-neutral composite biomarkers enable objective severity stratification and accurate identification of patients at elevated risk of recurrent hospitalization, offering immediate potential to guide personalized, evidence-based clinical management. Full article

Dilated cardiomyopathy is characterized by progressive left ventricular dilation and impaired systolic function, with inflammation recognized as a key contributor to disease onset and adverse outcomes. C-reactive protein reflects systemic biochemical inflammation, whereas Delta Neutrophil Index represents the circulating immature neutrophil fraction and provides a cellular dimension of inflammatory burden. The combined diagnostic and prognostic value of these two biomarkers in dilated cardiomyopathy has not been adequately explored. This retrospective study included one hundred and fifty patients with dilated cardiomyopathy and one hundred and fifty age-, diabetes-, and hypertension-matched controls. Demographic, laboratory, and echocardiographic measurements were analyzed. The diagnostic and prognostic performances of C-reactive protein, Delta Neutrophil Index, and their combined model were assessed using logistic regression, receiver operating characteristic curve analysis, reclassification metrics, calibration testing, and decision curve analysis. Additional analyses were performed for patients with left ventricular ejection fraction below twenty percent, and mortality predictors were examined within the dilated cardiomyopathy cohort. Both C-reactive protein and Delta Neutrophil Index levels were significantly higher in patients with dilated cardiomyopathy than in controls and were further elevated in those with severely reduced ejection fraction. Delta Neutrophil Index remained independently associated with severe left ventricular dysfunction (ejection fraction ≤ 20%) in multivariable analysis (odds ratio 2.51). Each biomarker showed an independent association with the presence of dilated cardiomyopathy, and their combined model achieved the highest diagnostic accuracy. In receiver operating characteristic analysis, the area under the curve was 0.895 for Delta Neutrophil Index, 0.691 for C-reactive protein, and increased to 0.920 for the combined model, with a sensitivity of 81.3% and specificity of 92.0%. Delta Neutrophil Index was independently associated with severe left ventricular dysfunction and mortality, while C-reactive protein, age, ejection fraction, urea, and sodium also contributed to mortality risk. Delta Neutrophil Index was independently associated with mortality (odds ratio 2.51), while C-reactive protein, age, ejection fraction, urea, and sodium also contributed to mortality risk. The combined model provided significant improvement in risk reclassification and demonstrated superior calibration and greater net clinical benefit across a wide range of decision thresholds. C-reactive protein and Delta Neutrophil Index offer complementary diagnostic and prognostic information in dilated cardiomyopathy. Their combined use enhances diagnostic discrimination, strengthens risk stratification, and improves identification of patients at high risk for severe ventricular dysfunction and mortality. Incorporation of these accessible biomarkers into clinical evaluation may support earlier recognition and more tailored management of high-risk individuals. Full article

Background: Osteosarcoma (OSA) is the most common type of bone cancer in canines. Novel therapies are required to prevent the growth, survival, and metastatic progression of this cancer, to increase life expectancy of patients. Immunohistochemical (IHC) studies and RNA sequencing help us gain a deeper understanding into the molecular mechanisms of the disease. Methods: We previously compared canine OSA tissues with patient matched non-tumour tissues, revealing 442 overexpressed genes within the samples. The present research used IHC staining for four of these genes in OSA tissues: G protein-coupled receptor 64 (GPR64), TOX High Mobility Group Box Family Member 3 (TOX3), Matrix Metallopeptidase 12 (MMP-12), and Forkhead Box F1 (FOXF1). H-scoring was performed to quantitatively assess protein expression and qualitatively contextualise staining locations. Additional analyses addressed whether gender or anatomical location of lesions (axial or appendicular tumours) affected protein expression. cBioPortal was employed to analyse expression and genetic alterations in patients. Results: GPR64, TOX3, MMP-12, and FOXF1 showed high mRNA expression and genetic alterations in people with OSA. GPR64, TOX3, MMP-12, and FOXF1 were all expressed in canine OSA with novel findings regarding cellular expression. Additionally, differential sex expression was revealed for GPR64 and TOX3. Potential biomarkers or therapeutic targets were identified. Conclusions: These studies, and subsequent analysis, have provided insights into the molecular mechanisms associated with OSA progression and revealed potential biomarkers for diagnostic and prognostic purposes. A deeper understanding of genetic and protein interactions will support and progress novel pathways towards diagnostic, prognostic, and treatment interventions for OSA in both veterinary and human medicine. Full article

