Search Results (6,931)

Background: Long COVID is a heterogeneous post-viral condition in which persistent neurological, autonomic, cognitive, and psychometric symptoms often occur without clear isolated biomarker abnormalities. This mismatch suggests that disease persistence may be driven not only by changes in individual markers, but by longitudinal reorganization of biological and clinical interactions. Materials and Methods: This observational longitudinal study evaluated patients with persistent symptoms after confirmed SARS-CoV-2 infection at 3 and 6 months. Clinical assessment included neurological examination, Hospital Anxiety and Depression Scale, Beck Depression Inventory, and COMPASS-31. Biomarkers representing hypoxia signaling, oxidative/redox stress, endothelial and renin–angiotensin system activity, glycation-related processes, and complement regulation were analyzed. Correlation analysis, association-level biomarker–clinical network modeling, and complementary Graphical LASSO-based sparse network estimation were used to compare network density, community organization, centrality, and edge rewiring between time points. Results: Conventional paired analysis identified HIF-1$\alpha$ as the only continuous variable with a statistically significant longitudinal change (Wilcoxon statistic = 610.0, $p=0.000350$), whereas association-level network analysis revealed a broader systems-level signal. The association-level biomarker–clinical network preserved a similar global size at 3 and 6 months, with 16 nodes, 27 versus 26 edges, and densities of 0.225 versus 0.217. However, this apparent stability concealed substantial rewiring: 19 edges were shared, 8 were lost, and 7 emerged. Complementary Graphical LASSO analysis with 1000 bootstrap resamples supported this pattern by identifying a conservative sparse conditional-dependency core, including seven shared conditional-dependency edges across time points and selective weakening of four early conditional dependencies. The C3–C4 relationship reversed from negative to positive correlation ($r=-0.618$ to $r=0.618$), indicating marked remodeling of complement-associated regulation. A psychometric–autonomic module involving Beck, HADS I, HADS II, and COMPASS-31 remained stable across both assessments. Conclusions: Long COVID progression was characterized by dynamic remodeling of immune, endothelial/RAS, oxidative-redox, hypoxia-related, autonomic, and psychometric interactions. Longitudinal network analysis identified a systems-level interaction structure that was not captured by isolated biomarker comparisons alone and that was further supported by complementary sparse conditional-dependency analysis. Full article

Bovine Mycoplasma bovis pneumonia (MBP) is an important component of bovine respiratory disease, and its management is complicated by persistent infection and antimicrobial stewardship concerns. Houttuynia cordata Thunb. has reported anti-inflammatory and immunomodulatory activities, but its potential host-directed mechanisms in MBP remain unclear. This in silico study used network pharmacology and molecular docking to identify candidate compounds, common drug–disease targets, enriched biological functions, and predicted ligand–target interactions. A total of 145 putative targets of H. cordata and 474 MBP-associated disease targets were obtained from TCMSP, GeneCards, OMIM, and CTD, yielding 43 common drug–disease targets. Dual-confidence STRING analysis, cytoHubba ranking, and MCODE module analysis prioritized TNF, IL6, IL1B, PTGS2, PPARG, IFNG, CASP3, and MMP9 as candidate core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated convergence on cytokine-mediated signaling, inflammatory response, immune regulation, oxidative stress, IL-17 signaling, and TNF signaling. Molecular docking suggested favorable predicted interactions for quercitrin–PTGS2, quercetin–TNF, quercetin–IL6, and quercitrin–CASP3. These computational findings suggest that H. cordata may be associated with host inflammatory and immune-response modulation in MBP, mainly through flavonoid-related interactions with inflammation- and apoptosis-related targets. Further bovine-specific experimental validation is required before biological activity or practical application can be inferred. Full article

