Search Results (459)

Galectin-3 (Gal-3) is a multifunctional molecule that exerts pleiotropic effects in inflammatory responses and contributes to the pathogenesis of numerous immune-mediated diseases. Although Gal-3 has been known for more than five decades, it remains a lectin with intriguing and not yet fully elucidated properties. The existing body of evidence underscores the importance of Gal-3 in the regulation of homeostatic and inflammatory processes. Neurotrophins are traditionally recognized as key regulators of neuronal development, survival, and synaptic plasticity; nevertheless, accumulating evidence indicates that they also play important roles in immune regulation and neuroimmune communication. Importantly, neurotrophins are also produced by immune cells, including monocytes, macrophages, lymphocytes, and basophils, which express functional neurotrophin receptors including tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase A (TrkB), and p75 neurotrophin receptor (p75NTR). In this narrative review, we synthesize current evidence on neuroinflammation, neurotrophins, and Gal-3, with a particular focus on the molecular mechanisms involved in the crosstalk between neurotrophins and Gal-3 or immune cells. We further examine how this neuroimmune–neurotrophic crosstalk contributes to the pathogenesis of psychiatric and neurodegenerative disorders, as well as other neurological conditions. Finally, we discuss the emerging therapeutic potential of targeting neurotrophins and Gal-3 as modulators of neuroinflammation. Full article

Immune thrombocytopenia (ITP) is an autoimmune disease. Megakaryocyte dysfunction caused by autoimmune response can lead to thrombocytopenia, and the underlying mechanism is still unclear. Single-cell sequencing analysis revealed the heterogeneity of CD34 + HSPCs in bone marrow between ITP patients and healthy groups. Pre-B cell population 1 (pre-B1) showed a significantly lower percentage contribution in ITP groups, and the underlying mechanism involves cell cycle-, cell apoptosis- and cell death-related pathways. The number of eosinophil–basophil mast cell progenitors (EBMPs) is significantly increased in ITP patients and the DEGs of the EBMPs in ITP patients were significantly enriched in immune-related pathways. Further, immunofluorescent staining and Western blot assay highlight C-X-C Motif Chemokine Ligand 8 (CXCL8) and Interferon Regulatory Factor 1 (IRF1) expression were significantly increased in the EBMPs of ITP patients. Furthermore, cell–cell communication analysis identified an impaired LGALS9-CD44 axis between EBMP cells and MkP1 cells in ITP patients, suggesting that targeting the LGALS9-CD44 interaction might hold promise as a therapeutic approach for ITP. Our observations indicate that ITP patients exhibit an elevated proportion of EBMP cells alongside a reduced proportion of pre-B1 cells. CXCL8 and IRF1 are potentially associated with EBMP cell dysfunction and the ITP disease process. Furthermore, the diminished LGALS9-CD44 axis between EBMP and MkP1 cells may contribute to ITP progression, suggesting a direction for future therapeutic investigation. Full article

Aim: The identification of alcohol and substance use disorders is primarily based on clinical evaluation, and the lack of accessible objective markers remains a challenge. This study aimed to explore whether routine hemogram parameters, analyzed using multiclass machine learning models, could assist in differentiating individuals with alcohol use disorder, substance use disorder, and healthy controls. Method: This retrospective case–control study included 35 patients with alcohol use disorder, 61 patients with substance use disorder, and 132 healthy controls. Routine hematological parameters were obtained from hospital records. Multiclass classification models, including Random Forest, Support Vector Machine (SVM), Artificial Neural Network (ANN), and other conventional machine learning algorithms, were applied. Model performance was evaluated using 10-fold cross-validation with metrics including accuracy, sensitivity, precision, F1-score, and AUC. Results: Significant differences were observed among groups in several hematological parameters, including monocyte count, basophil count, and RDW-CV (p < 0.05). Among the models, Random Forest achieved the highest overall accuracy (81.6%) and AUC (0.93), followed by SVM and ANN models with comparable performance. However, classification performance was not uniform across all classes, and sensitivity was relatively lower for the alcohol use disorder group compared to the control and substance use disorder groups. Conclusions: These findings suggest that machine learning models based on routine hemogram parameters may provide a preliminary, low-cost, and accessible supportive approach for differentiating addiction-related conditions. However, the results should be interpreted as exploratory, given the retrospective single-center design, limited sample size, lack of external validation, and absence of model interpretability analyses. Further studies incorporating larger multicenter datasets, confounding factors, and explainable artificial intelligence methods are required before clinical application can be considered. Full article

