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17 pages, 3933 KB  
Article
Immunodominant IgM Epitopes of the Angiostrongylus cantonensis Galectin-1 and Galectin-2 Proteins Recognized by Patients’ Sera: Optimization of an ELISA Assay for Human Acute Diagnosis of Angiostrongyliasis
by Paloma Napoleão-Pêgo, Guilherme C. Lechuga, João P. R. S. Carvalho, Flávio R. da Silva, Karyne Rangel, Mariana S. Freita, Jessica A. Waterman, Arnaldo Mandonado-Junior, Carlos Graeff-Teixeira and Salvatore G. De-Simone
Int. J. Mol. Sci. 2026, 27(12), 5381; https://doi.org/10.3390/ijms27125381 - 15 Jun 2026
Viewed by 117
Abstract
Angiostrongyliasis, the primary cause of eosinophilic meningitis, represents an emerging disease caused by Angiostrongylus cantonensis larvae, inadvertently transmitted to humans. The diagnosis of human angiostrongyliasis relies on epidemiological features, clinical symptoms, medical history, and laboratory findings, notably hyper eosinophilia in blood and cerebrospinal [...] Read more.
Angiostrongyliasis, the primary cause of eosinophilic meningitis, represents an emerging disease caused by Angiostrongylus cantonensis larvae, inadvertently transmitted to humans. The diagnosis of human angiostrongyliasis relies on epidemiological features, clinical symptoms, medical history, and laboratory findings, notably hyper eosinophilia in blood and cerebrospinal fluid. Consequently, accurate diagnosis is challenging and prone to confusion with other parasitic diseases. The quest for an early, rapid, and specific diagnostic test for angiostrongyliasis persists, driven by the imperative for enhanced test specificity. This study focused on mapping IgM epitopes on galectin-1 (Gal-1) and galectin-2 (Gal-2) proteins derived from A. cantonensis. The specificity of the epitopes was assessed using database homology analysis. After selecting specific epitopes, researchers chemically synthesized 12 individual multi-antigen peptides (MAPs4) and one chimeric polypeptide that is 65 amino acids long. The effectiveness of these synthesized peptides was subsequently evaluated using enzyme-linked immunoassay (ELISA). A total of twelve unique IgM epitopes were discovered; five were linked to Gal-1, while seven were linked to Gal-2. An ELISA-peptide method confirmed the twelve epitopes, and then the chimeric polypeptide was employed as an antigen to coat ELISA plates. This setup was evaluated with patients’ sera to diagnose strongyloidiasis in vitro. This study provides a comprehensive representation of the IgM epitopes of Gal-1 and Gal-2 from A. cantonensis. ELISA data utilizing the chimeric polypeptide demonstrate that the selected sequences hold promise for the development of a specific immunological assay tailored for the acute diagnosis of angiostrongyliasis infections. Full article
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18 pages, 4080 KB  
Article
Prognostic Significance of Selected Tumor Stroma Parameters in Patients with HER2-Positive Breast Cancer Treated with Adjuvant Trastuzumab
by Aleksandra Ambicka, Aleksandra Grela-Wojewoda, Joanna Niemiec, Katarzyna Mularz, Agnieszka Harazin-Lechowska, Janusz Ryś and Agnieszka Adamczyk
Cancers 2026, 18(8), 1243; https://doi.org/10.3390/cancers18081243 - 14 Apr 2026
Viewed by 622
Abstract
Background: While the prognostic and predictive value of tumor cell–derived features such as grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and Ki67 index is well established in breast cancer, less is known about the prognostic [...] Read more.
