Search Results (5,347)

Immunosenescence is a critical driver of tumor initiation and progression. In this study, we systematically characterized immune cell senescence by integrating transcriptomic profiles from 17 physiologically aged tissues with pan-cancer single-cell datasets, encompassing 206 samples across nine cancer types. Cross-tissue comparison of senescence-associated alterations, integrated with spatial transcriptomics, revealed that malignant cells triggered senescence in the core myeloid subpopulation designated Mac_DAB2 via a conserved MIF-CD74 signaling axis. By integrating shared myeloid differentiation programs across normal tissues and the tumor microenvironment (TME) with their transcriptional regulatory networks, we defined a myeloid senescence-associated gene (MSAG) signature. This signature successfully distinguishes a senescence-associated, immunosuppressive subtype linked to poor prognosis in pan-cancer cohorts. Finally, we established the MSAG.SIG prognostic model using an ensemble framework of 117 machine learning algorithms, which demonstrated robust and consistent predictive performance across multiple independent cohorts. Overall, this study elucidates the mechanisms underlying TME-driven myeloid senescence, establishes MSAG as a conceptual framework for characterizing myeloid immunosenescence, and provides a clinically relevant pan-cancer prognostic tool with translational potential. Full article

Vibrio tubiashii infection has led to several Babylonia areolata pandemics on the southeast coast of China, yet the immune response of the ivory shell against V. tubiashii and the specific pathogen–host interaction remain unclear. This dynamic study aimed to characterize the response of B. areolata to V. tubiashii infection with the use of pathology, transcriptomics, an enzymatic assay, and inflammatory cytokines. Hepatopancreatic cells showed marked vacuolar degeneration with intact cell membrane and extensive cytoplasmic vacuolization after infection. The dynamic transcriptome of the hepatopancreatic tissue was analyzed by RNA-seq after V. tubiashii infection, and a total of 2733 (3 h), 5610 (24 h), 3323 (48 h), and 418 (72 h) differentially expressed genes (DEGs) were identified during infection. The GO and KEGG analyses showed that the DEGs were enriched in metabolic regulation, lysosome, and multiple immune-related pathways such as the MAPK signaling pathway. The immune response of B. areolata was distinct, where the early stage of immune response (3 h) showed binding, focal adhesion, and apoptosis, as well as an activated antioxidant system. Here, expression of TNF-α, IL-1, and IL-8 was significantly increased in the hepatopancreas, whereas expression of IL-6 and IL-17 increased afterward. During the middle stage (24 h and 48 h), a large number of DEGs were suppressed, especially those associated with metabolism and lysosomes, although their expression returned to normal during prolonged infection (72 h). The PPI network showed that ppp2, atp6, and sos1 were the top immune-related DEGs during infection. Key infection-related and time-course-related genes were analyzed by WGCNA. This study illustrates that oxidative stress, inflammation, and apoptosis are strategies of the hepatopancreatic immune response in B. areolata against V. tubiashii infection and enlightens conservation and production by furthering our understanding of gastropod immunity. Full article

Mucosal immunity in the respiratory tract provides the first line of defense against airborne pathogens, yet most current vaccines fail to induce strong and durable immune responses at these sites. Respiratory viruses, including respiratory syncytial virus (RSV), influenza viruses, and coronaviruses, remain major global health threats, in part due to their ability to evade long-term mucosal protection. Although systemic vaccination generates robust circulating immunity, it induces limited local responses, particularly secretory immunoglobulin A (IgA), which is critical for preventing viral entry and transmission at the airway surface. The mechanisms regulating B cell responses within the airway mucosa are not fully understood. B cell–activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, has emerged as an important context-dependent regulator of mucosal B cell immunity. BAFF is produced by airway epithelial cells and multiple myeloid populations, including dendritic cells and neutrophils, and is rapidly induced during respiratory viral infection through type I interferon–dependent pathways. Functionally, BAFF supports B cell survival, differentiation, and class-switch recombination, promoting the generation of antibody-secreting plasma cells and enhancing IgA production. In the lung, these effects align with early, intermediate, and late stages of the response, supporting initial local antibody production, the formation of inducible bronchus-associated lymphoid tissue (iBALT), and the development of tissue-resident memory B cells that sustain long-term immunity. Although BAFF plays an essential role in mucosal immunity, its activity requires tight regulation to maintain immune balance. Current evidence supports BAFF as a promising immunomodulatory component and highlights its potential as an adjuvant platform for enhancing mucosal vaccine efficacy, warranting further investigation as a potential adjuvant in this context. Full article