Background/Objectives: Corneal endothelial cells (CEnCs) exist on the inner surface of the cornea and regulate its hydration. The immune system cannot penetrate CEnCs easily because the cornea is avascular and anterior chamber-associated immune deviation suppresses the immune reaction. Nevertheless, inflammatory cells can infiltrate through the corneal stroma and anterior chambers, and corneal endothelial inflammation can occur. In this cross-sectional study, we investigated the association between the neutrophil-to-lymphocyte ratio (NLR) and human corneal endothelial cells (CEnCs). Methods: A total of 307 eyes from 307 subjects who underwent specular microscopy were included. Corneal endothelial cell density (CECD), hexagonality (HEX), central corneal thickness (CCT), coefficient of variation (CV), and cell area were measured preoperatively using specular microscopy. Whole blood samples were obtained to measure the complete blood cell count. The NLR was calculated, and its relationship with CEnCs was evaluated. Results: In all subjects, CV was positively correlated with the percentage (%) of neutrophils (r = 0.120, p = 0.037) and absolute neutrophil count (r = 0.131, p = 0.022) and negatively correlated with the % of lymphocytes (r = −0.131, p = 0.022). HEX was correlated with the % of neutrophils (r = −0.156, p = 0.006), % of lymphocytes (r = 0.141, p = 0.014), % of basophils (r = 0.142, p = 0.013), the NLR (r = −0.129, p = 0.024), and the mean corpuscular volume (r = 0.121, p = 0.035). Conclusions: CV and HEX, which indicate the stability of CEnCs, are associated with NLR in the peripheral blood, suggesting that systemic inflammation and immunity may implicate in the pathology of CEnCs. Full article

Pregnancy loss affects ~15% of couples and often results from embryonic chromosomal abnormalities. Early peripheral biomarkers that signal abnormal development could improve counseling and clinical decision-making. Here, we analyzed early-pregnancy peripheral blood from patients who conceived via assisted reproduction without preimplantation aneuploidy testing. Samples were collected ≤12 weeks’ gestation for complete blood counts with differentials and multiparameter flow cytometry to quantify major lymphocyte subsets (total T, B, cytotoxic T cells, T helpers (Th), Th1, Th2, Th9, Th17, and regulatory T cells (Treg)). Participants were followed until pregnancy resolution (live birth, euploid or aneuploid miscarriage), and immune profiles were compared by outcome using the Kruskal–Wallis test. Exploratory discriminative analyses were performed with significantly different immune cell quantities. Basophils were highest in the aneuploid miscarriage group (n = 26), distinguishing them from both euploid miscarriage (n = 27) and live birth (n = 91). Th9 cells were lower in aneuploid miscarriages compared to euploid miscarriages. Th17 levels were higher in live births compared with both miscarriage groups. Additional aneuploidy-type-specific immune differences were observed. These alterations may reflect maternal immune recognition of a non-viable conceptus and localized immune activation at the fetal–maternal interface. If validated in larger cohorts, these early peripheral markers may help identify pregnancies at risk for miscarriage, particularly those involving chromosomal abnormalities. Full article

Objective: To investigate the epidemiology, clinical characteristics, and potential risk factors of chronic cough following SARS-CoV-2 infection. Methods: A total of 1434 patients with post-COVID-19 cough were categorized into acute, subacute, and chronic subgroups by cough duration, with clinical data analyzed across subgroups. Questionnaire surveys were conducted in chronic cough patients, followed by an 18–21-month follow-up. Results: 1. Significant intergroup differences were observed among the three groups in: the number of patients with rhinitis and/or pharyngitis history, cough with chest tightness, cough with pharyngeal symptoms, and sensitivity to irritating odors and cold air. 2. The chronic group had a significantly lower platelet count but higher eosinophil and basophil percentages than the acute group. 3. The chronic group showed significantly lower values than the subacute group in multiple pulmonary function indices: FVC, FEV1, FEV1/FVC, PEF, MEF25, MEF75, MEF50, MMEF75/25, MEF75%, MEF50%, MEF25%, MMEF75/25%, DLCO, and DLCO%. 4. Chest CT findings: the chronic group had significantly lower rates of infected lesions, cord-like opacities, and ground-glass shadows than the acute group, but a higher rate of micro-nodules than the subacute group. 5. At follow-up, the cough and non-cough groups differed significantly in nighttime cough scores and the proportion of cough with chest tightness, as well as in pulmonary function parameters: FVC, FEV1, PEF, PEF%, MEF75, DLCO, RV% and TLC. 6. Binary logistic regression analysis identified the nocturnal cough symptom score and cough accompanied by chest tightness as independent factors influencing persistent cough 18–21 months after SARS-CoV-2 infection. Conclusions: Patients with pre-existing upper airway inflammation, laryngeal symptoms, chemical hypersensitivity, elevated eosinophil/basophil percentages, and pulmonary micro-nodules are more likely to develop chronic post-COVID cough, presenting with partial ventilatory impairment and diffusing capacity impairments. Full article