Paraneoplastic neurological syndromes (PNSs) are immune-mediated disorders caused by an antitumor response that cross-reacts with the nervous system, leading to severe and often irreversible neurological disability. Once considered exceedingly rare, PNSs are now increasingly recognized owing to the identification of novel neural autoantibodies, wider use of commercial testing, and the emergence of immune checkpoint inhibitor (ICI)-related neurotoxicity that phenotypically overlaps with classic PNS. In this narrative review, we performed a structured search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, without date restrictions, to summarize contemporary advances in the epidemiology, pathogenesis, diagnosis, and management of PNS. Population-based data show rising incidence, largely reflecting improved ascertainment and expanding indications for ICIs. Pathogenetically, we distinguish T-cell-mediated syndromes associated with intracellular antigens from antibody-mediated disorders targeting neuronal surface proteins, integrating emerging concepts of molecular mimicry, tumor genetics, and HLA-linked susceptibility. The 2021 PNS-Care criteria are also reviewed, which replace earlier “classical/non-classical” definitions with risk-stratified phenotypes and antibodies, and demonstrate superior diagnostic performance while underscoring that “probable” and “definite” PNS should be managed with equal urgency. Newly described antibodies and methodological innovations such as PhIP-Seq, neurofilament light chain, and liquid biopsy are highlighted, which refine tumor search strategies and longitudinal monitoring. Management principles emphasize early tumor control, prompt immunotherapy, and a growing repertoire of targeted agents, alongside specific considerations for ICI-associated neurological syndromes. Remaining challenges include diagnostic delays, limited high-level evidence, and the paucity of validated biomarkers of disease activity. Future work should prioritize prospective, biomarker-driven trials and multidisciplinary pathways to shorten time to diagnosis and improve long-term outcomes in patients with PNS. Full article

Background: Triple-negative breast cancer (TNBC), defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is associated with increased BRCA1/2 mutation rates. Extracellular vesicles (EVs) play a pivotal role in TNBC progression. This study aimed to analyze BRCA1/2 mutations and identify EV-related biomarkers for TNBC by employing TNBC-related datasets and EV-related genes (EVRGs). Methods: Initially, BRCA1/2 mutations in TNBC patients were examined. Differentially expressed EVRGs (DE-EVRGs) were identified by integrating the results of both differential expression analysis and weighted gene co-expression network analysis (WGCNA). Biomarkers were identified using Receiver Operating Characteristic (ROC) and Kaplan–Meier (K–M) analyses. Finally, functional enrichment, drug prediction, molecular docking, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses were performed. Results: Waterfall plots indicated that TP53 exhibited the highest mutation frequency in both the mutation (MUT) and wild-type (WT) group. Four distinct types of immune cells (for example, eosinophils and neutrophils) showed significantly elevated expression levels in the WT group. Notably, PLA2G5 was identified as a biomarker of TNBC and its expression was significantly lower in TNBC (p = 0.0025). Functional analysis demonstrated that PLA2G5 is enriched in the “drug metabolism cytochrome P450” pathway. Finally, 20 drugs targeting PLA2G5 were identified, among which leukotriene C4 demonstrated a binding affinity of −7.2 kcal/mol. This finding suggests that leukotriene C4 has potential therapeutic applications for the treatment of TNBC. Conclusions: Our study found significant differences between the MUT and WT groups, identifying PLA2G5 as a biomarker for TNBC and offering a theoretical basis for TNBC treatment. Full article