Background: While the prognostic and predictive value of tumor cell–derived features such as grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and Ki67 index is well established in breast cancer, less is known about the prognostic role of tumor stroma. This study aimed to evaluate stromal parameters in HER2-positive breast cancer patients treated with adjuvant trastuzumab. Material and methods: The study included 224 patients (T ≥ 1, N ≥ 0, M0) who underwent radical treatment followed by adjuvant chemotherapy, hormone therapy (if ER/PR-positive), and trastuzumab. The following histological and immunohistochemical parameters were analyzed: stroma type, tumor-infiltrating lymphocytes (TILs), eosinophils, neutrophils, central area of fibrosis, necrosis, and programmed cell death protein ligand 1 (PD-L1) expression in tumor and stromal cells. Results: Low TILs percentage (≤50%) was associated with lower tumor grade (G2) (p = 0.013) and ER/PR positivity (p = 0.001). Tumors lacking PD-L1 expression had a lower percentage of TILs (p < 0.001), less frequently exhibited tumor-associated neutrophilia (p = 0.019), and more often presented with desmoplastic stroma (p < 0.001). The following parameters were associated with prognosis: TILs percentage, stroma type, and PD-L1 expression. High TILs percentage (>50%) was an independent positive prognostic factor. Conclusions: In patients with HER2-positive breast cancer treated with adjuvant trastuzumab, the percentage of TILs, stroma type, and PD-L1 expression are prognostically relevant. Specifically, a TILs percentage >50% independently predicts favorable outcomes. Routine evaluation of stromal features may provide additional prognostic information and support treatment planning. Full article
(This article belongs to the Section Tumor Microenvironment)
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21 pages, 1830 KB  
Review
Friend or Foe? Eosinophilic Granulomatosis with Polyangiitis (EGPA) Onset After Dupilumab: Report of Two Cases and a Narrative Review of the Literature
by Alessia Gatti, Giulia Fontana, Jacopo Mora, Franco Franceschini, Ilaria Cavazzana, Paola Toniati and Francesca Regola
Rheumato 2026, 6(2), 10; https://doi.org/10.3390/rheumato6020010 - 7 Apr 2026
Viewed by 886
Abstract
Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, [...] Read more.
Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications. Full article
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14 pages, 2510 KB  
Article
Effects of the Hypomethylating Agent Guadecitabine on Peripheral Blood Mononuclear Cell Methylomes and Immune Cell Populations in Small-Cell Lung Cancer Patients
by Elnaz Abbasi Farid, Shu Zhang, Zhen Fu, Collin M. Coon, Daniela Matei, Shadia I. Jalal and Kenneth P. Nephew
Pharmaceuticals 2026, 19(4), 542; https://doi.org/10.3390/ph19040542 - 28 Mar 2026
Viewed by 777
Abstract
Background/Objectives: Epigenetic modifications, particularly DNA methylation, contribute to tumor progression and therapy resistance. Guadecitabine, a hypomethylating agent (HMA), has shown promising clinical activity when combined with carboplatin in preclinical models. We evaluated the combination of guadecitabine with carboplatin as a second-line treatment for [...] Read more.
Background/Objectives: Epigenetic modifications, particularly DNA methylation, contribute to tumor progression and therapy resistance. Guadecitabine, a hypomethylating agent (HMA), has shown promising clinical activity when combined with carboplatin in preclinical models. We evaluated the combination of guadecitabine with carboplatin as a second-line treatment for extensive-stage small-cell lung cancer (SCLC; NCT03913455), one of the deadliest malignancies. Here, we report methylome changes in peripheral blood mononuclear cells (PBMCs) collected at baseline and during treatment from patients on the trial. Methods: PMBC DNA was analyzed using Infinium HumanMethylationEPIC v1.0 bead chips. Data were processed, and differentially methylated positions (DMPs) were identified and analyzed for pathway enrichment using bioinformatic approaches, and immune deconvolution analyses were conducted to investigate the impact on immune cell composition. Results: Direct comparison of PBMCs between cycle 2 day 5 (C2D5; post-treatment) vs. cycle 1 day 1 (C1D1; pre-treatment) revealed a greater number of hypomethylated DMPs (380 DMPs in C2D5 vs. C1D1 PBMCs; p < 0.05, |β| > 20%). Moreover, when first compared with normal PBMCs from cancer-free controls, the number of hypomethylated DMPs was even greater in C2D5 than in C1D1 (1771 vs. 237 DMPs, respectively; p < 0.05, |β| > 20%). Long interspersed nucleotide elements-1 (LINE-1) were significantly hypomethylated in PBMCs after HMA treatment (C2D5 vs. C1D1). Pathway analysis of hypomethylated DMPs revealed significant alterations in key signaling pathways, including NF-κB, Rho GTPase, and pulmonary fibrosis in C1D1 vs. C2D5. Normal PBMCs to C1D1 PBMCs revealed changes in IL-3 signaling, Fcγ receptor-mediated phagocytosis, and molecular mechanisms of cancer. Deconvolution analysis revealed a greater percentage of monocytes in C1D1 vs. normal PBMCs; after HMA treatment, percentages of monocytes and B cells decreased, while the eosinophil percentage increased in C1D1 vs. C2D5. Conclusions: HMA treatment has a global impact on PBMC methylomes in cancer patients. DNA methylation changes were associated with biological pathways related to PBMC function, and shifts in distinct immune cell populations were observed. Full article
(This article belongs to the Special Issue Targeting Epigenetic Regulation for Cancer Therapy)
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22 pages, 816 KB  
Review
Understanding Eosinophil Heterogeneity: The Known and Unknown
by Alexander Ruzic, Michael Trus, Roma Sehmi and Manali Mukherjee
Cells 2026, 15(6), 564; https://doi.org/10.3390/cells15060564 - 21 Mar 2026
Viewed by 1449
Abstract
Eosinophils are multifunctional granulocytes with central roles in the pathobiology of chronic airway diseases. While systemic eosinophilia (>300 cells/μL) is a well-established biomarker to guide therapeutic decision-making, accumulating evidence indicates that eosinophils are not a uniform population but instead exhibit substantial phenotypic and [...] Read more.
