Search Results (1,257)

The aim of this review is to provide a narrative analysis of the role of Lactobacillus acidophilus as an active modulating factor in the prevention and treatment of cancer and allergic diseases. The paper discusses the molecular, metabolic, and bionanotechnological mechanisms of Lactobacillus acidophilus’s anticancer and immunomodulatory effects, which define this probiotic as an essential component of modern natural and functional medicine. A narrative review of the scientific literature was conducted, mainly from 2019–2026, focusing on the results of in vitro studies and studies on preclinical in vivo models, which analyzed the effect of live L. acidophilus strains, tyndallized bacteria (paraprobiotics) and cell-free supernatant from L. acidophilus cultures on, among others, immune system signaling pathways, tissue cytokine profile, and the integrity of the gastrointestinal epithelial cell barrier (enterocytes). Results indicate that L. acidophilus exerts significant antiallergic, antiproliferative, and proapoptotic effects against many types of cancer. Among other aspects, the ability of L. acidophilus to stimulate the production of anticancer exopolysaccharides and short-chain fatty acids, which directly influence the functioning of immune cells, is covered. The article thoroughly explains the immunomodulatory effects of L. acidophilus and the ability of this probiotic to regulate cytokine profiles, which helps promote an anti-inflammatory environment crucial for maintaining intestinal homeostasis. The article also discusses the direct interaction of L. acidophilus with immune cells, such as dendritic cells and macrophages, which leads to their activation and subsequent influence on the differentiation of T lymphocytes, which play a key role in the regulation of immune processes and in the development of immune tolerance. L. acidophilus is a universal mediator of immunological and metabolic homeostasis. Its ability to synergize with conventional therapies (chemotherapy, oncolytic virotherapy) and its innovative applications in the creation of postbiotics and paraprobiotics may provide a new approach to the treatment of inflammatory, allergic, and neoplastic diseases. Further clinical studies are necessary to assess the efficacy, safety, and optimal dose of this probiotic, which are essential for the widespread use of L. acidophilus in human therapy. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is characterized by diverse clinical presentations and complex immunological mechanisms. This study aimed to characterize patient serology associated with disease activity scored using the systemic lupus erythematosus disease activity index (SLEDAI) and investigate the molecular signature of complement activation (measured through C3dg, a complement breakdown product) in SLE patients utilizing high-throughput mass spectrometry and autoantibody profiling. Methods: Plasma samples from 39 SLE patients in four mutually exclusive groups based on either disease activity scores (high/low SLEDAI) or complement activation levels (high/low C3dg) were analyzed using rapid LC-MS/MS, followed by unsupervised and supervised protein expression analysis. Complement activation was evaluated by measuring C3dg levels, and disease activity was scored using SLEDAI. Autoantibody reactivities were profiled using global autoantibody protein microarrays. Data are available via ProteomeXchange with identifier PXD066214. Results: Differential proteomic analyses revealed 25 proteins associated with SLE disease activity (high vs. low SLEDAI scores) and 25 proteins linked to complement activation levels (high vs. low C3dg). Enriched pathways indicated that adaptive immune response, classical complement activation, and immunoglobulin production correlated with disease activity, while complement activation and coagulation cascades were primarily associated with complement activation levels. Autoantibody profiling highlighted distinct reactivity patterns between subgroups, suggesting varying degrees of immune-mediated tissue damage. Conclusions: In this study, disease activity and complement activation markers were associated with overlapping yet non-identical plasma proteomic patterns in SLE. These findings support the feasibility of rapid mass spectrometry-based proteomics and autoantibody profiling for generating candidate molecular signatures in SLE. These findings serve as exploratory signatures that require validation in larger independent cohorts before they can be considered for clinical stratification and decision-making. Full article