Having appropriate and meaningful diagnostic procedures is crucial in the approach to patients with chronic spontaneous urticaria (CSU), so we wanted to investigate relationships between CSU patients’ common serum factors and clinical CSU features, and their temporal trends during antihistamine treatment. In this exploratory hypothesis-based study, we assessed disease severity and quality of life (QoL) in, initially, 41 CSU patients using UAS7, daily UAS, UCT, DLQI, and CU-Q2oL. Concurrently, we measured serum complete blood count (CBC), total IgE, thyroid antibodies and hormones, ANA, D-dimer, vitamin D, and the inflammatory molecules CRP, ESR and IL-6. We compared initial (T1) and follow-up findings (T2) (after 3 months of antihistamine therapy). Basophil concentration was the only examined serum factor useful in assessing current CSU severity/daily UAS (sensitivity 78.6%; specificity 63%; p = 0.028). Basopenia was more frequent in patients with moderate/severe CSU than in those with mild disease or remission, as measured by daily UAS (79% vs. 37%; p = 0.020). T4 values showed a significant dependence on CSU duration (r = −0.328; p = 0.036). ESR was the only examined serum factor significantly associated with weekly CSU severity (UAS7) (p = 0.038). Antihistamine treatment significantly reduced CSU activity (recorded by daily UAS and UAS7) and improved QoL (DLQI) (p = 0.006) and disease control/UCT (p = 0.005). After three months of treatment, only the CRP value correlated with CSU control/UCT (p = 0.014). We encourage the use of diagnostics employing basophil counts and clinical indices UAS7, daily UAS, UCT and DLQI for insight into a patient’s CSU clinical condition. Serum factor values did not change during the 3-month treatment period, so it is not useful to measure them repeatedly. Although this study involved a small cohort and has many limitations, these promising results highlight the need for replication with a greater number of CSU patients. Full article

Peanut allergy (PA) remains a major diagnostic challenge in pediatric allergy, largely due to the frequent discrepancy between immunological sensitization and clinically relevant disease. This study aimed to develop a real-life diagnostic prediction model to distinguish true peanut allergy from asymptomatic peanut sensitization in children referred for evaluation of suspected PA. In this cross-sectional study, 80 children aged 1–18 years were assessed in a tertiary allergy center in Poland. Sixty-five children with peanut sensitization underwent detailed clinical history assessment, skin prick testing, measurement of serum specific IgE including component-resolved diagnostics, basophil activation testing, and oral food challenges where clinically indicated. Clinically confirmed peanut allergy was diagnosed in 42 sensitized children. In univariate analyses, several clinical and immunological factors were associated with PA, including atopic comorbidities, peanut component sensitization, and basophil activation. Multivariate analysis identified food-induced anaphylaxis and walnut sensitization as independent factors associated with PA. In addition, a penalized diagnostic prediction model was developed to support clinical risk stratification. A multivariable diagnostic prediction model integrating clinical history and laboratory parameters demonstrated good discriminative performance in internal validation (area under the ROC curve 0.83). In conclusion, peanut allergy in sensitized children is determined by a combination of clinical and immunological factors rather than a single biomarker. Integrative diagnostic models may support risk stratification and help optimize the use of oral food challenges in specialized clinical settings, although external validation is required before broader implementation. Full article