Systemic sclerosis (SSc) is a severe autoimmune rheumatic disease with high mortality. Epigenetic factors, particularly micro-RNAs (miRNAs), may contribute to its pathogenesis by regulating gene expression. In this cross-sectional study, we assessed altered miRNA–mRNA regulatory networks in SSc and associated them with disease-related biological processes. We analyzed the miRNA profiles and differentially expressed genes (DEGs) of peripheral blood mononuclear cells (PBMCs) from 52 SSc patients (42 women and 10 men; mean age: 59.1 years) and 24 age- and gender-matched healthy controls. Total RNA was isolated and subjected to high-throughput next-generation sequencing for both miRNA and mRNA profiling. We identified 58 differentially expressed miRNAs (DEMs), 33 upregulated and 25 downregulated in SSc. In parallel, 6610 DEGs were detected (Mann–Whitney U-test, p < 0.05); 31 remained upregulated and nine downregulated after false discovery rate (FDR) correction. Integration of miRNA and mRNA data revealed 180 validated inverse miRNA–mRNA interactions. Notably, 22 of 31 upregulated DEGs corresponded to targets of downregulated miRNAs, indicating coordinated derepression. Functional enrichment analyses highlighted pathways related to extracellular matrix (ECM) remodeling, immune responses, fibrosis, and transcriptional regulation. Our findings suggest that altered miRNA expression contributes to widespread transcriptional dysregulation in SSc, promoting pro-fibrotic and immune-activated molecular pathways through coordinated miRNA–mRNA interactions. Full article

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are associated with immune-related adverse events (irAEs) and variable clinical outcomes. Clinical predictors of organ-specific irAEs remain indeterminate, particularly in real-world populations. Methods: We conducted a retrospective single-center cohort study including 751 adult patients with solid tumors treated with ICIs between 2018 and 2025. Clinical, demographic, and treatment-related variables were analyzed. Multivariable logistic regression identified predictors of irAEs, while associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed using logistic and Cox regression models. Results: The most frequent irAEs were endocrine (9.9%), dermatologic (9.1%), gastrointestinal (7.6%), and pulmonary (4.7%). Female sex independently predicted endocrine (aOR 1.98, p = 0.007) and rheumatologic irAEs (aOR 4.06, p = 0.007). Combination immunotherapy was associated with increased dermatologic (aOR 2.66, p = 0.013) and gastrointestinal irAEs (aOR 2.65, p = 0.016), while concurrent radiotherapy predicted gastrointestinal toxicity (aOR 1.82, p = 0.044). Atezolizumab was associated with higher pulmonary irAE risk (aOR 2.97, p = 0.048). Endocrine, dermatologic, gastrointestinal, and pulmonary irAEs were independently associated with improved ORR (OR range: 2.53–4.30, all p < 0.01). Conclusions: Organ-specific irAEs exhibit distinct clinical predictors and differential prognostic implications in patients receiving ICIs. Select irAEs are associated with improved treatment response and disease control, yet our results should be regarded as hypothesis-generating requiring further investigation. Full article

Diabetes mellitus comprises a group of heterogeneous metabolic disorders characterized by persistent hyperglycemia, progressive β-cell dysfunction, and multi-organ complications. Although type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have distinct pathogenic origins, both involve immune dysregulation, tissue stress, release of danger signals, and chronic inflammation. Dendritic cells (DCs), as antigen-presenting cells, integrate innate immune sensing, antigen presentation, cytokine production, T-cell regulation, and peripheral immune tolerance, placing them at a critical interface between autoimmunity and metabolic inflammation. In T1DM, DCs contribute to β-cell autoantigen presentation, tolerance breakdown, autoreactive T-cell activation, and insulitis amplification. In T2DM, DCs may contribute to adipose tissue inflammation, hepatic immunometabolic crosstalk, β-cell stress, vascular inflammation, and immune remodeling associated with diabetes-related complications. Here, we review the disease-specific roles of DC subsets in T1DM and T2DM and discuss shared molecular mechanisms, including pattern-recognition receptor signaling, metabolic reprogramming, inflammasome activation, cytokine networks, and the shift from immune tolerance to inflammation. We also evaluate therapeutic DC reprogramming strategies and their potential implications for targeted immunometabolic intervention in diabetes. Full article