Visceral white spot disease caused by Pseudomonas plecoglossicida poses a severe threat to large yellow croaker (Larimichthys crocea) aquaculture. This study investigated the immunomodulatory effects and underlying mechanisms of Pseudostellaria heterophylla extract against P. plecoglossicida infection in L. crocea. Fish were fed a basal diet supplemented with 1% P. heterophylla extract for 30, 45, and 60 days, followed by intraperitoneal injection with 200 μL P. plecoglossicida (1 × 10⁴ CFU/mL). At 5 days post-infection, transcriptome sequencing of head kidney tissues was performed on the 45 and 60 days post-feeding of the treatment groups to analyze gene expression changes following bacterial infection. Survival rates of the treatment groups were 33.33%, 13.33%, and 20% higher than those of the control group at 30, 45, and 60 days post-feeding, respectively. Transcriptomic analysis revealed time-dependent transcriptional responses: in one group, 45 days post-feeding, 10 differentially expressed genes (DEGs) were identified (2 up-regulated and 8 down-regulated), whereas in another group, 60 days post-feeding, 893 DEGs were detected (417 up-regulated and 476 down-regulated). Functional enrichment analysis (GO, KEGG, and GSEA) demonstrated that DEGs were significantly enriched in immune-related pathways, including Toll-like receptor signaling, chemokine activity, Th1 and Th2 cell differentiation, hematopoietic cell lineage, and cytokine–cytokine receptor interaction. Key immune genes, including chemokines, Toll-like receptors, and T cell regulators, were significantly up-regulated. These findings indicate that P. heterophylla extract enhances both the specific and non-specific immune capabilities of L. crocea in a time-dependent manner, with prolonged supplementation eliciting more robust transcriptional activation of immune defense pathways. This study provides a scientific foundation for developing immunological prevention strategies against P. plecoglossicida infection in aquaculture. Full article

Rheumatoid arthritis (RA) is an autoimmune disease primarily characterized by chronic, erosive polyarthritis. It is associated with a high rate of disability, and its pathogenesis remains incompletely understood. Uncontrolled chronic inflammation, synovial hyperplasia, Pannus formation, and bone destruction in RA patients remain the core challenges facing current clinical treatment, and the inflammatory response is generally considered the initiating factor for this series of pathological processes. In an inflammatory environment, the body’s metabolic rate accelerates, leading to increased local oxygen consumption and ultimately creating a hypoxic microenvironment. Research has shown that under hypoxic conditions, glycolysis serves as the body’s primary energy pathway and is essential for sustaining the inflammatory response. Furthermore, lactate, a byproduct of glycolysis, functions not only as a metabolic byproduct but also as a precursor molecule; through lactylation, it contributes to the progression of RA. Although this metabolic–epigenetic axis is a common feature of various chronic inflammatory diseases, its effects on joint pathology may contribute to RA progression. Therefore, this article focuses on the intrinsic connections among hypoxia, glycolysis, and lactylation, and systematically reviews the immunological and inflammatory mechanisms of glycolysis in RA, the relationship between glycolysis and synovial hyperplasia, Pannus formation, and bone destruction in RA, and the role of lactate modification in promoting the pathological progression of RA. It also summarizes the latest research advances in RA therapies targeting hypoxia, glycolysis, and lactate modification, aiming to provide a theoretical basis for a deeper understanding of the pathogenesis of RA and the development of targeted treatment strategies. Full article