Food allergies (FA) are a major public health concern in both children and adults. Immunoglobulin E (IgE)-mediated FA is characterized by allergic reactions driven by allergen-specific IgE and the subsequent degranulation of mast cells and basophils. Current FA management primarily involves avoidance of allergen-containing food, and more recently, therapies such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and the anti-IgE biologic omalizumab. However, these interventions are not curative. The gut microbiome has been implicated in the development and regulation of oral tolerance to food antigens. This narrative review explores the role of probiotics, fecal microbiota transplantation (FMT), dietary interventions, and the interaction between the microbiome and OIT as potential strategies to manage established FA. We also explore barriers to their proliferation as part of regular clinical care. We conclude that future research should (1) address how the microbiome interacts with immunotherapies other than OIT, (2) explore the role of novel microbiome-based treatments like FMT as potential adjuvants to existing food allergy therapeutics, and (3) focus on developing standardized protocols and endpoints for microbiome-based therapeutics. Full article

Background: Pistachio allergy is an increasingly recognized form of tree nut allergy and is strongly associated with cashew allergy due to pronounced molecular cross-reactivity. Despite its relatively low prevalence in the general population, pistachio allergy may result in severe systemic reactions and represents a significant diagnostic challenge, particularly in polysensitized patients. Objective: This narrative review aims to critically evaluate current diagnostic approaches to pistachio allergy, with a focus on molecular allergen components, mechanisms of cross-reactivity, clinical phenotypes, and the added value of advanced diagnostic tools for risk stratification. Methods: A narrative synthesis of the literature was conducted, integrating data from population-based studies, clinical cohorts, component-resolved diagnostics, basophil activation testing, and oral food challenge studies. Emphasis was placed on the diagnostic performance and clinical utility of extract-based versus molecular and functional assays. Results: Pistachio allergy is predominantly associated with sensitization to seed storage proteins, including 2S albumins, 7S vicilins, and 11S legumins, which share high sequence and structural homology with corresponding cashew allergens. This molecular relationship underlies frequent co-sensitization and clinical co-reactivity. Conventional extract-based tests show limited specificity, whereas component-resolved diagnostics and functional assays improve diagnostic precision, facilitate phenotype-based risk stratification, and may reduce the need for oral food challenges in selected patients. Conclusions: Accurate diagnosis of pistachio allergy requires an integrated approach combining clinical history with molecular and functional diagnostics. Incorporation of component-resolved diagnostics and basophil activation testing into diagnostic algorithms allows improved differentiation between asymptomatic sensitization and clinically relevant allergy, supporting individualized patient management and safer clinical decision-making. Full article

The protein kinase N family belongs to the AGC kinase group and contains three isozymes: PKN1, PKN2, and PKN3. Catalytic domains of PKNs share high sequence similarity, yet the proteins differ in tissue distribution, functions, and involvement in pathological processes. In particular, PKN3 has been implicated in tumor growth and metastatic progression, highlighting the need for isozyme-selective inhibitors as both research tools and therapeutic leads. Here, we report the rational design of selective PKN3 inhibitors based on distinctive structural features of this kinase. Two strategies were applied. First, the smaller threonine gatekeeper residue unique to PKN3 within the AGC group was exploited by derivatization of N-(2-aminoethyl)isoquinoline-5-sulfonamide (H-9) at position C8. Among the resulting compounds, a phenylamino-substituted derivative displayed the highest affinity, with a dissociation constant (K_D) of 23 nM and more than 1000-fold selectivity over protein kinase A. Second, bisubstrate-analog design was employed to enhance binding to basophilic AGC kinases through covalent attachment of a (d-Arg)₃-containing chain to H-9 derivatives. This approach yielded ARC-2603, which bound PKN3 with a K_D value of 0.2 nM and showed 5500-fold selectivity over PKAcα. The selectivity of ARC-2603 was further evaluated in a commercial panel of 397 protein kinases, which supported its utility as a highly selective PKN3 inhibitor. Full article

Diagnosing wheat allergy remains challenging due to the use of oral wheat provocations, which implicate risks to patients and highlights the need for safer, non-invasive diagnostic methods. Here, we present the first direct comparison of a pediatric and adult cohort to study wheat allergy and wheat tolerance using an improved and validated basophil activation test (BAT). Blood samples from 24 children and 26 adults, clinically classified as facing oral food challenges, were analyzed using our bin-based BAT, enabling standardized data analysis and visualization. In children, the BAT showed significantly higher median basophil activation in wheat-allergic compared to wheat-tolerant individuals. Receiver operating characteristic analysis revealed that BAT responses to wheat, gluten, and gliadin extracts (area under the curve (AUC): 0.71–0.73) had greater diagnostic accuracies than extract-based wheat and gluten-specific immunoglobulin E (sIgE) measurements (AUC: 0.69, 0.70). However, Tri a 19-sIgE, showed the highest diagnostic performance (AUC: 0.97). In adults, BAT responses did not differ significantly between allergic and tolerant individuals. The bin-based BAT is a robust and reproducible diagnostic tool for wheat allergy diagnosis with automated data analysis capabilities. Significant differences were only evident in the pediatric cohort, indicating age-related immunological differences in basophil responsiveness or immune sensitization profiles. These differences could be linked to immune system maturation, variations in immunoglobulin E (IgE) avidity, or differential expression of the high-affinity IgE receptor (FcεRI) on basophils. While Tri a 19 sIgE was the best single predictor in children, its clinical utility remains controversial due to conflicting results in the scientific literature. Full article

