Search Results (6,034)

Background/Objectives: Human breast milk is a biologically active fluid. It contains immune cells, stem cells, epithelial cells, and lactocytes. These components may support infant development and immune defense. While milk composition is known to vary with physiological and nutritional factors, the impact of the home environment remains poorly understood. The aim of this study was to examine how selected conditions affect the cellular composition of breast milk. Methods: We conducted a cross-sectional study involving 49 lactating mothers of healthy infants under 6 months of age. Breast milk samples were analyzed using flow cytometry. We measured proportions of immune cells (CD3⁺, CD4⁺, CD8⁺, CD19⁺, and CD16/56⁺), hematopoietic stem cells (CD34⁺), mesenchymal stem cells (CD105⁺, CD73⁺, and CD44⁺), and lactocytes (CD326⁺ CD73⁺ and CD326⁺ CD73⁻ phenotypes). Participants completed a questionnaire assessing number of children, co-sleeping, pet ownership, and number of household members. Results: Mothers with more than one child showed higher percentages of CD4⁺ (p = 0.047) and CD8⁺ (p = 0.031) T cells and fewer CD73⁺ lactocytes (p = 0.028). Co-sleeping was associated with lower levels of CD3⁺ T cells in milk (p = 0.021). Pet ownership correlated with a lower proportion of cytotoxic CD8⁺ cells (p = 0.048). The number of household members had no significant effect. Conclusions: Domestic factors such as number of children, co-sleeping, and pet exposure are associated with shifts in the immune and lactocyte cell composition of breast milk. These findings suggest that breast milk dynamically adapts to maternal and household-level immune stimuli. Full article

Background/Objectives: Axial spondyloarthritis (axSpA) is a chronic immune-mediated inflammatory disorder affecting the spine and sacroiliac joints, with variable clinical expression. This study assessed serum levels of inflammatory (TNF-α, IL-17A) and metabolic (leptin, adiponectin) biomarkers and their associations with disease activity, inflammation, structural damage, and comorbidities. Methods: This prospective cross-sectional study assessed 89 axSpA patients using clinical, laboratory, and radiological evaluations. Disease activity was measured using ASDAS-CRP and BASDAI scores. Radiographic damage was quantified using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Serum concentrations of TNF-α, IL-17A, leptin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical and imaging correlations were analyzed. Results: Serum leptin levels correlated significantly with higher disease activity scores, inflammatory markers (CRP, ESR), radiographic progression (syndesmophyte formation, mSASSS), and arterial hypertension. Adiponectin levels were inversely associated with disease activity, structural damage, and arterial hypertension, suggesting anti-inflammatory, bone- and cardio-protective properties. TNF-α levels showed an association with inflammatory markers and were higher in patients with peripheral enthesitis. IL-17A levels were weakly correlated with disease activity and structural severity and were significantly lower in patients with a history of anterior uveitis. Conclusions: Leptin and adiponectin may serve as complementary biomarkers in axSpA, reflecting both inflammatory burden and structural damage. While TNF-α and IL-17A remain key therapeutic targets, their correlation with structural changes appears limited. Biomarker profiling could support personalized disease monitoring. Longitudinal studies are needed to validate prognostic implications. Full article

Background: Varicella remains a prevalent vaccine-preventable disease, but breakthrough infections are increasingly reported. However, long-term, population-based studies investigating the temporal and demographic characteristics of breakthrough varicella remain limited. Methods: This retrospective study analyzed surveillance data from Jinhua City, China, from 2016 to 2024. Varicella case records were obtained from the China Information System for Disease Control and Prevention (CISDCP), while vaccination data were retrieved from the Zhejiang Provincial Immunization Program Information System (ISIS). Breakthrough cases were defined as infections occurring more than 42 days after administration of the varicella vaccine. Differences in breakthrough interval were analyzed across subgroups defined by dose, sex, age, population category, and vaccination type. A bivariate cubic regression model was used to assess the combined effect of initial vaccination age and dose interval on the breakthrough interval. Results: Among 28,778 reported varicella cases, 7373 (25.62%) were classified as breakthrough infections, with a significant upward trend over the 9-year period (p < 0.001). Most cases occurred in school-aged children, especially those aged 6–15 years. One-dose recipients consistently showed shorter breakthrough intervals than two-dose recipients (M = 62.10 vs. 120.10 months, p < 0.001). Breakthrough intervals also differed significantly by sex, age group, population category, and vaccination type (p < 0.05). Regression analysis revealed a negative correlation between the initial vaccination age, the dose interval, and the breakthrough interval (R² = 0.964, p < 0.001), with earlier and closely spaced vaccinations associated with longer protection. Conclusions: The present study demonstrates that a two-dose varicella vaccination schedule, when initiated at an earlier age and administered with a shorter interval between doses, provides more robust and longer-lasting protection. These results offer strong support for incorporating varicella vaccination into China’s National Immunization Program to enhance vaccine coverage and reduce the public health burden associated with breakthrough infections. Full article

