Search Results (1,170)

Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. Full article

Background/Objectives: Solid tumors are characterized by a dense stromal structure and heterogeneous microenvironments that limit intratumoral drug penetration and contribute to immune exclusion. We developed perfluoropentane (PFP)-based phase-change nanodroplets (IMP700) and aimed to identify focused ultrasound (FUS) parameters that enhance cavitation and sonoporation to improve drug delivery and immune engagement in tumor models. Methods: IMP700 was prepared as lipid-shelled PFP nanodroplets and physicochemically characterized. Acoustic droplet vaporization (ADV), echogenicity, and cavitation were evaluated in vitro and in vivo using ultrasound imaging and cavitation analysis under varying FUS parameters, including acoustic intensity, duty cycle, and pulse repetition frequency (PRF), in PANC-1 xenograft tumors. Sonoporation was assessed by co-administering an ultrasound-responsive doxorubicin liposome (IMP301), and intratumoral drug distribution was analyzed by confocal imaging. Immune responses were evaluated in a syngeneic 4T1 tumor model by quantifying CD8⁺ T-cell infiltration after repeated treatments. Results: IMP700 exhibited nanoscale size and high PFP encapsulation efficiency and underwent ADV with increased echogenicity and intensity-dependent cavitation. In vivo, a 2% duty cycle and 10 Hz PRF produced strong and reproducible cavitation. Under these conditions, IMP700 markedly increased inertial cavitation and enhanced intratumoral drug penetration compared to FUS alone. Combined IMP700 and FUS treatment also increased intratumoral CD8⁺ T-cell infiltration. Conclusions: IMP700 amplifies FUS-induced cavitation, improves sonoporation-mediated drug delivery, and promotes CD8⁺ T-cell infiltration, which supports the use of FUS-activated nanodroplets as a strategy to overcome stromal and immunological barriers in solid tumors. Full article

Cyanobacteria of the genus Phormidesmis are recognized as a promising source of biologically active secondary metabolites with anticancer and immunomodulatory properties. In the present study, we investigated both the cytotoxic and immunological effects of an extract obtained from Phormidesmis molle PACC (Plovdiv Algal Culture Collection) 8140 as well as its chemical composition. The extract was profiled by LC-ESI-MS/MS (Liquid chromatography—electrospray ionization—tandem mass spectrometry), and selected compounds were evaluated with in silico ADMET (Absorption, distribution, metabolism, excretion and toxicity) modeling. The cytotoxic potential of the extract was evaluated in vitro using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay on human colorectal adenocarcinoma cell lines (Caco-2, HT-29, and LS-180). The immunological impact of the extract was assessed on human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. PBMCs were treated with 100 µg/mL extract for 48 h, followed by flow cytometric immunophenotyping and ELISA (Enzyme-linked immunosorbent assay)-based cytokine quantification. The extract induced a concentration- and time-dependent decrease in cancer cell viability after 24, 48, and 72 h of exposure. At 72 h, treatment with the highest concentration (200 µg/mL) reduced cell viability to 74% in Caco-2 cells, 69–70% in HT-29 cells, and 59–61% in LS-180 cells. Morphological changes observed after treatment with Phormidesmis extract showed pronounced cytotoxic and apoptosis-related effects in the colorectal cancer cell lines tested. Immunophenotyping revealed a pronounced expansion of natural killer (NK) cells (CD56⁺ and/or CD16⁺). CD3⁻CD56⁻CD16⁺ NK population was markedly increased (from 67.7 ± 0.95% in non-treated PBMCs to 94.66 ± 0.90% in extract-treated PBMCs, p < 0.001). In contrast, the proportions of CD8⁺ T cells, CD19⁺ B cells, and CD11b⁺ monocytes were significantly reduced (from 21.5 ± 4.50% to 7.22 ± 0.41%, from 11.9 ± 1.70% to 6.06 ± 0.42%, and from 66.4 ± 0.60% to 34.4 ± 0.87%, respectively). Cytokine analysis demonstrated strong suppression of Th1-associated cytokines, with significantly reduced interferon gamma (IFN-γ, 461 ng/mL in controls vs. 84 ng/mL in extract-treated cultures) and tumor necrosis factor alpha (TNF-α) levels (169 ng/mL in controls vs. 32 ng/mL in extract-treated cultures), whereas nterleukin-6 (IL-6) was moderately elevated (from 158 ng/mL in controls to 234 ng/mL in extract-treated cultures) and IL-10 remained low. These findings demonstrate that P. molle extract combines cytotoxic activity against cancer cells with potent immunomodulatory effects, highlighting its potential as a source of bioactive compounds for immune-based therapeutic strategies. Full article