Eosinophils are multifunctional granulocytes with central roles in the pathobiology of chronic airway diseases. While systemic eosinophilia (>300 cells/μL) is a well-established biomarker to guide therapeutic decision-making, accumulating evidence indicates that eosinophils are not a uniform population but instead exhibit substantial phenotypic and functional heterogeneity across biological compartments, inflammatory states, and disease contexts. In this review, we synthesize the current understanding of eosinophil heterogeneity in airway diseases and critically evaluate the strengths and limitations of surface marker-based approaches, with emphasis on CD62L/L-selectin-defined subpopulations. Although CD62L-based stratification has provided valuable insight into eosinophil activation and tissue localization, its limited specificity, inconsistent clinical associations, and reliance on murine models restrict its utility as a framework for eosinophil subtyping in humans. We highlight how transcriptomic and proteomic profiling has transformed the field by revealing that peripheral blood eosinophils are largely quiescent, whereas disease-relevant functional specialization is predominantly acquired within inflamed tissues in response to cues from the local microenvironment. These molecular studies support a model in which eosinophil heterogeneity represents a continuum of activation rather than discrete, fixed subsets. A refined, integrative approach to understanding eosinophil heterogeneity is critical for improving patient stratification, predicting therapeutic responsiveness, and optimizing precision medicine strategies in chronic airway diseases. Full article
(This article belongs to the Special Issue Eosinophils and Their Role in Allergy and Related Diseases)
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20 pages, 994 KB  
Review
Chronic Rhinosinusitis with Nasal Polyps: A “Module-First” Review of Murine Models and Chemical Interventions
by Yunfei Gao, Gengluan Liu, Caiyan An, Hesen Huang, Huaixiang Zhou, Junjing Zhang, Yunping Fan and Ningning Li
Molecules 2026, 31(5), 781; https://doi.org/10.3390/molecules31050781 - 26 Feb 2026
Viewed by 1136
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) comprises multiple molecular endotypes that only partly align with the clinical phenotype, which complicates target selection and interpretation of treatment effects. Human omics and biomarker studies define candidate pathways, but causal attribution of specific nodes to lesion [...] Read more.