Immune remodeling within the tumor microenvironment (TME) influences the progression and clinical outcome of uterine corpus endometrial carcinoma (UCEC), but the contribution of chemokine-related regulatory genes remains incompletely characterized. This study aimed to evaluate the prognostic relevance of CXCL13 and its association with immune microenvironmental features in UCEC using publicly available transcriptomic and single-cell datasets. RNA-sequencing profiles and clinical annotations from 589 UCEC cases in The Cancer Genome Atlas (TCGA) were analyzed to assess TME composition using ESTIMATE (Estimation of Stromal and Immune cells in MAlignant Tumours using Expression data) and CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts), followed by survival analysis, differential gene expression analysis, protein–protein interaction network construction, Cox regression, and gene set enrichment analysis. A public single-cell RNA-sequencing dataset from the Gene Expression Omnibus (GEO; GSE173682) was further used to infer the cellular sources of CXCL13. Elevated CXCL13 expression was associated with favorable overall survival and enrichment of immune-activation pathways. CIBERSORT-based analysis indicated that high CXCL13 expression correlated with increased estimated fractions of CD8⁺ T cells and plasma cells, together with transcriptional features related to tertiary lymphoid structure-associated immune activation, whereas several immunosuppressive cell populations showed lower estimated abundance. Single-cell analysis suggested that CXCL13 was mainly expressed by follicular helper T cells and exhausted CD8⁺ T cells. These findings indicate that CXCL13 may serve as a prognostic biomarker associated with an immune-active TME in UCEC. Further histological, spatial, and functional validation is warranted to confirm its mechanistic role and translational potential. Full article

Brucellosis and tuberculosis (TB) are chronic infectious diseases of international public health importance, with developing countries being most affected. The diagnosis of brucellosis and tuberculosis co-infection remains challenging because both diseases present with overlapping nonspecific clinical manifestations, such as prolonged fever, fatigue, and weight loss, and elicit similar cell-mediated immune and inflammatory responses, which can complicate differential diagnosis, particularly in endemic regions. Recently, it has been shown that chronic infections affect cell stress pathways such as oxidative stress and telomere function. The current literature review provides an overview of the relationship between brucellosis and TB at a molecular level, focusing on telomere biology, oxidative stress and the mechanisms of antimicrobial resistance. Due to chronic immune response in brucellosis and TB patients, an increase in reactive oxygen species (ROS) levels is observed, leading to DNA damage and subsequent telomere shortening and alteration of telomerase activity. These alterations might be responsible for immune senescence, weakened defense response and persistent infection. In addition, different methods of drug resistance have been discovered among brucellae and mycobacteria, such as mutation in target sites, efflux systems and intracellular persistence, making their eradication difficult. Finally, the potential role of telomere-related genes and biomarkers of oxidative stress in diagnosis and prognosis is also highlighted. Insights into these interrelated pathways would allow us to have a better understanding of host–pathogen interactions and hence offer a possible means of developing new strategies in the fight against co-infection by finding new biomarkers. Full article

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

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article

Neuroinflammation is a key hallmark of both neurodegenerative and neurospecific autoimmune diseases, including multiple sclerosis (MS), where immune dysregulation contributes to cellular stress, autophagy, and disease progression in Alzheimer’s disease (AD), Parkinson’s disease (PD), and MS. Emerging evidence suggests a shared mechanism behind MS, AD, and PD, driven by chronic interaction between the peripheral immune system and the central nervous system (CNS). While MS was traditionally viewed as a primary autoimmune condition, recent research indicated that all three disorders involve a breakdown of the blood–brain barrier (BBB). This structural failure enables peripheral immune cells and cytokines to enter the brain, causing sustained neuroinflammation and accelerating disease progression. Here, we propose an end-to-end framework for identification of the diagnostic and therapeutic cell-specific protein markers commonly regulated in mild–moderate AD (MMAD), early-stage PD (ESPD), and MS within peripheral blood mononuclear cells (PBMCs). PBMC markers were first identified based on shared differential protein expression, followed by filtering for BBB permeability. Subsequently, sorted cell markers were mapped to disease-specific neural cell types. Our analysis suggests that PBMC-derived cells, including astrocyte- and monocyte-like populations, share overlapping transcriptional signatures and functional similarity with macrophages and neuroglial cells, indicating potential transcriptional similarity or functional convergence. Furthermore, intra- and inter-cellular pathway analysis suggested both shared and disease-specific signaling mechanisms, with kinase–integrin interactions emerging as key regulatory factors. Selected potential seed markers, primarily kinases and immunoglobulins, were further analyzed through evolutionary sequence–structure space to identify druggable structural features. Next, protein moonlighting possibilities were tested to enhance the temporal functional trajectory of the markers for precise therapeutic impact. Hence, the framework provides a robust strategy to identify immune-based disease-specificcandidate diagnostic andpotential therapeutic targets. 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). When the control group reached about 50% mortality, 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