Allergic diseases are increasing globally, particularly among children, who are highly vulnerable due to critical windows of immune development. This review examines climate change as a key environmental determinant driving the rising burden of pediatric allergic diseases, including asthma, allergic rhinitis (AR), atopic dermatitis (AD), and food allergy (FA). Climate change influences disease risk through interconnected pathways, such as increased air pollution, altered aeroallergen patterns, and more frequent extreme weather events. Elevated carbon dioxide (CO₂) levels and rising temperatures prolong pollen seasons and enhance allergenicity, while pollutants such as ozone (O₃) and particulate matter (PM) exacerbate airway inflammation and immune dysregulation. Emerging evidence emphasizes the role of early-life exposure, particularly during prenatal and early postnatal periods, when environmental insults can induce long-term effects via epigenetic modifications and immune reprogramming. These mechanisms may increase susceptibility to allergic sensitization and subsequent disease development. Epidemiological studies consistently link exposure to air pollution, including PM_2.5 (PM with aerodynamic diameter < 2.5 μm) and nitrogen dioxide (NO₂), with increased risk of allergic diseases in children. Additionally, climate change-related events such as wildfires, sand and dust storms, and thunderstorms further elevate exposure to allergens and pollutants, contributing to acute exacerbations and disease progression. Climate change may also contribute to allergic diseases through microbiome dysbiosis, as altered environmental microbial exposures, biodiversity loss, air pollution, and antibiotic-associated microbial disruption may impair immune tolerance and promote allergic sensitization in children. Addressing this growing public health challenge requires integrated mitigation strategies to reduce greenhouse gas (GHG) emissions and improve air quality, alongside adaptive interventions to enhance resilience and reduce exposure. Understanding these mechanisms is essential for developing targeted prevention strategies and protecting child health in a changing climate. Full article

Aging is accompanied by complex structural and functional immune system changes driven by genomic instability, epigenetic alterations, mitochondrial dysfunction, telomere attrition, loss of proteostasis, deregulated nutrient sensing, and the accumulation of senescent cells exhibiting a senescence-associated secretory phenotype, which altogether lead to severe consequences including altered antimicrobial defense, the overproduction of autoantibodies, and chronic, low-grade inflammation (inflammaging). In this article, we summarize age-related alterations in the function of primary and secondary lymphoid organs, including the bone marrow, thymus, spleen, and lymph nodes. The involution of these organs leads to impaired hematopoiesis, reduced production of naïve lymphocytes, and immune microenvironment disruption. We also describe aging-related impairment of the activity of neutrophils, macrophages, dendritic cells and natural killer cells, as well as dysregulation of T and B lymphocyte responses. Specifically, these alterations include a decline in naïve cell populations, an accumulation of memory and exhausted cells, and a reduction in the diversity of antigen receptors. Consequently, older individuals exhibit increased susceptibility to infections, cancer, and autoimmune diseases, along with diminished vaccine efficacy. Understanding the mechanisms underlying immune aging could lay the foundation for developing therapeutic strategies and lifestyle interventions to mitigate the adverse effects of this unfavorable process. Full article

Background: KRAS mutations are among the most common oncogenic drivers in non-small cell lung cancer (NSCLC) and are associated with substantial molecular and immunological heterogeneity. However, the clinicopathological associations and prognostic relevance of KRAS mutation subtypes and co-occurring genomic alterations in relation to PD-L1 expression and survival outcomes remain incompletely understood, particularly in the immunotherapy era. Methods: This retrospective single-center study included 93 KRAS-mutant NSCLC patients identified among 543 consecutively sequenced cases between March 2024 and March 2025. KRAS mutation subtypes, co-mutations involving TP53, STK11, and KEAP1, PD-L1 expression status, clinicopathological features, and survival outcomes were evaluated. Overall survival was assessed using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: KRAS mutations were detected in 17.1% of NSCLC patients. G12C was the most frequent KRAS subtype (38.7%), followed by G12V (18.3%) and G12D (14.0%). Co-occurring mutations were identified in 73.1% of cases, most commonly involving TP53 (40.9%) and STK11 (33.3%). PD-L1 expression was negative in 48.4% of patients, low in 28.0%, and high in 23.7%. No significant association was identified between KRAS mutation subtype and PD-L1 expression (p = 0.663). STK11-mutated tumors demonstrated a trend toward lower PD-L1 expression levels compared with STK11 wild-type tumors. However, none of the molecular variables retained independent prognostic significance. Immunotherapy was associated with significantly prolonged overall survival (median OS: 24 vs. 7 months, p = 0.013) and remained independently associated with improved survival in multivariate analysis (HR: 0.376, 95% CI: 0.204–0.694, p = 0.002). Advanced-stage disease independently predicted worse survival outcomes (HR: 13.43, 95% CI: 1.81–99.79, p = 0.011). Conclusions: KRAS mutation subtypes and co-occurring genomic alterations demonstrated limited independent prognostic significance in this real-world NSCLC cohort. In contrast, immunotherapy was associated with improved overall survival in this retrospective cohort. These findings should be interpreted as observational and hypothesis-generating rather than evidence of predictive treatment benefit. Larger prospective studies integrating genomic and immune biomarkers are warranted. Full article