Background: Post-COVID-19 cognitive impairment, commonly referred to as “brain fog,” represents a significant clinical problem, yet its underlying mechanisms remain incompletely understood. New research indicates that long-term cognitive consequences of SARS-CoV-2 infection may result from chronic immunological dysregulation and neurometabolic changes. Objective: We aimed to assess the associations between cognitive performance, cerebral glucose metabolism, and inflammatory markers in patients with COVID-19 brain fog symptoms. Methods: This study included 47 patients with post-COVID-19 cognitive complaints enrolled in the COVMENT trial. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). Brain glucose metabolism was evaluated with FDG PET-CT, and inflammatory markers, including C-reactive protein (CRP), monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, eosinophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were measured. Correlation analyses, logistic regression, and ROC analysis were performed to explore relationships between these factors. Results: A lower score of the MoCA abstraction domain correlated significantly with lower FDG uptake in multiple brain regions, including inferior parietal lobules and precuneus. Among inflammatory markers, only PLR demonstrated significant associations with both brain metabolism and abstraction performance. Lower PLR values were associated with greater neurometabolic impairment, and PLR < 130.1 was associated with abnormal abstraction performance. Conclusions: Post-COVID-19 cognitive dysfunction can be associated with selective neurometabolic alterations in brain regions supporting abstract reasoning. PLR seems to be associated with both cognitive performance and regional brain metabolism, suggesting a potential link between chronic immune dysregulation and neurocognitive impairment in post-COVID-19. Full article

For decades, immunology has followed a clear paradigm: immunological memory resides only within the adaptive immunity, as a unique property of lymphocytes giving the host the ability to recognize specific antigens and offer long-term protection. However, this raises an important question: how valid is this belief in light of new evidence? The discovery of trained immunity shows that innate immune cells can also develop lasting functional changes. This finding prompts a profound reconsideration of the traditional framework. Trained immunity is a functional reprogramming of the innate immune cells driven by long-term epigenetic and metabolic reprogramming, resulting in enhanced responses upon subsequent exposure to the same pathogen or even to unrelated stimuli. The presence of pattern recognition receptors (PRRs) on innate immune cells already suggested a certain level of specificity in this compartment thanks to the engagement of a PRR by a pathogen-associated molecular pattern (PAMP) inducing memory-like properties in the responding cell. While such partial specificity can enhance protection, it may also amplify aberrant inflammatory circuits, thereby contributing to the initiation or worsening of autoimmune and chronic inflammatory diseases. This dual nature of trained immunity raises important questions for the field: is trained immunity ultimately harmful or beneficial in autoimmunity, and can its mechanisms be harnessed therapeutically rather than pathologically? The present Perspective will address these issues by examining recent findings that reveal the specificity, pathogenic potential, and translational opportunities in given examples of autoimmune diseases (ADs). Full article

Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good’s syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk. Full article

Pregnant women undergo a myriad of physiological changes, including important hormonal variations. Pregnancy gingivitis is a condition that affects up to 30% to 100% of women, is related to hormonal modifications, and could play an important role in gestational gut colonization and immunological training of the newborn. Nonetheless, oral health is not always included in routine prenatal care. In this study, we collected saliva samples of pregnant women with and without pregnancy gingivitis and analyzed the oral microbiota through 16S sequencing. In addition, meconium samples from the infants of participating women were analyzed. The oral microbiota of pregnant women with and without pregnancy gingivitis did not show significant differences in diversity. However, significant differences in microbiome composition were observed. Pathway analysis showed that, despite taxonomic similarity, the PG group had activated energy metabolism, bacterial growth, lipid metabolism, and virulence pathways with NOD-like receptor activation, indicating pro-inflammatory microbial activity. In contrast, the NPG group exhibited central metabolism and repair mechanisms, suggesting that PG could affect microbiome function rather than composition. In addition, it appears that the microbiome composition of offspring of mothers with gingivitis also differs from that of offspring from mothers without gingivitis, although the number of available samples did not allow for definite conclusions. As such, a larger cohort and deeper sequencing methods are needed to assess the oral microbiota of pregnant women with and without gingivitis and to explore the possibility of bacterial translocation from the maternal gingiva to the fetal gut. Full article