Atopic dermatitis (AD) is increasingly interpreted through frameworks emphasizing barrier dysfunction, type 2 cytokine signaling, pruritus pathways, and microbial dysbiosis, often relegating IgE-mediated mechanisms to secondary roles. In this narrative review, we synthesize historical, clinical, immunologic, and histopathologic evidence to propose a conceptual model in which IgE-bearing antigen-presenting cells (APCs)—including Langerhans cells, inflammatory dermal dendritic cells, and inflammatory dendritic epidermal cells (IDECs)—participate in an IgE-dependent amplification loop that may contribute to the chronicity of extrinsic (IgE-associated) AD. Evidence from human studies indicates that FcεRI-expressing APCs can acquire environmental allergens through IgE, enhancing antigen uptake and T-cell activation, while mast cells and basophils further reinforce type 2 inflammation through IgE-dependent and IgE-augmented pathways. Although these mechanisms have been described across distinct experimental and clinical contexts, their integration into a unified pathogenic circuit remains hypothesis-driven. We therefore present an interpretive framework that organizes these partially validated mechanisms into a coherent model linking cutaneous sensitization, allergen capture, APC activation, Th2 polarization, and spongiosis formation. This conceptual synthesis aims to reposition IgE-mediated processes within the broader pathophysiology of extrinsic AD and to highlight potential therapeutic implications for targeting IgE–FcεRI signaling and IgE-dependent APC biology. Full article

Immunotherapy has transformed cancer treatment; however, clinical benefit remains limited to a subset of patients, underscoring the need for robust biomarkers that capture tumor-immune interactions across cancer types. In this study, we performed a comprehensive pan-cancer, multi-omics characterization of the immune checkpoint–related molecules CD70, CD80, and TIGIT to evaluate their diagnostic, prognostic, and immunological relevance. Using integrative analyses of transcriptomic, epigenomic, genomic, pharmacogenomic, and single-cell RNA-sequencing data from The Cancer Genome Atlas and complementary resources, we assessed expression patterns, DNA methylation, somatic mutations, copy number alterations, immune infiltration, tumor stemness, and drug sensitivity. CD70, CD80, and TIGIT were broadly dysregulated across multiple malignancies, with coordinated overexpression particularly evident in kidney renal clear-cell carcinoma. Elevated expression of these immune checkpoints was associated with advanced tumor stage, aggressive molecular subtypes, and unfavorable survival outcomes in selected cancers, including uveal melanoma and renal malignancies. Functional analyses revealed significant associations between checkpoint expression and key oncogenic pathways, including epithelial–mesenchymal transition, apoptosis, and hormone receptor signaling, suggesting links with tumor progression and immune activation states. Immune deconvolution analyses indicated that TIGIT expression is associated with a T-cell–inflamed microenvironment and reduced neutrophil infiltration, while CD80 exhibited methylation-dependent associations with immune cell composition. Genomic and epigenetic alterations were found to correlate with checkpoint expression patterns and immune phenotypes across tumor types. Pharmacogenomic profiling identified associations between checkpoint expression and sensitivity to multiple anticancer agents; however, these findings are based on cell line datasets and should be considered predictive. Single-cell transcriptomic analyses further resolved cell-type–specific expression patterns, distinguishing tumor-intrinsic from immune-restricted expression profiles. Collectively, our findings establish CD70, CD80, and TIGIT as integrative biomarkers of tumor progression, immune contexture, and therapeutic response, providing a rationale for their clinical exploitation in precision immuno-oncology. Full article

During pregnancy, hormonal, metabolic, and immunological changes influence the composition and function of maternal microbial communities. Increasing evidence suggests that the maternal microbiota—particularly in the vaginal, gut, and oral environments—plays a significant role in maintaining pregnancy homeostasis and supporting fetal development. In healthy pregnancies, the vaginal microbiota is typically dominated by Lactobacillus species, which help maintain a low vaginal pH and protect against ascending infections. However, disruption of this balance (vaginal dysbiosis) has been associated with obstetrical complications such as intrauterine infection and preterm birth. Similarly, the maternal gut microbiota undergoes trimester-specific changes that contribute to metabolic adaptations required for fetal growth, while alterations in microbial composition have been linked to metabolic disorders including gestational diabetes mellitus and preeclampsia. Changes in oral microbiota and periodontal disease have also been associated with adverse pregnancy outcomes through systemic inflammatory pathways and potential microbial translocation to the placenta. Recent advances in sequencing technologies have improved the understanding of host–microbiome interactions in pregnancy, although the existence of a placental microbiome remains controversial. Overall, maternal microbiota plays an important role in pregnancy physiology, and its dysregulation may contribute to obstetrical complications. Understanding these mechanisms may facilitate the development of microbiome-based diagnostic and therapeutic strategies in maternal–fetal medicine. Full article