Background/Objectives: Parkinson’s disease (PD) exhibits marked sexual dimorphism, with a higher incidence and earlier onset in men than in women. However, the impact of biological sex on systemic molecular alterations in PD remains poorly understood. This pilot study aimed to identify sex-specific circulating signatures associated with PD. Methods: Serum samples from a selected cohort of PD patients and healthy controls (HC) of both sexes were analyzed using an integrated biochemical and ¹H NMR-based metabolomic approach. Oxidative stress markers, antioxidant proteins, inflammatory mediators, matrix metalloproteinases, α-synuclein species, and circulating antibodies were evaluated. Results: This analysis indicated that, while global oxidative stress markers were unchanged, sex-related differences in antioxidant pathways were observed as suggested by the reduced Nrf2 expression observed in PD females and increased IL-6 levels, above all in male PD patients. MMP3 levels were significantly higher in female PD patients compared with males. Male patients showed higher levels of 52 kDa protease-resistant α-synuclein species, while females exhibited increased antibody titers against both monomeric and aggregated forms. Metabolomic profiling suggested a disease-associated metabolic remodeling in PD, with distinct sex-related metabolic signatures and a more pronounced and widespread metabolic dysregulation in males. Conclusions: These findings suggest that biological sex may contribute to systemic molecular heterogeneity in PD, with trends indicating more pronounced inflammatory and metabolic alterations in males and distinct immune-related responses in females. Given the exploratory nature of the study and the limited sample size, these observations should be interpreted cautiously and require validation in larger, independent cohorts. Nevertheless, the results support the importance of considering sex-related molecular differences in future biomarker studies and precision medicine approaches for PD. Full article

Atherosclerosis is a chronic multifactorial inflammatory vascular disease and the major risk factor for cardiovascular diseases (CVDs), characterized by arterial wall thickening, loss of arterial elasticity and the progressive accumulation of lipids and immune cells, ultimately leading to plaque formation and the development of unstable, rupture-prone plaques. Several studies suggest that gut microbiota might contribute to atherosclerosis, mainly by converting dietary and endogenous molecules into bioactive metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and the Gram-negative cell-wall component lipopolysaccharide (LPS). Such metabolites can promote key mechanisms involved in the development and progression of atherosclerotic plaque, and, importantly, plaque vulnerability. Specifically, they can worsen endothelial dysfunction, induce macrophage-driven inflammatory responses, and cause oxidative stress and extracellular matrix degradation. These processes are crucial for thinning of the fibrous cap and destabilization of atherosclerotic plaques. As a result, the risk of plaque rupture and related cardiovascular events increases. In this review, we summarize potential mechanisms by which the gut microbiota and their compounds induce the formation of vulnerable atherosclerotic plaques and discuss findings from experimental models and clinical studies that reveal the crucial role of microbiota–host dynamics in atherosclerosis. In contrast to previous reviews that primarily focused on atherosclerosis development, we specifically highlight the cellular and molecular mechanisms linking gut microbiota to plaque vulnerability and destabilization. We also address future research priorities to define microbiota-driven pathways better and develop targeted therapeutic interventions to reduce plaque vulnerability and cardiovascular risk. Full article

Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with central pain syndromes, weak correlation between structural disease severity and pain intensity, and symptom clustering during reproductive transitions such as puberty, pregnancy, and menopause. Methods: This study aims to synthesize clinical, molecular, neuroimmune, and endocrine evidence on the interrelationship between endometriosis and lipedema, and to propose a hypothesis-generating neuroimmune framework linking both conditions. This integrative narrative review conducted a non-systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science, focusing on mechanisms related to chronic pain, mast cell biology, TRPV1 signaling, CGRP-mediated neurogenic inflammation, intracrine steroidogenesis, and peripheral and central sensitization. Results: The review identifies convergent biological characteristics between the two diseases, including mast cell activation, macrophage polarization, endothelial dysfunction, fibrosis, angiogenesis, intracrine estrogen metabolism, and persistent inflammatory signaling. In endometriosis, direct evidence demonstrates increased sensory innervation, nerve growth factor expression, TRPV1 sensitization, CGRP-positive fibers, and mast cell-nerve interactions. In lipedema, convergent upstream mechanisms, including mast cell infiltration, elevated histamine levels, adipose tissue inflammation, and local estrogen activation, support the plausibility of a functionally analogous neuroimmune organization, despite incomplete direct neural characterization. In this context, the mast cell-TRPV1-CGRP axis is proposed as a biologically plausible framework, directly supported in endometriosis and currently hypothetical in lipedema, connecting peripheral sensitization, neurogenic inflammation, hormonal chronodependence, and central nociceptive amplification. The model further conceptualizes pain crises as transient events of instability within a sensitized neuroimmune network and proposes mechanistic phenotypes that integrate gastrointestinal, inflammatory, central, and hormonal triggers. Conclusion: Endometriosis and lipedema may represent topographically distinct manifestations of a shared neuroimmune process operating within hormone-sensitive tissues. Although the evidentiary basis remains asymmetric, with stronger mechanistic support in endometriosis than in lipedema, this framework provides a biologically plausible and experimentally testable model integrating endocrine, immune, neural, and vascular contributors to chronic pain amplification. This perspective supports coordinated translational investigation across reproductive biology, endocrinology, and pain medicine and may contribute to future mechanism-based stratification and therapeutic development. This work is hypothesis-generating and is not intended to establish causality or to provide clinical recommendations; all proposed mechanistic and therapeutic inferences require prospective experimental validation. Full article

Chronic atrophic gastritis (CAG) is a pivotal precancerous condition in gastric carcinogenesis, with progression typically following the classic Correa cascade. Although Helicobacter pylori (H. pylori) infection is widely recognized as the principal etiological factor, the persistence of gastric cancer (GC) risk in a subset of patients after successful eradication suggests that gastric microbiota dysbiosis may also contribute to CAG progression. In recent years, high-throughput sequencing technologies have revealed distinct microbial restructuring in patients with CAG, characterized by decreased microbial diversity, depletion of commensal taxa, and enrichment of opportunistic pathogens. These compositional changes are accompanied by metabolic dysfunction, activation of inflammatory signaling pathways, and disruption of immune homeostasis, which may contribute to a microenvironment permissive for precancerous transformation of the gastric mucosa. Probiotics and related microbiome-based therapeutics, including prebiotics, synbiotics, and postbiotics, have emerged as promising adjunctive strategies for H. pylori eradication and disease management. Their beneficial effects are mediated through multiple mechanisms, including remodeling of the microbial community, inhibition of pathogen colonization, modulation of host immune responses, and restoration of mucosal barrier integrity. However, whether these interventions can reverse established atrophic or metaplastic lesions remains unclear. In addition, how strain specificity, dose dependency, and interindividual heterogeneity influence clinical efficacy has yet to be fully elucidated. In this review, we summarize the compositional and functional features of gastric microbiota dysbiosis in patients with CAG, as well as the mechanisms and clinical applications of microbiome-based interventions. We further highlight current limitations in the field and discuss future directions for precision microecological therapies integrating multi-omics approaches, engineered probiotics, and artificial intelligence. These advances may provide a theoretical framework and practical guidance for the diagnosis and management of CAG and the prevention of GC. Full article