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine. Full article

Genomes of animals harbor not only homozygous (ROH) but also HRR segments of chromosomes. In the current study, the HRRs in Holstein cattle were analyzed using a 50K array. On average, 366 Holstein cows from six herds had 439 ± 7 and 111 ± 3 HRRs per cow when HRRs with a minimum length of 50 kb and 250 kb were detected, respectively. The average HRRs values did not differ between herds. Removal of SNP with an MAF less than 0.01 leads to a noticeable increase in the number of HRRs. The distribution of HRRs in the chromosomes of cows is not uniform and depends on the scanned lengths of the HRR segments. No clear correlations were found between interchromosomal HRR specific density and the occurrence of HRRIs. When HRR segments with a length of 50 kb or more have been detected, the significant HRRIs were located on BTA1, BTA10, BTA20, and BTA21(first set); for HRR segments with a length of 250 kb or more, significant islands were found on BTA9, BTA11, and BTA29 (second set). According to the Tajima D test, the islands on the BTA of the first set have maximum values of 3.47–2.82, while the islands on the BTA of the second set have values of less than 2.49. The genes in the HRRIs are involved in immune response, oogenesis, and reproduction but are not related to milk production traits. These results show that the recognition of HRRIs strongly depends on the length of the scanned HRR segments. No single “mechanism” was identified as the main cause of HRRIs. Full article

Background/Objectives: The whole cell pertussis vaccine was introduced in the United States in the 1940s and switched to the acellular pertussis vaccine partially in 1992 and completely in 1997. This study examines the relationship between the resurgence of pertussis in the United States and the change in the type of pertussis vaccines. Methods: Pertussis cases from 1922 to 2024 were obtained from the CDC’s national notifiable disease surveillance system, and vaccination coverage was obtained from the WHO. A trend analysis and Pearson’s correlation test were conducted between the incidence of cases and the coverage of the third and fourth doses of the pertussis vaccine. An ANOVA test and multivariable linear regression were performed to assess the association between the type of vaccine and the number of pertussis cases. Results: The number of cases increased from 4083 in 1992 to 35,435 in 2024, with cyclical outbreaks in 2010, 2012–2014, and 2024. The third and fourth doses of pertussis vaccine coverage had mild and moderate correlations with the number of pertussis cases. The vaccine type had a significant association with the number of pertussis cases and stayed significant after adjusting for vaccination coverage. Conclusions: The switch in pertussis vaccine has impacted the epidemiology of pertussis outbreaks in the United States. A combination of factors, such as different types of immune response to vaccines, waning of immunity, and selection of non-vaccine bacterial strains, may explain the observed results. Further research on newer, improved vaccinations or alternative schedules in children needs to be conducted to address the resurgence of pertussis in this study. Full article

Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article

Streptococcus pyogenes (Group A Streptococcus, StrepA) is a human pathogen responsible for hundreds of millions of infections each year and remains one of the most prevalent bacterial causes of upper respiratory and skin infections worldwide. Despite its global impact, there is no approved vaccine, and the optimal protective immune response is still not fully understood. In particular, the role of Th17 T cells in immunity against StrepA remains to be explored. We have previously shown that Th17 T cells are induced in humans following StrepA infection. In this study, we investigated the role of Th17 T cells during skin and upper airway StrepA infections. To generate StrepA-specific Th17 T cells, we utilized a novel cationic liposomal adjuvant system. We demonstrated that vaccine-induced Th17 T cells are recruited to the skin and upper airways upon StrepA infection. In the airways, Th17 T cells and IgA correlate with protection, whereas Th1 T cells and IgG do not. To further characterize the recruited Th17 T cells, we used an IL-17 fate-reporter mouse model to track Th17 T cells. Our results show that Th17 T cells outnumber bona fide Th1 T cells in both StrepA-infected skin and upper airways. Surprisingly, most Th17 T cells lose expression of IL-17, and do not express TNFα, IFNγ, and IL-2. Initial single-cell sequencing data suggest the existence of multiple Th17 T cell subsets with distinct expression profiles. We discuss the functional relevance of these subsets in the context of a StrepA infection. Full article

IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide new knowledge of the mechanisms responsible for the immune adaptation of the fetus to extrauterine life. FcGBP concentrations were measured by ELISA in the first-pass meconium and amniotic fluid samples collected from 120 healthy neonates delivered by either vaginal birth (n = 35) or cesarean section (n = 85) at 36 to 41 weeks gestation. The meconium FcGBP concentrations (405.78 ± 145.22 ng/g) decreased (r = −0.241, p = 0.007) over the course of 36 to 41 weeks gestation, but there were no significant changes (p > 0.05) in the amniotic fluid FcGBP (135.70 ± 35.83 ng/mL) in the same period. Both meconium and amniotic fluid FcGBP concentrations were higher (p < 0.05) in neonates delivered by cesarean section. Decreases in the meconium FcGBP concentrations correlated (r = −0.37, p = 0.027) with the gestational age in neonates delivered by vaginal birth but not in those delivered by cesarean section (p > 0.05). No association was found between the FcGBP concentrations in meconium and amniotic fluid and the birth weight (p > 0.05). With the development of the mucosal immune system in the fetal intestine over the course of the third trimester of gestation, the meconium FcGBP concentrations decrease. Increased FcGBP concentrations measured in the meconium and amniotic fluid of neonates delivered by cesarean section may possibly indicate altered intestinal mucosal function. Intrauterine growth is not associated with the intestinal mucosal barrier maturation involving FcGBP. Full article

Background: RiBi is integral to cell proliferation, and its dysregulation is increasingly recognized as a hallmark of aggressive cancers. We sought to develop and validate a composite “PanRibo-515 score” reflecting RiBi activity across multiple tumor types, assess its prognostic significance, and explore its relationship with immune checkpoint therapy outcomes. Methods: We curated 515 RiBi–associated genes (PanRibo-515) and used a LASSO regression-based strategy on a training dataset (GSE202203) to select the prognostically most relevant subset of 68 genes (OncoRibo-68). Directionality (positive or negative impact on survival) was assigned based on the sign of the LASSO coefficients. We integrated a forward selection approach to identify a refined subset of genes for computing the OncoRibo-68 score. For validation, patients in The Cancer Genome Atlas (TCGA) were stratified into high or low OncoRibo-68 score groups for survival analyses. Additional validation for immunotherapy response was conducted using bioinformatic platforms used for immunotherapy response analysis. Results: A higher OncoRibo-68 score consistently correlated with poorer overall and progression-free survival across multiple cancers. Elevated OncoRibo-68 score was linked to an immunosuppressive tumor microenvironment, but interestingly to increased response to checkpoint inhibitors. Conclusions: Our findings highlight RiBi as an important determinant of tumor aggressiveness and identify the OncoRibo-68 score as a promising biomarker for risk stratification and therapy selection. Future research may evaluate whether targeting RiBi pathways could enhance treatment efficacy, particularly in combination with immunotherapy. Full article

Multiple sclerosis (MS) and allergic diseases, traditionally considered immunologically opposing entities, may share pathogenic mechanisms rooted in immune dysregulation. While MS is predominantly mediated by Th1 and Th17 responses and allergies by Th2 responses, emerging evidence suggests overlapping immunological pathways, including the involvement of histamine, regulatory T cells, and innate lymphoid cells. This review synthesizes current knowledge on the epidemiological and immunopathological associations between MS and allergies. Epidemiological studies have yielded inconsistent results, with some suggesting a protective role for respiratory and food allergies against MS onset, while others find no significant correlation. Clinical studies indicate that food allergies in adults may be associated with increased MS inflammatory activity, whereas childhood atopy might exert a protective effect. In addition, we review hypersensitivity reactions to disease-modifying treatments for MS, detailing their immunological mechanisms, clinical presentation, and management, including desensitization protocols where applicable. Finally, we explore how treatments for allergic diseases—such as clemastine, allergen immunotherapy, montelukast, and omalizumab—may modulate MS pathophysiology, offering potential therapeutic synergies. Understanding the interplay between allergic and autoimmune processes is critical for optimizing care and developing innovative treatment approaches in MS. Full article

Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC. Full article

This study assessed the seroprevalence of anti-Anisakis simplex antibodies in Norwegian patients with inflammatory bowel disease (IBD), specifically ulcerative colitis (UC) and Crohn’s disease (CD), compared with healthy controls. Associations between anti-A. simplex antibody positivity and clinical or laboratory parameters in IBD were also explored. A total of 86 UC patients, 68 CD patients, and 41 healthy controls were prospectively enrolled from four Norwegian hospitals (2013–2022). Diagnosis and disease activity were established using standard clinical, endoscopic, and biomarker criteria. Serum samples were analyzed for total Ig, IgG, IgM, IgA, and IgE antibodies against A. simplex and Pseudoterranova decipiens using ELISA. Anti-A. simplex IgG seroprevalence was 4.9% in controls and 3.2% in IBD (3.5% UC, 2.9% CD). IgM seroprevalence was 0% in all groups. IgA seroprevalence was higher in IBD (16.2%) than controls (4.9%), with 14.0% in UC and 19.1% in CD. IgE seroprevalence was low across all groups. Smoking correlated with lower antibody levels and higher surgery rates. In UC, higher anti-A. simplex IgG and IgE levels were associated with milder disease and better prognosis. Anti-TNFα and azathioprine treatments were linked to higher anti-A. simplex IgA. Norwegian UC and CD patients had significantly higher anti-A. simplex total Ig and IgA seroprevalence than healthy controls, indicating increased exposure or immune response. Anti-A. simplex IgG and IgE may serve as markers of clinical activity in UC. Further research is warranted to clarify the clinical significance of these findings. Full article

Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, and peripheral blood cell-based biomarker. Methods: The present study represents a retrospective observational analysis carried out within a single-center setting. Ninety-five patients with PM stages I–IV were enrolled in the study. We analyzed the correlation between patients’ demographic characteristics, clinicopathological factors such as histological subtypes, surgery status, tumor thickness, blood-based parameters, and treatment options with their prognoses. PIV was calculated by the following formula: (neutrophil count × monocyte count × platelet count)/lymphocyte count. Additionally, blood-based parameters were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). Results: We categorized the patients into two groups, low PIV group (PIV ≤ 732.3) and high PIV group (PIV > 732.3) according to the determined cut-off value, which was defined as the median. It was revealed that high PIV was associated with poor survival outcomes. The median follow-up period was 15.8 months (interquartile range, IQR, 7.1 to 29.8 months). The median overall survival (OS) was significantly longer in patients in the low PIV group (median 29.8 months, 95% confidence interval (CI), 15.6 to 44) than the high PIV group (median 14.7 months, 95% CI, 10.8 to 18.6 p < 0.001). Furthermore, the study revealed that patients with low PIV, NLR, and SII values were more likely to be eligible for surgery and were diagnosed at earlier stages. Additionally, these markers were identified as potential predictors of disease-free survival (DFS) in the surgical cohort and of treatment response across the entire patient population. Conclusions: In addition to well-established clinical factors such as stage, histologic subtype, resectability, and Eastern Cooperative Oncology Group (ECOG) performance status (PS), PIV emerged as an independent and significant prognostic factor of overall survival (OS) in patients with PM. Moreover, PIV also demonstrated a remarkable independent prognostic value for disease-free survival (DFS) in this patient population. Additionally, some clues are provided for conditions such as treatment responses, staging, and suitability for surgery. As such, in this cohort, it has outperformed the other blood-based markers based on our findings. Given its ease of calculation and cost-effectiveness, PIV represents a promising and practical prognostic tool in the clinical management of pleural mesothelioma. It can be easily calculated using routinely available laboratory parameters for every cancer patient, requiring no additional cost or complex procedures, thus facilitating its integration into everyday clinical practice. Full article

Background/Objectives: Acute pancreatitis (AP) is a highly variable inflammatory condition that can lead to severe complications and high mortality, particularly in its severe forms. Early risk stratification is essential; however, the delayed availability of traditional scoring systems often limits its effectiveness. This study aimed to evaluate the clinical utility of systemic inflammation indices as early predictors of severity in patients with acute pancreatitis. Methods: A retrospective, observational study was conducted among patients diagnosed with acute pancreatitis, classified according to the revised Atlanta criteria. Upon admission, systemic inflammation indices were calculated from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). Severity was assessed using the APACHE II score. Statistical analysis involved Kruskal–Wallis tests, Dunn’s post hoc comparisons, ROC curve analysis, logistic regression for odds ratios (ORs), and Spearman correlations. Results: SII, NLR, MLR, SIRI, and AISI showed statistically significant associations with AP severity (p < 0.05). MLR and SIRI exhibited the highest predictive performance (AUC = 0.74). ORs for severe pancreatitis were: MLR = 19.10, SIRI = 7.50, NLR = 7.33, AISI = 5.12, and SII = 4.10. All four indices also demonstrated moderate positive correlations with APACHE II scores. Conclusions: Systemic inflammation indices are simple, cost-effective, and accessible tools that can aid in the early identification of patients at high risk for severe acute pancreatitis. Their integration into clinical practice may enhance early decision-making and improve patient outcomes. Full article