Extracellular vesicles (EVs) are key mediators of intercellular communication across biological kingdoms, with central roles in immune regulation and disease processes. Despite shared structural features, EVs derived from bacteria, plants, and mammalian cells differ substantially in their biogenesis, molecular composition, and immunological functions. EV formation pathways generate vesicles with distinct cargo profiles, including pathogen-associated molecular patterns (PAMPs) in bacterial EVs, regulatory small RNAs in plant-derived vesicles, and cytokines, microRNAs, and antigen-presenting complexes in mammalian EVs. Differences in cargo result in divergent immune outcomes. Bacterial EVs predominantly activate innate immunity via pattern recognition receptors such as Toll-like receptors, whereas plant-derived EVs exhibit low immunogenicity and mediate cross-kingdom RNA interference. In contrast, mammalian EVs primarily regulate immune responses by modulating antigen presentation and cytokine signaling. These findings support a framework in which EV origin determines immunological function and therapeutic applicability. This perspective highlights the importance of selecting appropriate EV sources for vaccine development, regenerative medicine, and targeted delivery strategies, while addressing current challenges related to heterogeneity, standardization, and safety. Full article

Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acquired resistance—including immune exclusion, myeloid-dominant suppression, and genotype-driven “cold” tumor states. In this review, we synthesize emerging insights into the immune landscape of CCA, integrating data from single-cell, spatial, and translational studies to define the cellular and molecular circuits governing immune evasion. Beyond canonical biomarkers such as mismatch repair and microsatellite status, we highlight how spatial organization of immunity—in particular, tertiary lymphoid structures, dynamic myeloid and stromal interactions, and pathway-level features—shape immunotherapy responsiveness. We also examine how tumor-intrinsic alterations, including IDH1 mutation, FGFR2 fusions, KRAS activation, and MTAP loss, define distinct immunologic phenotypes with direct implications for immunotherapeutic response and biomarker-driven patient selection. We evaluate the expanding clinical trial landscape of immunotherapy in CCA and more broadly in BTC, including adoptive cell therapies and cancer vaccines. Together, these advances position CCA as a paradigm of how tumor genotype and microenvironment co-evolve to define immunotherapy sensitivity and resistance. Full article

Propolis is a natural resinous product with a broad spectrum of biological activities, including immunomodulatory and anti-inflammatory effects. Increasing evidence suggests that propolis may influence pathways involved in tissue remodeling and fibrosis; however, comparative studies evaluating different propolis types in endothelial models remain limited. Brain microvascular endothelial cells, as a key component of the blood–brain barrier, constitute a relevant in vitro model for studying anti-inflammatory and neurovascular responses under both physiological and pathological conditions. The aim of this study was to compare the effects of Brazilian green propolis (EEP-BRA) and Polish brown propolis extracts (EEP-PL) on the immunological and fibrotic responses of brain microvascular endothelial cells. Human brain microvascular endothelial cells (hCMEC/D3-BBB) were exposed to propolis extracts (EEP-BRA and EEP-PL) under normoxic and hypoxic conditions to reflect diverse microenvironmental states. The analysis focused on the modulation of release of selected cytokines, including IL-10, IL-4, IL-6, IFN-γ, GM-CSF, TNF-α, IL-2, IL-8, and TGF-β, with particular emphasis on TGF-β as a key regulator of fibrosis. Results: Both propolis extracts significantly modulated cytokine production, although their effects differed depending on the origin of the propolis and oxygen conditions. Under the hypoxia condition followed by IFN-α stimulation, EEP-PL-50 was associated with reduced TNF-α (0.54 vs. 3.61 pg/mL; Hedges g = −6.78; large effect size, p > 0.05) and decreased TGF-β1, IL-8 and TGF-β2/β3. EEP-BRA-50 elicited a distinct profile characterized by increased IL-6 (171.58 vs. 27.63 pg/mL; p < 0.001; g = +6.15) and GM-CSF, while reducing TGF-β1. Both extracts preserved viability > 70% (ISO 10993-5). In conclusion, the results demonstrate that EEP-BRA and EEP-PL exert distinct immunomodulatory effects on brain endothelial cells. These findings highlight the importance of propolis origin in determining its biological activity and support its potential application in modulating inflammation and neurovascular responses. Full article