Background/Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to pose a significant global health challenge due to its high transmissibility and potential for severe clinical outcomes. Early identification of patients at risk of hospitalization is essential for effective triage in emergency departments and for the optimal allocation of healthcare resources. Methods: This prospective study included 84 patients aged over 18 years who presented to the emergency department on 23 December 2020, with suspected SARS-CoV-2 infection. Initially, 100 patients were evaluated, and 16 were excluded based on predefined exclusion criteria. The mean age of the participants was 53.65 ± 13.62 years, and 39 (46.4%) were women. Results: At admission, the mean signal peptide, CUB domain, EGF (SCUBE-1) level among SARS-CoV-2 patients was 0.16 ± 0.08 ng/mL. There was no significant difference in SCUBE-1 levels between patient and control groups (n = 59 vs. 25), but levels differed significantly between hospitalized and home-treated patients (n = 37 vs. 22; p = 0.001). Neutrophil count (p = 0.001) and NLR (p = 0.010) were higher in patients than controls and also higher in hospitalized than home-treated patients (p = 0.003 and p = 0.015). ROC analysis revealed that SCUBE-1 predicted hospitalization with 84.6% sensitivity and 88.9% specificity. A positive correlation was observed between SCUBE-1 levels and length of hospital stay (p = 0.007, r = 0.554), with a median stay of 9.0 (5.0–11.0) days. Conclusions: SCUBE-1 levels were significantly associated with disease severity in SARS-CoV-2 patients and may serve as a promising biomarker to support clinical decision-making for hospitalization versus home-based management. Full article

Background: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by repetitive behaviors and social interaction deficits. While the severity of ASD is classified into levels (1–3) by the DSM-5, reliable circulating biomarkers to differentiate these levels are lacking. This retrospective pilot study examines plasma amino acid levels in children with ASD to identify the potential biomarkers of disease severity. Methods: Plasma samples from 30 children diagnosed with ASD (24 males, 6 females, aged 3–12 years) were analyzed. Participants were stratified into two groups based on the Autism Diagnostic Observation Schedule Calibrated Severity Score (ADOS CSS): Group 1, presenting with mild symptoms (Level 1, n = 11), and Group 2, characterized by moderate-to-severe symptoms (Levels 2–3, n = 19). This was further confirmed by the identification of electroencephalogram (EEG) anomalies (21.1%) and magnetic resonance imaging (MRI) abnormalities (5.3%), which were detected exclusively in Group 2 and absent in Group 1. Amino acid levels were measured by ion-exchange chromatography. Statistical analyses (Mann–Whitney U test and chi-square test) were used to compare AA levels between groups. Results: Statistically significant differences were observed in the levels of phosphoethanolamine, aspartic acid, and glutamic acid between the two groups. These amino acids (AA) were significantly higher in the moderate-to-severe symptoms group (Levels 2–3) compared to the mild symptoms group (Level 1) (p < 0.05). All AA values remained within age-appropriate reference ranges. Conclusions: Plasma levels of phosphoethanolamine, aspartic acid, and glutamic acid may serve as potential biomarkers for ASD severity in children. Results from this exploratory analysis suggest that AA profiling could differentiate ASD severity and identify specific metabolic pathways, such as excitatory neurotransmission and phospholipid turnover. Further studies with larger cohorts are necessary to validate these findings and explore the role of AAs in ASD pathophysiology. Full article

Background/Objectives: Schizophrenia (SCH) and bipolar disorder (BD) share overlapping symptoms and genetic factors, making differential diagnosis challenging and often leading to misdiagnosis. This study aimed to identify potential lipid biomarkers of serum capable of distinguishing BD from SCH. Methods: Lipid profiles of serum from 30 SCH and 31 BD patients were analyzed in triplicates using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). Chemometric analysis was applied, including class and gender identifiers. Orthogonal partial least squares (OPLS) models with 1000 cross-validations were used to validate feature subsets. Results: The chemometric analysis included the most relevant metabolites in the comparison between all samples of SCH and BD patients, identifying five key biomarkers (LPC 16:0, SM 33:1, SM 32:1, compound C30H58O3, and PC 30:0) with VIP scores > 1 for distinguishing BD from SCH. Gender-specific models revealed five biomarkers in males (SM 32:1, SM 33:1, PC 32:1, PC 30:0, and FA 16:1) and two in females (LPC 16:0 and C30H58O3). These biomarkers primarily belonged to glycerophospholipids (GPs) and sphingophospholipids (SPs). Conclusions: Comparative lipid profiling between SCH and BD, including gender-specific subgroups, enabled identification of potential diagnosis-specific biomarkers. Elevated levels of GPs and SPs in SCH patients suggest lipid metabolism differences that may support improved diagnostic accuracy and personalized treatment strategies. Full article