Bacillus subtilis has been widely investigated as a probiotic feed additive for weanling piglets due to its potential to improve growth performance, gut health, and disease resilience during the post-weaning period. This systematic review evaluated the effects of Bacillus subtilis supplementation in pigs following PRISMA guidelines and the PICOS framework. A total of 619 records published between 2000 and 2025 were identified through PubMed, Scopus, and AGRICOLA databases, of which 29 studies met the inclusion criteria for qualitative synthesis. Overall, Bacillus subtilis supplementation frequently improved average daily gain, body weight, feed efficiency, and reduced diarrhea incidence, particularly under enteric challenge conditions. Many studies also reported beneficial effects on intestinal morphology, immune regulation, intestinal barrier-related gene expression, nutrient digestibility, and modulation of gut microbiota toward bacterial communities associated with intestinal health. However, responses varied depending on Bacillus subtilis strain, dosage, diet composition, and experimental design. In contrast, effects on biochemical and oxidative stress indicators were less consistent across studies. Collectively, the findings support the potential role of Bacillus subtilis as a functional probiotic in swine nutrition while highlighting the need for standardized long-term studies to better define optimal strains, supplementation strategies, and mechanisms of action. Full article

Asthma is a heterogeneous chronic airway disease in which oxidative stress (OS) plays a central mechanistic role beyond classical immune-mediated inflammation. Reactive oxygen and nitrogen species (ROS/RNS), generated by recruited inflammatory cells and activated airway structural cells, drive epithelial injury, mucus hypersecretion, airway remodeling, and modulate key transcription factors including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. This review synthesizes current evidence on the multilevel redox-based determinants of asthma severity, spanning from genetic polymorphisms to circulating biomarkers. We examine serum antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxiredoxins (PRDXs), and the thioredoxin (Trx) system as dynamic indicators of systemic redox status and disease severity, alongside oxidative enzymes including NADPH oxidases and dual oxidases (NOX/DUOX), xanthine oxidase (XO), and myeloperoxidase (MPO) that serve as upstream sources of airway oxidant burden. Functional genetic polymorphisms in antioxidant genes (SOD2, CAT, glutathione S-transferase mu 1/glutathione S-transferase theta 1 (GSTM1/GSTT1), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/KEAP1)) and oxidative enzyme genes including nitric oxide synthase 1/2/3 (NOS1/2/3), MPO, cytochrome b-245 alpha chain (CYBA), and xanthine dehydrogenase (XDH) are reviewed as modulators of individual redox capacity and asthma susceptibility, with particular attention to gene–environment interactions. We further discuss oxidative damage biomarkers, including malondialdehyde (MDA), 8-isoprostanes, 4-hydroxynonenal, 8-oxo-7, 8-dihydro-2′-deoxyguanosine, protein carbonyls, 3-nitrotyrosine, and advanced oxidation protein products as indicators of lipid, DNA, and protein oxidation that correlate with disease activity and control. The roles of micronutrient cofactors in modulating antioxidant enzyme function and their potential as contextual biomarkers are also addressed. Additionally, emerging evidence on microRNAs (miRNAs) linked to OS biology in asthma is presented. Finally, we critically evaluate the challenges limiting clinical translation, including biomarker non-specificity, analytical variability, gene–environment complexity, and the absence of standardized reference ranges. This integrated framework supports the development of multilevel redox prognostic panels combining genetic, enzymatic, and oxidative damage readouts for improved asthma phenotyping, severity stratification, and personalized therapeutic approaches. Full article

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with an incompletely understood molecular pathogenesis. This systematic review aimed to synthesize current evidence on key molecular mechanisms underlying the disease, with a particular focus on immune dysregulation, epigenetic modifications, and tissue remodeling. A structured literature search identified studies employing transcriptomic, epigenetic, and experimental approaches. The strongest evidence consistently supports a central role of immune activation, particularly T cell-mediated responses involving Th1- and Th17-related pathways, accompanied by increased expression of pro-inflammatory cytokines and activation of the NF-κB signaling pathway. Epigenetic and post-transcriptional mechanisms, including dysregulated microRNAs (notably miR-155-5p) and altered DNA methylation patterns, may sustain immune imbalance and fibroblast activation partly via modulation of the FOXO signaling pathway. In parallel, experimental and multi-omics studies highlight enhanced fibroblast activity and extracellular matrix remodeling, largely associated with the TGF-β signaling pathway, linking inflammation with progressive fibrosis. Emerging data also suggest interactions between immune signaling and metabolic alterations, although these findings remain preliminary. Overall, the available evidence indicates that LS may involve a complex interplay between immune, epigenetic, and fibrotic mechanisms. While several molecular pathways and candidate biomarkers have been identified, their clinical relevance requires further validation in larger, well-designed studies. Full article