Immune-mediated myocardial injury is an important yet underrecognized manifestation of systemic rheumatic diseases and represents a biologically heterogeneous process extending beyond traditional cardiovascular complications such as pericardial disease or accelerated atherosclerosis. This review aimed to summarize current evidence regarding the molecular mechanisms underlying autoimmune myocardial injury and propose an integrated pathogenic framework. A structured narrative review of the literature was performed, focusing on molecular and cellular mechanisms, disease-specific pathogenic pathways, advances in cardio-immunology, and contemporary diagnostic approaches in autoimmune myocardial disease. Current evidence indicates that myocardial injury in rheumatic diseases results from complex interactions involving autoantibody-mediated injury, immune complex deposition, endothelial dysfunction, coronary microvascular dysfunction, dysregulated innate and adaptive immunity, oxidative stress, mitochondrial dysfunction, immunometabolic reprogramming, and regulated cardiomyocyte death. These mechanisms contribute to heterogeneous clinical manifestations, including myocarditis, arrhythmias, inflammatory cardiomyopathy, and heart failure. An integrated immune–microvascular–immunometabolic framework may represent a central mechanism driving myocardial injury and progression to inflammatory cardiomyopathy, supporting earlier diagnosis, improved risk stratification, and the development of precision therapeutic strategies. Full article

Diabetes mellitus (DM) fundamentally disrupts the oral microbiome, initiating a dysbiotic shift that drives progressive periodontal tissue breakdown. This transition is mediated by complex, bidirectional immune crosstalk, primarily centering on the upregulation of the Th17/Interleukin-17 (IL-17) inflammatory pathway. This systematic review and meta-analysis quantified the specific impact of this diabetic microbiota on immune activation and periodontal destruction. A comprehensive search of PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library was conducted for studies published up to 2026. Eligible studies included assessing oral/salivary microbiome shifts and their localized or systemic immunological consequences in diabetic periodontitis. A random-effects meta-analysis synthesized standardized mean differences (Hedges’ g) to evaluate the magnitude of these effects. Quantitative synthesis of preclinical data (four studies yielding eight discrete comparisons) revealed that exposure to a diabetic/dysbiotic microbiota significantly increased overall immune activation and periodontal inflammation relative to eubiotic controls (pooled Hedges’ g = 3.73, 95% CI 2.96–4.51). Subgroup analyses confirmed profound, statistically significant effects specifically on the Th17/IL-17 axis (g = 4.03) and periodontal bone destruction pathways (g = 3.37). Preclinical murine data suggests diabetes-associated oral dysbiosis may contribute to periodontal destruction by upregulating the Th17/IL-17 immune axis. However, direct extrapolation to humans is restricted, necessitating further clinical studies to validate these findings. Full article

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by demyelination, neuroinflammation, and progressive neurodegeneration. While there is a small component of genetic susceptibility to MS risk, environmental factors, including infectious exposures, are gaining increased recognition as playing a critical role in MS initiation and progression. Viral infections, especially by Epstein–Barr virus (EBV), have emerged as strong candidates and triggers of MS symptoms, through antibody-mediated molecular mimicry and B-cell dysregulation. In contrast, parasitic infections, including helminths and select protozoa, appear to exert neuroprotective effects by skewing immune responses toward regulation and tolerance. In this review, we examine antibody-driven mechanisms by which viral pathogens promote autoimmunity in MS and contrast these with parasite-induced immunoregulatory pathways that suppress pathogenic inflammation. We further discuss diagnostic and therapeutic implications, highlighting how insights from infectious immunology may inform novel strategies for MS treatment. Full article