Background: Lactate accumulation is increasingly recognized as a feature of tumor metabolic reprogramming that can coincide with immune dysregulation and aggressive phenotypes. The prognostic and immunologic relevance of lactate-associated heterogeneity in lung cancer remains to be clarified. Methods: We curated lactate-related genes and identified prognostic candidates in lung cancer cohorts. Consensus clustering was applied to define lactate-associated molecular subtypes, followed by characterization of survival and tumor microenvironment features. A LASSO-based gene signature was developed to generate an individual-level risk score and an integrated nomogram. Multi-omics analyses were used to evaluate concordance between transcriptomic and proteomic alterations. Single-cell transcriptomic data were analyzed to explore cellular heterogeneity in lactate-related programs. In vitro assays evaluated the response of candidate genes to lactate exposure and assessed cell migration and invasion under proliferation-inhibited conditions after genetic perturbation. Results: Two lactate-associated molecular subtypes were identified with distinct overall survival and divergent immune microenvironment features. Subtype 1 was associated with better outcomes and a more immune-inflamed profile, whereas Subtype 2 was associated with poorer outcomes and a myeloid-enriched, immunosuppressive contexture. Pathway analyses indicated subtype-associated differences in extracellular matrix-related processes and apoptosis-associated signaling. We developed an 11-gene prognostic signature and nomogram that stratified patients by risk across TCGA and GEO cohorts. Multi-omics integration highlighted ANLN, FGA, and DKK1 as consistently dysregulated at both transcript and protein levels. Among these candidates, DKK1 showed lactate-responsive induction in vitro. DKK1 perturbation altered lactate-enhanced migratory and invasive phenotypes and was accompanied by changes in intracellular lactate levels and global protein lactylation, supporting a potential feedforward relationship between lactate exposure, DKK1 expression, and lactylation. Conclusions: This study characterizes lactate-associated molecular heterogeneity in lung cancer and provides a lactate-related subtype framework and prognostic risk model for patient stratification. The findings nominate DKK1 as a lactate-responsive candidate linked to migration/invasion phenotypes and lactate/lactylation changes in vitro. Full article

Colorectal cancer (CRC) is traditionally considered a “cold tumor” characterized by low immunogenicity and limited responsiveness to immune checkpoint inhibitors (ICIs). However, recent findings reveal that cytotoxic modalities can reprogram this immunologically inert landscape. This review integrates these evolving concepts to guide the optimization of future treatments. Radiotherapy induces extensive DNA double-strand breaks, which may generate de novo mutations through error-prone repair while simultaneously exposing cryptic antigens via increased transcriptional instability, alternative splicing, and enhanced proteasomal processing. Chemoradiation also amplifies epigenetic and epitranscriptomic sources of neoepitope diversity, including RNA editing and stress-induced splicing alterations, expanding the immunopeptidome beyond canonical mutation-driven neoantigens. These changes collectively enhance antigen presentation and facilitate T-cell priming. Chemotherapy further reduces immunosuppressive cell populations and promotes dendritic cell activation, creating a permissive milieu for subsequent immune engagement. Clinically, the VOLTAGE studies demonstrated that long-course chemoradiotherapy can sensitize even mismatch repair–proficient rectal cancers to PD-1 blockade, yielding clinically meaningful pathological responses. In contrast, mismatch repair–deficient rectal tumors may respond completely to ICIs alone. Short-course radiotherapy combined with chemotherapy and ICIs has also shown encouraging activity in the setting of total neoadjuvant therapy. Collectively, these findings support a paradigm in which radiotherapy, chemotherapy, and epigenetic/epitranscriptomic alterations—including RNA editing—act as potent modulators of tumor antigenicity. By expanding the neoantigen repertoire and reshaping the tumor microenvironment, these strategies can transform CRC from a cold tumor into one that is increasingly responsive to immunotherapy. Full article