Chronic kidney disease (CKD) is common in older cats, but cortical transcript-level relationships among hypoxia response, iron handling, and lipid oxygenation are poorly defined. This analysis-plan-guided, hypothesis-generating secondary analysis used public feline renal RNA-seq data (GSE303653). The internal plan fixed the gene panel, composite construction, primary inferential test, and quality-control thresholds before the review of the present expression results, but was not publicly registered. After technical quality control, 21 renal cortex samples from control, CKD 1/2, and CKD 3/4 cats were analyzed. A 23-gene panel and whole-transcriptome differential expression were evaluated using likelihood ratio testing as the primary panel-level screen, with pairwise DESeq2 contrasts, Spearman summaries, enrichment, medulla, composite, and marker-set analyses as secondary or exploratory context. VEGFA, FTL, and NCOA4 decreased with ordinal disease group, whereas ALOX5 and HIF1A increased; eight panel genes were stage-associated by likelihood ratio testing. The equal-weight composite was nonmonotonic. Advanced CKD enrichment was dominated by immune and inflammatory terms, while GPX4 and ferroptosis-pathway enrichment were not stage-significant. The findings support heterogeneous transcript-level remodeling, including ALOX5-associated inflammatory/lipid-oxygenation signal and HIF1A–VEGFA divergence, rather than evidence of ferroptotic cell death, pathway activation, or cell-specific mechanism. Full article

Interleukin-13 receptor α2 (IL-13Rα2) has traditionally been considered a decoy receptor; however, its cellular functions beyond the immune system remain unclear. We aimed to investigate the role of IL-13Rα2 in C2C12 myoblast proliferation and differentiation. IL-13Rα2 expression was knocked down in C2C12 cells using siRNA. Myogenic differentiation was evaluated by myosin heavy chain (MyHC) immunostaining and by quantifying the expression of myogenic regulatory and fusion-related genes. Myoblast proliferation was assessed using BrdU incorporation and cell number analyses, and signaling events induced by IL-13Rα2 knockdown were analyzed via immunoblotting and immunocytochemical analysis. IL-13Rα2 knockdown did not alter myogenic differentiation or the expression of fusion-associated genes. In contrast, IL-13Rα2 knockdown significantly increased BrdU incorporation and cell number, accompanied by increased Akt phosphorylation and decreased ERK phosphorylation. Cyclin D1 and cyclin-dependent kinase 4 (CDK4) levels were also increased. Akt inhibition abolished the enhanced proliferation and normalized Cyclin D1/CDK4 levels, whereas ERK activation did not further modify the knockdown-associated phenotype. These findings demonstrate that IL-13Rα2 negatively regulates myoblast proliferation by modulating the Akt–Cyclin D1–CDK4 signaling pathway, while being dispensable for myogenic differentiation. Full article

Dengue virus (DENV) and chikungunya virus (CHIKV) co-circulate in many regions and present with overlapping clinical features, which complicate accurate diagnosis and disease management. This study develops an integrative transcriptomic framework to identify robust host gene signatures that distinguish between dengue, chikungunya, and healthy states. Publicly available RNA sequencing (RNA-seq) datasets derived from human blood samples were analyzed using a cross-validation design to ensure robustness and prevent information leakage. Differential expression analysis was performed independently within each dataset using the Generalized Linear Models with Quasi-Likelihood F-tests and Magnitude–Altitude Scoring (GLMQL-MAS) framework, followed by Cross-Magnitude–Altitude Scoring (Cross-MAS) integration to identify shared and virus-specific gene signatures. A strict consensus approach across folds was applied to derive reproducible gene sets. These signatures were used for dimensionality reduction and multinomial logistic regression to evaluate classification performance. A small subset of selected genes showed strong discriminative performance within the cross-validation framework, with test balanced accuracy reaching 0.97, which improved upon models using all genes. Biologically, both infections exhibited a shared antiviral response characterized by interferon signaling and innate immune activation. However, distinct virus-specific patterns were identified. Dengue infection was associated with cell-cycle and DNA replication pathways, while chikungunya infection showed stronger enrichment of inflammatory and immune signaling pathways, including NF-kappaB and Toll-like receptor signaling. Overall, this study provides a cross-validation-based framework for integrative transcriptomic analysis and identifies compact, reproducible host-response signatures with strong discriminative signals in the analyzed cohorts. These signatures require validation in larger independent cohorts before any clinical or diagnostic application. Full article