Chronic rhinosinusitis with nasal polyps (CRSwNP) comprises multiple molecular endotypes that only partly align with the clinical phenotype, which complicates target selection and interpretation of treatment effects. Human omics and biomarker studies define candidate pathways, but causal attribution of specific nodes to lesion formation and remodeling requires perturbable in vivo systems. Here, we present a “module-first” framework that links murine induction paradigms to epithelial–immune–stromal circuits and to a minimal, module-matched endpoint set for reproducible causal inference. We summarize commonly used CRSwNP-like protocols (allergen/protease ± SEB, aeroallergen + SEB, innate trigger-enriched paradigms, and modifier layers), emphasize operational pathology terminology (“polyp-like lesion” versus “true polyp”), and propose a uniform causal template for validated pathway modules (alarmins/IL-33–NF-κB, type 2/ILC2–eosinophil, IL-17A/neutrophil, Wnt/EMT remodeling, and JAK/STAT kinase convergence). Finally, we organize chemical and molecular interventions by leverage point and propose an ARRIVE-aligned Minimum Reporting Set to standardize model anchoring, target engagement, and cross-study comparability. This module-first roadmap is intended to accelerate mechanism-linked discovery and preclinical validation of tractable drug targets in CRSwNP. Importantly, this module-first roadmap is intended as a heuristic organizing principle rather than an exhaustive taxonomy, because pathway modules can overlap and shift dynamically across time and tissue compartments in vivo. Full article
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27 pages, 2418 KB  
Review
Prebiotics and Synbiotics in Asthma: An Integrative Review of Human Trials and Murine Meta-Analysis
by Louise C. Bonnard, Graham R. Sharpe, Matthew Martin, Georgina F. Dodd and Neil C. Williams
Nutrients 2026, 18(4), 683; https://doi.org/10.3390/nu18040683 - 20 Feb 2026
Cited by 1 | Viewed by 820
Abstract
Background/Objectives: The objectives of this study were to systematically review the literature on the effects of prebiotics and synbiotics on asthma control, lung function and asthma-associated inflammation from murine and human trials. Methods: A systematic review was performed following the PRISMA guidelines across [...] Read more.
Background/Objectives: The objectives of this study were to systematically review the literature on the effects of prebiotics and synbiotics on asthma control, lung function and asthma-associated inflammation from murine and human trials. Methods: A systematic review was performed following the PRISMA guidelines across multiple databases. A meta-analysis was performed on murine trials assessing asthma-associated inflammation and airway hyperresponsiveness, whilst a narrative review of human studies assessed asthma control, lung function, and inflammation. Results: Seventeen studies met the eligibility criteria for inclusion; eleven murine studies were included for meta-analysis and six human studies were for narrative review. The meta-analysis revealed significant effects of prebiotics and synbiotics on multiple markers of asthma-associated inflammation. Prebiotic intervention significantly reduced airway hyperresponsiveness (AHR) and type 2 cytokines (IL-4, IL-5, IL-13) and various cell counts, including neutrophil, macrophage, lymphocyte, eosinophil, and total bronchoalveolar (BALF). Synbiotics were also effective in reducing type 2 cytokines, including, IL-4, IL-5, IL-13, and lymphocytes, eosinophils, and total BALF cell count. A narrative review of human intervention trials of prebiotics and/or synbiotics revealed improvements in lung function, asthma control, and systemic and airway inflammation. Conclusions: This review indicates that dietary prebiotics and synbiotics may be suitable adjunct treatments to support asthma management, but further well-controlled human RCTs are required. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
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15 pages, 2514 KB  
Article
Dupilumab-Related Hypereosinophilia in Patients Treated for Type 2 Diseases: Evidence from a 24-Month Prospective Real-Life Study
by Ilaria Mormile, Daniele La Prova, Paolo Pezzella, Giuliano Di Caprio, Amato de Paulis, Elena Cantone and Aikaterini Detoraki
J. Clin. Med. 2026, 15(4), 1525; https://doi.org/10.3390/jcm15041525 - 14 Feb 2026
Viewed by 1071
Abstract
Background/Objectives: Dupilumab is a human monoclonal antibody that targets both IL-4 and IL-13 signaling. Eosinophilia has been reported as a potential adverse event in treated patients in randomized controlled trials and 12-month real-life studies. This real-life, 24-month prospective study investigated the prevalence of [...] Read more.