Early identification of the risk of malignant transformation in oral potentially malignant disorders (OPMDs) is critical for improving outcomes in oral squamous cell carcinoma (OSCC). This comprehensive review examines immunological biomarkers obtained from minimally invasive oral cytobrush (OCB) specimens for the early detection of OSCC within a precision medicine framework. The objectives were to (1) identify and characterise key immunological biomarkers associated with early oral carcinogenesis; (2) evaluate the diagnostic utility of OCB sampling for detecting these biomarkers; and (3) explore the potential of OCB-based profiling to support personalised screening and patient management. The review highlights the potential advantages of OCB compared with conventional diagnostic methods, as reported in the literature, particularly its ability to capture early malignant changes through immunological analysis. Evidence is discussed for biomarker pathways related to cell-cycle and differentiation dysregulation (p53, Ki-67, CKs), inflammation-driven epithelial transformation (IL-1β, IL-6, IL-8, TNF-α), and immune suppression and checkpoint activation (PD-L1, B7-H6). OCB provides reliable and patient-friendly cyto-salivary samples that are suitable for immunological and molecular analyses. Aberrant biomarker expression detected in OCB specimens correlates with epithelial dysplasia and reflects early non-invasive neoplastic transformation, supporting the diagnostic value of integrated biomarker panels. Overall, OCB-based immunoanalysis represents a practical, non-invasive approach for the early detection of OSCC. Emerging technologies, including AI and multi-omics approaches, may further support the precision and predictive values of immunological analysis for OSCC. When combined with relevant biomarker pathways reflecting tumour biology and host immune responses, this strategy could offer a strong foundation for precision-medicine screening. It may also support personalised monitoring in patients with OPMDs. Full article

Eisenia fetida is one of the soil invertebrates most used in ecotoxicological and ecopathological studies. To date, the potential contribution of naturally occurring parasites to the variability of ecotoxicological endpoints has been poorly investigated. In this study, we provide a detailed histological description of the male reproductive system of E. fetida and report the occurrence and histological alterations associated with Monocystis sp. infection in laboratory-reared individuals. Uninfected individuals exhibited complete spermatogenesis, with all developmental stages from spermatogonia to mature spermatozoa and normal sperm storage within the spermathecae. Meanwhile, infected earthworms displayed marked reproductive alterations, including reduced sperm production and diminished sperm retention within spermathecae. Multilayered encapsulations, inflammatory nodules and melanization were detected within the seminal vesicles, in contrast with the immunological evasion observed in Lumbricus terrestris. These findings suggest species-specific differences in immune response and indicate that Monocystis sp. infection can induce reproductive impairment and activate energy-consuming immune responses. Because these parasite-induced changes closely resemble pollutant-driven ecotoxicological effects, Monocystis infections may act as a potential bias in ecotoxicological studies. We therefore recommend implementing parasitological screening of laboratory cultures to ensure the reliability of studies employing E. fetida as a bioindicator. Full article

Background and Objectives: Hyaluronic acid (HA) is extensively used in dermo-aesthetic medicine for its hydrating and tissue-repairing properties. Beyond cosmetic use, HA has shown therapeutic effects in inflammatory skin diseases such as seborrheic, radiation-induced, and atopic dermatitis (AD). However, HA-based aesthetic formulations such as Profhilo^®, a hybrid complex of high- and low-molecular weight HA, have not been tested in immunologically driven models of AD. This study aimed to investigate the therapeutic effects of intradermal Profhilo^® injections in a recently developed ovalbumin (OVA)-induced murine model of AD. Specific objectives included assessing changes in skin inflammation, pain sensitivity, and spinal cord pathology. Materials and Methods: Twenty-eight adult female ICR-CD1 mice were sensitized and exposed to OVA via intraperitoneal, subcutaneous, and topical routes over 49 days to induce AD-like lesions. Control animals received saline. On day 50, mice were subdivided into four groups receiving intradermal injections of Profhilo^® or saline. Skin inflammation was evaluated using the SCORAD index on days 49 and 57, and nociceptive responses were measured using the plantar thermal hyperalgesia test. On day 57, dorsal skin and thoracic spinal cord samples were collected for histological and immunohistochemical analysis, including assessments of epidermal and dermal thickness, mast cell density, collagen content, CGRP immunoreactivity, and microglial activation. Results: OVA-treated mice developed significant skin inflammation (p < 0.0001) and thermal hyperalgesia. Intradermal HA injection significantly reduced SCORAD scores (p < 0.01) and mast cell density (p < 0.05) while increasing dermal thickness (p < 0.05). In the spinal cord, HA treatment reduced CGRP immunoreactivity and microglial activation (p < 0.01 and p < 0.05, respectively), especially in OVA-treated animals. Conclusions: Intradermal Profhilo^® alleviated both cutaneous inflammation and neurogenic pain in an OVA-induced AD model. These findings suggest that HA not only improves local skin pathology but also modulates central neuroimmune responses, supporting its therapeutic potential for inflammatory skin conditions involving peripheral and central sensitization. Full article