Metal–organic framework (MOF)-based surface-enhanced Raman scattering (SERS) sensors have emerged as a versatile platform for high-sensitivity and selective detection in agricultural, environmental, and biomedical applications. By integrating plasmonic nanostructures with tunable MOF architectures, these hybrid systems combine ultrahigh signal enhancement with molecular recognition, analyte preconcentration, and controlled hotspot distribution. This review provides a comprehensive overview of the fundamental principles underpinning MOF–SERS performance, including EM and chemical enhancement mechanisms, and highlights strategies for substrate design, such as metal–MOF composites, plasmon-free frameworks, ligand functionalization, and hierarchical or core–shell architectures. We further examine their applications in environmental monitoring, pesticide and contaminant detection, pathogen identification, biomarker analysis, and theranostics, emphasizing real-sample performance, molecular selectivity, and emerging integration with portable Raman devices and AI-assisted data analysis. Despite notable advances, challenges remain in reproducibility, quantitative reliability, matrix interference, scalability, and biocompatibility. Future developments are likely to focus on rational MOF design, sustainable fabrication, intelligent spectral interpretation, and multifunctional integration to enable robust, field-deployable sensors. Overall, MOF-based SERS platforms represent a promising next-generation analytical tool poised to bridge laboratory innovation and practical, real-world applications. Full article

Background: Diabetic peripheral neuropathy (DPN) is a major complication of type 2 diabetes mellitus (T2D) that reduces quality of life and increases the risk of foot ulcers and amputations. Early detection is essential, and blood-based biomarkers may support improved screening and timely intervention. This study aimed to identify novel circulating biomarkers for the identification of DPN in patients with T2D. Methods: In the screening phase, plasma samples from 43 participants (10 healthy volunteers [HV], 20 T2D without complications, and 13 T2D with DPN) were analyzed using an antibody array targeting 310 proteins. Thirteen differentially expressed proteins were identified, and six hub proteins were selected through bioinformatic analysis. In the validation phase, plasma concentrations of the six proteins were measured by ELISA in 252 subjects (100 HV, 97 T2D without complications, and 55 T2D with DPN). Mucin-1 expression in sciatic nerves was further evaluated in db/db mice. Results: Of the six hub proteins (TGFB1, MUC1, PF4, IL2RA, SELL, B2M), only mucin-1 showed a significant increase in the DPN group. Plasma mucin-1 positively correlated with MNSI scores and negatively with motor and sensory nerve conduction velocities. In db/db mice, sciatic nerve mucin-1 expression was elevated, while CD31 expression was reduced. Conclusions: Plasma mucin-1 is strongly associated with DPN in both humans and animals and may serve as a promising biomarker for the screening and early identification of DPN. Full article

Synthetic cannabinoids (SCs) are a rapidly developing kind of novel psychoactive substance, frequently associated with acute intoxication and public health concerns. This study aimed to elucidate and compare the phase I metabolic pathways of two structurally related SCs, 5F-ADB-PINACA and 5F-ADBICA, using in vitro and in vivo models. Temporal metabolic profiling was performed to identify potential signature metabolites. Temporal abundance patterns and correlation cluster analysis of metabolites were analyzed to determine metabolite biomarkers. The two SCs were incubated with pooled human liver microsomes for 24 h and were also evaluated in vivo in zebrafish. Metabolite profiles were characterized using UHPLC-QE Orbitrap-MS. HLM analysis identified 21 5F-ADB-PINACA metabolites and 28 5F-ADBICA metabolites. Metabolites of 5F-ADBICA were detected for the first time in vitro and in a zebrafish model. Zebrafish studies confirmed the presence of all key metabolites observed in HLM. Comparative analysis of their metabolic pathways revealed differences in metabolism driven by structural differences between the indazole and indole cores. This is the first time that correlation analysis has been used in the temporal metabolic profiling of SCs. This study comprehensively characterized the metabolism of 5F-ADB-PINACA and 5F-ADBICA, identifying M13 (hydrolytic defluorination) as a potential metabolite biomarker for 5F-ADB-PINACA and M19 (hydrolytic defluorination) as a potential metabolite biomarker for 5F-ADBICA. The metabolic reactions of the main metabolites of the two synthetic cannabinoids are consistent. However, their metabolic processes (i.e., the overall metabolic pathways and temporal progression of these reactions) are different, which illustrates the metabolic similarity of structurally similar synthetic cannabinoids and the impact of different structures on the metabolic processes. Full article