Vitamin D is a fat-soluble secosteroid essential for skeletal development and calcium homeostasis, but it also exerts pleiotropic effects on numerous biological processes via its active metabolites. Vitamin D metabolites act as steroid hormones that regulate cell-cycle progression, proliferation, differentiation, apoptosis, immune responses, and multiple intracellular signaling pathways. Moreover, they modulate the expression of genes involved in carcinogenesis. As circulating vitamin D levels are influenced by diet, fortified foods, and supplementation, they represent a potentially modifiable factor. Whether vitamin D status affects cancer risk or disease progression in carriers of pathogenic BRCA1 variants remains unclear and continues to be actively investigated. Clarifying this relationship could have significant clinical implications for risk stratification and prevention in this high-risk population. This narrative review summarizes current evidence from epidemiological, clinical, and molecular studies examining the role of vitamin D in BRCA1 pathogenic variant carriers. It also highlights key limitations in the existing literature and identifies critical directions for future research, emphasizing the need for well-designed prospective studies in representative cohorts. Full article

Gastrointestinal symptoms (GI) (abdominal pain, vomiting, and diarrhea) during the febrile phase of dengue (less than 5 days from fever onset) might indicate prominent innate immune responses. Serum and feces samples from cases with GI symptoms versus those without GI symptoms (n = 20 per group) were analyzed. From these, only the neutrophil extracellular traps (NETs), serum fibroblast growth factor (FGF) 21, and fecal microbiome analyses, but not the routine parameters, endotoxemia, or serum cytokines, were higher in the GI cases than in the non-GI cases. From the in vitro experiments, both lipopolysaccharide (LPS) and the dengue virus (DENV) upregulated the FGF receptor 1 (FGFR1) and cytokines in hepatocytes (HepG2) and THP-1-differentiated macrophages. Meanwhile, LPS and DENV induced NETs in isolated neutrophils from healthy volunteers. Only the starvation protocol, but not LPS or DENV, enhanced supernatant FGF-21 from hepatocytes. Incubation of recombinant FGF-21 in LPS + DENV-activated cells (hepatocytes, macrophages, and neutrophils) attenuated inflammation, as determined by supernatant cytokines and NETs. Hence, abdominal symptoms in dengue during the febrile phase indicate prominent innate immune responses, as detected by NETs and FGF-21 (an acute-phase protein), implying significant hepatic stress with a possible counteracting anti-inflammation. Full article

Invertebrates rely exclusively on innate immunity but exhibit memory-like responses termed immune priming or trained immunity. In the commercially vital whiteleg shrimp (Litopenaeus vannamei), infection by Vibrio parahaemolyticus causes severe economic losses, yet the molecular networks driving secondary immune recall remain poorly understood. In this study, we established a two-step immune challenge model in L. vannamei using formaldehyde-inactivated V. parahaemolyticus and performed transcriptomic analysis on hemocytes to compare primary and secondary immune responses. Differentially expressed gene (DEG) screening and enrichment analyses (GO, KEGG, and GSEA) suggest that shrimp hemocytes undergo a broad and coordinated transcriptional reprogramming rather than uniform upregulation of immune genes. Transcriptomic data show potential associations between secondary immune priming and the modulation of cell fate processes: genes related to cell cycle progression (e.g., CDK1, CCNB3) and spindle assembly (e.g., MPS1) were significantly upregulated alongside apoptosis inhibition (CASP6 downregulation). Concurrently, metabolic remodeling was observed through the upregulation of lipid synthesis (SREBF1, FASN) and carbohydrate uptake pathways, potentially providing anabolic support for hemocyte growth and immune activation. Furthermore, the humoral effector responses appear to be strengthened, characterized by upregulated antimicrobial peptides (PEN, ALF) and the proPO melanization cascade (PPAF3, PPO3), whereas the expression of intracellular NLR was relatively suppressed, which might help mitigate excessive immune inflammation and immunopathological damage. Collectively, these transcriptomic findings identify a putative coordinated transcriptional signature of hemocyte recall responses in L. vannamei. This study expands our understanding of innate immune memory in invertebrates and provides candidate molecular markers for further study in disease-resistant breeding research in shrimp aquaculture. Full article