Determining hematological values is essential to provide baseline health and condition data. We evaluated the hematological parameters of free-living individuals of Caiman crocodilus and Melanosuchus niger from the middle Negro River region of Brazil. We captured 18 C. crocodilus and 16 M. niger. Blood was drawn using syringes containing 10% EDTA, and blood parameters were determined as previously described. The analyzed erythrocyte parameters were similar across the species, demonstrating that, despite their different sizes, they share similar strategies for oxygen absorption and transport in the blood. In the morphological analysis of blood cells, erythrocytes, erythroblasts, thrombocytes, lymphocytes, neutrophils, azurophils, heterophils, and basophils were found, and, in the quantification of leukocytes and thrombocytes, it was noted that lymphocytes are the central cells in the blood of the Amazonian caiman. In the plasma metabolite results, no significant differences were observed between glucose and total protein levels. Key physiological parameters were established to assess the health of C. crocodilus and M. niger, enabling the application of this information to sustainable captive production programs and helping to reduce pressure on wild populations. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype associated with a poor prognosis and limited treatment options. Inflammatory and hematological biomarkers have emerged as potential tools for disease characterization, particularly in low-resource settings. Methods: This cross-sectional analytical study was conducted between July 2022 and February 2024 at Dalal Jamm Hospital in Dakar, Senegal, and included 120 women: 40 with TNBC, 40 with hormone-dependent breast cancer (HDBC), and 40 healthy controls. Blood samples were collected at diagnosis before any treatment to measure complete blood counts and C-reactive protein (CRP) levels. Inflammatory ratios—neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR)—were calculated. Results: TNBC patients displayed a distinct inflammatory profile characterized by elevated neutrophil counts, CRP, NLR, and MLR, as well as reduced lymphocyte and basophil percentages compared to healthy controls. NLR > 1.12 demonstrated strong discriminatory ability (AUC = 0.847; sensitivity 90%; specificity 65%). Differences between TNBC and HDBC were less pronounced, except for CRP and basophil levels. Multivariate analysis confirmed independent associations of elevated NLR, CRP, and neutrophils with TNBC. Conclusions: These findings provide new insights into the inflammatory and hematological characteristics of TNBC in this population and support further investigation of accessible biomarkers for early disease stratification in similar settings. Full article

This study presents the first documented case of a disease syndrome in cultured largefin longbarbel catfish (Hemibagrus macropterus). The condition is characterized by massive abdominal pseudotumor formation, severe cachexia, and functional gonadal arrest. Comprehensive pathological investigation revealed that the pseudotumor was encapsulated by fibroblasts and primarily composed of host-derived, poorly differentiated hyperplastic cells, interspersed with invasive, basophilic Type III cells. These cells and associated inflammatory–fibrotic lesions were also disseminated in the gill, kidney and spleen. Systematic diagnostic approaches, including microbiology and transmission electron microscopy, found no evidence of conventional bacterial or viral pathogens. Metagenomic analysis further supported these findings and suggested a link to infection by an as-yet-unidentified eukaryotic parasite, with Microsporidia or Ichthyosporea being the primary candidates. Functional (KEGG) profiling of the pseudotumor tissue further revealed a molecular signature consistent with active cellular proliferation and metabolism. We propose that the pseudotumor acts as a metabolically active “nutrient sink,” driving the systemic catabolism that underlies the severe cachexia and reproductive arrest. This work provides the first case of a eukaryotic parasite-induced pseudotumorous syndrome in fish, which represents an emerging threat to conservation aquaculture and offering novel insights into parasite-mediated host metabolic hijacking and tumor-mimicry. Full article