Background/Objectives: Dupilumab is a human monoclonal antibody that targets both IL-4 and IL-13 signaling. Eosinophilia has been reported as a potential adverse event in treated patients in randomized controlled trials and 12-month real-life studies. This real-life, 24-month prospective study investigated the prevalence of eosinophilia, its consequences, and the effectiveness of dupilumab in a cohort of patients with severe asthma, chronic rhinosinusitis with nasal polyps, and atopic dermatitis. Methods: A total of 66 adult patients treated with dupilumab were included in this study. ACT, SNOT-22, and Smell-VAS, EASI, and absolute blood eosinophil count (AEC) were assessed according to the type of diagnosis at baseline (T0), after 6 (T6), 12 (T12), 18 (T18), and 24 (T24) months post-dupilumab initiation. Results: All patients experienced significant improvement in both symptoms and disease control following dupilumab treatment. A total of 27 out of 66 (40.9%) patients developed eosinophilia within six months of treatment (AEC T6 mean ± SD 0.67 ± 0.68 109/L). Eosinophilia was generally mild and lasted on average for six months (AEC T12 mean ± SD 0.66 ± 0.65 109/L) with AEC normalization after 18 months of treatment (AEC T18 mean ± SD 0.58 ± 0.48 109/L). Ten patients (15.15%) developed hypereosinophilia, but no symptoms or signs of eosinophilic-related organ damage have been observed, with no need for dupilumab discontinuation. Conclusions: Dupilumab-related eosinophilia was common, generally mild, and transient, whereas persistent hypereosinophilia occurred in a small group of patients in the absence of symptoms or signs of eosinophilic damage. Full article
(This article belongs to the Section Immunology & Rheumatology)
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28 pages, 7890 KB  
Article
Ectoparasite- and Vector-Borne-Related Dermatoses: A Single-Centre Study with Practical Diagnostic and Management Insights in a One Health Perspective
by Giovanni Paolino, Barbara Moroni, Antonio Podo Brunetti, Anna Cerullo, Carlo Mattozzi, Giovanni Gaiera, Manuela Cirami, Dino Zilio, Mario Valenti, Andrea Carugno, Giuseppe Esposito, Nicola Zerbinati, Carmen Cantisani, Franco Rongioletti, Santo Raffaele Mercuri and Matteo Riccardo Di Nicola
J. Clin. Med. 2026, 15(2), 851; https://doi.org/10.3390/jcm15020851 - 20 Jan 2026
Viewed by 1173
Abstract
Background: Parasitic skin-related conditions represent a frequent and evolving challenge in human dermatology, as they often mimic other dermatoses, and are increasingly complicated by therapeutic resistance. With this study, we aimed to provide a practical, clinician-oriented overview of our experience, contextualising it [...] Read more.
Background: Parasitic skin-related conditions represent a frequent and evolving challenge in human dermatology, as they often mimic other dermatoses, and are increasingly complicated by therapeutic resistance. With this study, we aimed to provide a practical, clinician-oriented overview of our experience, contextualising it within the current literature. Materials and Methods: We conducted a retrospective, single-centre observational study, reporting a case series of 88 patients diagnosed with parasitic or arthropod-related skin infestations at the San Raffaele Hospital Dermatology Unit (Milan) between 2019 and 2024, and integrated a concise narrative review of contemporary evidence on diagnosis, non-invasive imaging and management. For each case, we documented clinical presentation, dermoscopic or reflectance confocal microscopy (RCM) findings, and treatment response. Non-invasive tools (dermoscopy, videodermoscopy, RCM) were used when appropriate. Results: The spectrum of conditions included flea bites, bed bug bites, cutaneous larva migrans, subcutaneous dirofilariasis, Dermanyssus gallinae dermatitis, pediculosis, tick bites (including Lyme disease), myiasis, scabies, and cutaneous leishmaniasis. One case of eosinophilic dermatosis of haematologic malignancy was also considered due to its possible association with arthropod bites. Non-invasive imaging was critical in confirming suspected infestations, particularly in ambiguous cases or when invasive testing was not feasible. Several cases highlighted suspected therapeutic resistance: a paediatric pediculosis and three adult scabies cases required systemic therapy after standard regimens failed, raising concerns over putative resistance to permethrin and pyrethroids. In dirofilariasis, the persistence of filarial elements visualised by RCM justified the extension of antiparasitic therapy despite prior surgical removal. Conclusions: Our findings underline that accurate diagnosis, early intervention, and tailored treatment remain essential for the effective management of cutaneous infestations. The observed vast spectrum of isolated parasites reflects broader health and ecological dynamics, including zoonotic transmission, international mobility, and changing environmental conditions. At the same time, diagnostic delays, inappropriate treatments, and neglected parasitic diseases continue to pose significant risks. To address these challenges, clinicians should remain alert to atypical presentations, and consider a multidisciplinary approach including the consultation with parasitologists and veterinarians, as well as the incorporation of high-resolution imaging and alternative therapeutic strategies into their routine practice. Full article
(This article belongs to the Section Dermatology)
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12 pages, 649 KB  
Article
Short-Term Effects of Dupilumab in Eosinophilic COPD
by Chiara Lupia, Daniela Pastore, Giuseppina Marrazzo, Giada Procopio, Antonio Giacalone, Federica Marrelli, Mariarosanna De Fina, Adele Emanuela De Francesco, Alessandro Vatrella, Santi Nolasco, Raffaele Campisi, Nunzio Crimi, Claudia Crimi, Girolamo Pelaia and Corrado Pelaia
J. Clin. Med. 2026, 15(2), 775; https://doi.org/10.3390/jcm15020775 - 18 Jan 2026
Cited by 2 | Viewed by 1041
Abstract
Background/Objectives: Patients with eosinophilic chronic obstructive pulmonary disease (COPD) often remain symptomatic despite optimized triple inhaled therapy. Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit, thereby inhibiting IL-4 and IL-13 signaling. Evidence from randomized trials supports dupilumab [...] Read more.