Introduction: A group of approximately 15 Candida species are frequently found to be responsible for human invasive candidiasis, an infection that appears in patients with prolonged hospitalization, particularly in Intensive Care Units, and in immunosuppressed individuals. Given the considerable burden if not rapidly treated, clinicians face diagnostic challenges in distinguishing infection. The objective of this narrative review is to summarize the clinically applicable biomarkers used for invasive candidiasis and to evaluate their performance and create a diagnostic algorithm for clinical practice. Methods: This narrative review was conducted by searching PubMed and Scopus for studies published between 1990 and 2025, using keywords related to invasive candidiasis and non-culture diagnostic biomarkers. Clinical guidelines and consensus documents from major infectious diseases societies were additionally reviewed to supplement. Results: Blood cultures, which are considered the “gold standard” for diagnosis, face important fallouts caused by the limited sensitivity of 50%. Polymerase Chain Reaction assays can identify Candida species at an early stage when compared to blood cultures, demonstrating high specificity that ranges between 91% and 98, due to their high cost, and the limitations regarding only the identification of certain species, their widespread use remains limited. Non-culture serological tests such as mannan, anti-mannan and 1-3-β-D-glucan can detect fungal cell wall components or antibodies directed towards them. These tests have the advantage of being performed directly from blood samples. Reported sensitivity and specificity are 83% and 86% for mannan/anti-mannan, and 73% and 80% for 1-3-β-D-glucan, respectively. They are used for early detection of candidemia in high-risk patients, including immunocompromised individuals. Conclusions: Our report suggests that the traditional “gold standard” for diagnosing invasive candidiasis can be improved by integrating and combining novel biomarkers in the diagnostic pathways, and, thus, potentially reducing the time spent for diagnosing and facilitating early treatment access. Full article

Background: Device-detected subclinical atrial fibrillation (SCAF) and atrial high-rate episodes (AHRE) are increasingly recognized in patients with cardiac implantable electronic devices and through long-term rhythm monitoring. Although often asymptomatic, these episodes are associated with a higher risk of clinical atrial fibrillation (AF), stroke, and heart failure. Aims: This narrative review summarizes clinical, electrocardiographic, echocardiographic, and circulating biomarkers associated with the development and progression of device-detected SCAF/AHRE. Methods: We performed a comprehensive search of PubMed, Embase, and Scopus using combinations of the terms “subclinical atrial fibrillation”, “atrial high-rate episodes”, “device-detected AF”, “predictive factors”, “P-wave morphology”, “echocardiographic parameters”, “left atrial strain”, and “biological markers”. We included English-language-only studies of patients with cardiac implantable electronic devices or long-term monitoring and reporting incident SCAF/AHRE or AF as outcomes, published in the last 10 years. Results: Older age, high body mass index, heart failure, obstructive sleep apnea, and C₂HEST score are consistently associated with SCAF. On-surface electrocardiogram (ECG) and device electrograms, prolonged and dispersed P-wave indices, low atrial sensing amplitude, and specific pacing configurations, particularly right ventricular apical pacing with wide QRS, predict incident and longer-lasting AHRE. Echocardiographic markers of atrial cardiomyopathy, including increased left atrial volume and impaired atrial strain, together with indices of left ventricular diastolic dysfunction, further refine risk. Among circulating biomarkers, galectin-3 and high-sensitivity C-reactive protein show the most reproducible associations with incident AHRE. Conclusions: A multiparametric approach combining clinical profile, ECG features, advanced echocardiography, and selected biomarkers may improve identification of patients at risk for device-detected SCAF. Further prospective studies are needed to define risk thresholds that justify intensified rhythm surveillance and early initiation of anticoagulation or rhythm control strategies, especially in AHRE shorter than 24 h. Full article