Background/Objectives: Physical exercise reduces breast cancer (BC) risk and improves survival, yet the biological mechanisms remain incompletely understood. Exercise may modulate systemic immunity and local immune cell infiltration in the tumor microenvironment. In this systematic review and meta-analysis, we examined the effects of exercise on immune cells and immune-related markers in patients with BC. Methods: This study followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251082444). Four databases (PubMed, Web of Science, Scopus, and Cochrane Library) were searched from inception through December 2025. Randomized controlled trials evaluating exercise interventions in patients with BC or BC survivors and reporting immune cell outcomes were included. Meta-analyses were performed on studies reporting natural killer cells, natural killer cell activity, T-cell subpopulations, and B cells. Results: A total of 18 studies involving 911 participants (539 in exercise intervention groups) were included in the systematic review, with eight studies included in meta-analyses. Exercise interventions did not show significant effects on circulating natural killer cell counts, natural killer cell activity, T-cell subpopulations (CD3⁺, CD4⁺, and CD8⁺), or B-cell levels when compared to control groups. Conclusions: Exercise does not appear to induce consistent changes in resting circulating immune cell populations in patients with BC or BC survivors, indicating that exercise is immunologically safe while potentially exerting effects beyond circulating cell counts. Further large-scale research is required. Full article

West Nile Virus (WNV) is becoming a significant and enduring public health menace in Europe, propelled by climate changes and accelerated population aging. Most infections are asymptomatic but older adults are more prone to develop neuroinvasive disease, which is characterized by high morbidity and mortality, as well as long-term neurological disturbances and disability. To date, there is still no licensed human vaccine or specific antiviral treatment, and management is mostly supportive. This review brings together the most recent information about WNV epidemiology, pathogenesis, and clinical manifestations, with a special focus on older people in Europe. We critically analyze current and novel pharmaceutical strategies, encompassing drug repurposing, nucleoside analogues, interferon-based therapies, peptides, monoclonal antibodies, and host-directed agents, emphasizing their therapeutic potential alongside the challenges presented by age-related pharmacokinetic and immunological alterations. We also discuss some important gaps in the current evidence base, such as the frequent exclusion of older adults from clinical studies and the lack of a coordinated clinical trial infrastructure that can be quickly activated during seasonal outbreaks. Lastly, we suggest a framework that combines systematic antiviral screening with the creation of a Europe-wide network of clinical trial readiness that is built into current One Health surveillance systems. Full article

Wildfires have emerged as a critical environmental and public health challenge globally, with their rising frequency and severity largely attributed to climate change. Although wildfire smoke is well recognized for its detrimental effects on respiratory and cardiovascular health, a growing body of evidence indicates that its immunological impacts are equally consequential. Composed of a complex mixture of particulate matter, volatile gases, and organic chemicals, wildfire smoke can disrupt immune homeostasis through multiple, interconnected pathways. Recent findings underscore the susceptibility of natural killer (NK) cells—key effectors of the innate immune system—to wildfire smoke-induced dysregulation. This review synthesizes current knowledge on the immunotoxicological effects of wildfire smoke with a specific focus on NK cell biology. It examines how both acute and chronic smoke exposures alter NK cell frequency, phenotype, and cytotoxic function, and explores the mechanistic contributions of inflammation, oxidative stress, and pollutant-mediated receptor modulation. Furthermore, the review considers potential long-term consequences of NK cell impairment, including heightened vulnerability to viral infections, diminished tumor surveillance, and broader disruptions in innate–adaptive immune crosstalk. Collectively, the evidence highlights the need for targeted research to delineate the pathways by which wildfire smoke compromises NK cell-mediated immunity and to inform strategies for mitigating these risks in exposed populations. Full article