Background/Objectives: Patients with eosinophilic chronic obstructive pulmonary disease (COPD) often remain symptomatic despite optimized triple inhaled therapy. Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit, thereby inhibiting IL-4 and IL-13 signaling. Evidence from randomized trials supports dupilumab for add-on treatment of type 2-high COPD, but data referring to short-term effectiveness in clinical practice are quite limited. Methods: We conducted an observational, compassionate-use study enrolling 13 consecutive outpatients with eosinophilic COPD (blood eosinophils ≥ 300 cells/µL) receiving add-on biologic therapy with dupilumab 300 mg every two weeks. Clinical (CAT, mMRC), functional (spirometry and body plethysmography), and inflammatory parameters (blood eosinophils/basophils, fibrinogen, FeNO) were evaluated at baseline and after four weeks of treatment. Safety was monitored after injection in a clinical setting, as well as via weekly phone follow-up. Results: Participants (84.6% male; mean age 67.08 ± 11.42 years) experienced rapid and clinically meaningful improvements at four weeks. CAT score decreased from baseline 21.40 ± 6.22 to 14.00 ± 5.58 (p < 0.001) and mMRC scale from 2.90 ± 0.73 to 1.80 ± 0.63 (p < 0.0001), respectively. Pre-bronchodilator FEV1 increased from baseline 1.35 ± 0.65 L to 1.59 ± 0.84 L (p < 0.05), and FVC from 2.36 ± 0.92 L to 2.83 ± 1.11 L (p < 0.01). A marked lung deflation was observed: indeed, residual volume declined from baseline 4.17 ± 1.98 L to 3.47 ± 2.07 L (p < 0.05), with a concomitant reduction in specific effective airway resistance (from baseline 3.15 ± 1.77 to 2.43 ± 1.44 kPa·s; p < 0.05) associated with significant increases in mid-expiratory flow (FEF25−75: from baseline 0.62 ± 0.38 to 0.86 ± 0.71 L/s; p < 0.05) and peak expiratory flow (3.80 ± 1.40 to 4.48 ± 1.79 L/s; p < 0.01). Type 2 inflammatory biomarkers changed as follows: blood eosinophil count fell from baseline 390.0 ± 43.75 to 190.0 ± 65.47 cells/µL (p < 0.001); blood basophil number decreased from baseline 37.50 ± 13.89 to 26.25 ± 13.02 cells/µL (p < 0.001); plasma fibrinogen lowered from baseline 388.4 ± 54.81 to 334.9 ± 72.36 mg/dL (p < 0.01); FeNO levels dropped from baseline 23.95 ± 18.10 to 14.00 ± 2.04 ppb (p < 0.0001). Dupilumab was well tolerated, and no treatment-related serious adverse events or discontinuations were detected. Conclusions: Within an exploratory context of daily medical activity referring to eosinophilic COPD already treated with maximal inhaled therapy, we found relevant therapeutic effects of a four-week add-on treatment with dupilumab. In particular, our patients manifested rapid improvements in symptoms, airflow limitation, and lung hyperinflation, paralleled by significant decrements of type 2 inflammatory signatures. Such encouraging results were associated with a favorable short-term safety profile. However, larger and longer studies are necessary to corroborate these preliminary findings. Full article
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23 pages, 5773 KB  
Article
Mutational Landscape Analysis of BRCA1/2 and Identification of Extracellular-Vesicle-Related Biomarkers in Triple-Negative Breast Cancer
by Yuqiu Hu, Jiali Wu, Lu Sun, Zishan Xie, Ming Li, Lu Yuan, Rui Huang and Weixing Zhang
Biomedicines 2026, 14(1), 178; https://doi.org/10.3390/biomedicines14010178 - 14 Jan 2026
Viewed by 902
Abstract
Background: Triple-negative breast cancer (TNBC), defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is associated with increased BRCA1/2 mutation rates. Extracellular vesicles (EVs) play a pivotal role in TNBC progression. [...] Read more.