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, caused by an abnormal expansion of CAG repeats at the ATXN7 gene. Disease onset and progression vary among patients, underscoring the need for novel tools to improve disease monitoring. Circulating miRNAs represent a promising prognostic tool, due to their minimally invasive sampling and high stability. The aim of this study was to assess the expression of twelve circulating miRNAs associated with neurodegeneration in plasma samples from SCA7 patients and in an inducible SCA7 glial cell model. A comparison of SCA7 patients and controls revealed that nine miRNAs exhibited significantly higher expression. Furthermore, comparison of patients with different SCA7 phenotypes to controls revealed that most miRNAs were overexpressed in plasma from early-onset patients corresponding to the clinically more severe phenotype. Regarding the cell model, we identified three miRNAs that were dysregulated; however, only hsa-miR-342-5p displayed a pattern consistent with that observed in the plasma of patient. Our findings indicate that hsa-miR-342-5p is differentially expressed in the plasma of patients and the SCA7 cellular model, implying that it can serve as a biomarker and facilitate the identification of novel processes involved in SCA7. Full article

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia worldwide and is now increasingly regarded as a disease of chronic inflammation and progressive atrial fibrosis. Understanding of molecular mechanisms that mediate the linkage between systemic metabolic dysregulation, inflammation, and structural atrial changes is crucial for informing risk stratification and targeting of prevention strategies. This review provides evidence from 105 studies focusing on the contributions of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), galectin-3, and galectin-1 to cardiac fibrogenesis, atrial fibrosis, and AF pathogenesis. We also link metabolic syndrome to these biomarkers and to atrial remodeling, as well as echocardiographic correlates of fibrosis. TGF-β1 is established as the central profibrotic cytokine and promotes Smad-based fibroblast activation, collagen accumulation, and structural atrial remodeling. Its role is highly potentiated by thrombospondin-1 by turning latent TGF-β1 into its potent form. TNF-α and IL-6 also play an integral role in the inflammatory fibrotic continuum by activating NF-κB and STAT3 signaling, promoting fibroblast proliferation, electrical uncoupling, and extracellular matrix accumulation. Galectin-3 is a potent profibrotic mediator that promotes TGF-β signaling and is a risk factor for negative outcomes, whereas Gal-1 seems to regulate inflammation resolution and may exert context-dependent protective or maladaptive roles. Metabolic syndrome is strongly associated with excessive levels of these biomarkers, chronic low-grade inflammation, oxidative stress, and ventricular and atrial fibrosis. Chronic clinical findings show that metabolic syndrome (MetS) increases AF risk, exacerbates atrial dilatation, and is associated with worse postoperative outcomes. Echocardiographic data are connected to circulating biomarkers and are non-invasive for evaluating atrial remodeling. The evidence to date supports that atrial fibrosis should be considered an end point of systemic inflammation, metabolic dysfunction, and activation of profibrotic molecular pathways. Metabolic syndrome, due to its chronic low-grade inflammatory environment and prolonged levels of metabolic stress, manifests as an important upstream factor of fibrotic remodeling, which continuously promotes the release of cytokines, oxidative stress, and fibroblast activation. Circulating fibrotic biomarkers, in comparison with metabolic syndrome, serve separate yet interdependent pathways that help orchestrate atrial structural remodeling through the simultaneous process but can also provide a long-term indirect measure of ongoing profibrotic activity. The integration of these biomarkers with superior atrial imaging enables a broader understanding of the fibrotic substrate of atrial fibrillation. This combined molecular imaging approach can facilitate risk stratification, refine therapeutic decisions, and facilitate early identification of higher-risk metabolic phenotypes, thus potentially facilitating directed antifibrotic and anti-inflammatory therapy in atrial fibrillation. Full article