Postoperative inflammation is a necessary response to surgical injury that supports tissue repair and regeneration. However, successful healing depends not only on the initial inflammatory response but also on its timely resolution. Failure to resolve inflammation can impair wound healing, promote fibrosis, and increase the risk of postoperative complications. Increasing evidence suggests that effective recovery is driven by the transition from inflammation to repair and regenerative processes. Diet plays an important role in this transition, as nutrients not only provide metabolic support but also regulate key pathways involved in inflammation, tissue regeneration, redox balance, and immune function. Omega-3 polyunsaturated fatty acids could serve as precursors for specialized pro-resolving mediators that actively terminate inflammation and may promote macrophage-driven tissue repair. Polyphenols and antioxidant micronutrients modulate NF-κB and Nrf2-dependent signalling, attenuating oxidative amplification of inflammatory cascades. Micronutrients and amino acids further regulate enzymatic processes governing collagen synthesis, angiogenesis, and immune competence. Concurrently, diet-driven preservation of gut barrier integrity limits endotoxin-mediated amplification of systemic inflammatory responses. By targeting interconnected molecular networks, including inflammasome activation, mitochondrial redox signalling, and metabolic programming of immune cells, anti-inflammatory dietary patterns may promote immune resolution rather than immunosuppression. This distinction is particularly relevant in the postoperative setting, where balanced inflammation is required for both host defence and regenerative healing. This review synthesizes current molecular and translational evidence linking dietary modulation to postoperative inflammatory control and tissue regeneration. By integrating insights from immunology, metabolism, and nutritional science, it positions diet as an active, biologically grounded component of perioperative management and highlights future directions for precision nutrition strategies aimed at optimizing surgical recovery. Full article

Background: Prolonged intermittent fasting is associated with metabolic and immune adaptation; however, the extent to which transcriptional immune responses translate into systemic inflammatory changes, and how these processes relate to autophagy, senescence-associated signaling, and inflammasome regulation, remains incompletely understood. Methods: This study represents a secondary integrative analysis of a previously characterized cohort of healthy young men undergoing Ramadan fasting. Longitudinal data across four time points (T1–T4) were re-analyzed, integrating targeted mRNA profiling of autophagy-, senescence-, and inflammasome-related genes with circulating cytokines and clinical parameters. Baseline-stratified regression and exploratory clustering were applied to assess inter-individual variability. Results: Fasting was associated with modest reductions in body weight (−1.78 ± 1.44 kg, FDR < 0.001) and BMI (−0.56 ± 0.47 kg/m², FDR < 0.001), without hemodynamic instability. Autophagy-related transcripts (ULK1, ATG5) were upregulated, while senescence markers showed divergent regulation (p53↑, p21↓). Inflammasome-related genes (NLRP3, IL1B) increased at the transcriptional level; however, circulating IL-1β and IL-6 remained stable and TNFα decreased (FDR < 0.001), indicating dissociation between transcriptional priming and systemic cytokine output. ΔNLRP3 was inversely associated with baseline expression (β = −1.88, R² = 0.31, p = 0.0056), suggesting baseline-dependent transcriptional responsiveness. Responses followed a continuous spectrum rather than discrete subtypes. Conclusions: Prolonged intermittent fasting is associated with coordinated immunometabolic remodeling characterized by transcriptional changes in autophagy-, senescence-, and inflammasome-related pathways, without systemic inflammatory escalation. Inflammasome-related responses appear baseline-dependent, suggesting graded immunological responsiveness rather than a uniform activation. These findings are hypothesis-generating and support the interpretation of fasting as a graded immunometabolic modulator rather than a uniform pro-inflammatory stimulus within the limitations of a secondary exploratory analysis. Full article