Background: Triple-negative breast cancer (TNBC), defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is associated with increased BRCA1/2 mutation rates. Extracellular vesicles (EVs) play a pivotal role in TNBC progression. This study aimed to analyze BRCA1/2 mutations and identify EV-related biomarkers for TNBC by employing TNBC-related datasets and EV-related genes (EVRGs). Methods: Initially, BRCA1/2 mutations in TNBC patients were examined. Differentially expressed EVRGs (DE-EVRGs) were identified by integrating the results of both differential expression analysis and weighted gene co-expression network analysis (WGCNA). Biomarkers were identified using Receiver Operating Characteristic (ROC) and Kaplan–Meier (K–M) analyses. Finally, functional enrichment, drug prediction, molecular docking, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses were performed. Results: Waterfall plots indicated that TP53 exhibited the highest mutation frequency in both the mutation (MUT) and wild-type (WT) group. Four distinct types of immune cells (for example, eosinophils and neutrophils) showed significantly elevated expression levels in the WT group. Notably, PLA2G5 was identified as a biomarker of TNBC and its expression was significantly lower in TNBC (p = 0.0025). Functional analysis demonstrated that PLA2G5 is enriched in the “drug metabolism cytochrome P450” pathway. Finally, 20 drugs targeting PLA2G5 were identified, among which leukotriene C4 demonstrated a binding affinity of −7.2 kcal/mol. This finding suggests that leukotriene C4 has potential therapeutic applications for the treatment of TNBC. Conclusions: Our study found significant differences between the MUT and WT groups, identifying PLA2G5 as a biomarker for TNBC and offering a theoretical basis for TNBC treatment. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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8 pages, 9115 KB  
Case Report
Basal Cell Carcinoma of the Cloacal Aperture in a Red Kangaroo (Osphranter rufus)
by Louise van der Weyden, Agustina Fitte and Nicolize O’Dell
Vet. Sci. 2025, 12(12), 1145; https://doi.org/10.3390/vetsci12121145 - 1 Dec 2025
Viewed by 854
Abstract
There have been few reports of neoplasia in kangaroos to date. In this report, we describe a 13-year-old male captive Red kangaroo (Osphranter rufus) that developed a mass on the right side of the cloacal aperture. Histopathological analysis of a biopsy [...] Read more.
There have been few reports of neoplasia in kangaroos to date. In this report, we describe a 13-year-old male captive Red kangaroo (Osphranter rufus) that developed a mass on the right side of the cloacal aperture. Histopathological analysis of a biopsy of the mass revealed proliferating, neoplastic epithelial islands with necrotic centres infiltrating a moderately desmoplastic dermis. The islands were generally large with extensive central caseation necrosis consisting of cellular debris and innumerable neutrophils. The neoplastic epithelial cells resembled the basal cells observed in the basal layer of the epidermis and were characterised by scant to moderate eosinophilic cytoplasm with indistinct cytoplasmic margins. The diagnosis was basal cell carcinoma (BCC). This is the first report of a BCC in a kangaroo, and we compare the findings with that seen in dogs, cats and humans. Full article
(This article belongs to the Section Anatomy, Histology and Pathology)
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8 pages, 3914 KB  
Case Report
A Humanized Anti-IL-4Rα Monoclonal Antibody Improves Aural Fullness
by Yiyun Zhang, Mengwen Shi, Yan Zhou, Jianjun Chen, Huabin Li and Yu Sun
J. Otorhinolaryngol. Hear. Balance Med. 2025, 6(2), 21; https://doi.org/10.3390/ohbm6020021 - 21 Nov 2025
Viewed by 1255
Abstract
Background and Clinical Significance: Otitis media with effusion (OME) is characterized by persistent middle ear effusion without acute infection. Type 2 inflammation, mediated by IL-4 and IL-13 signaling via the IL-4Rα receptor, has been implicated in the pathogenesis of chronic rhinosinusitis with [...] Read more.
Background and Clinical Significance: Otitis media with effusion (OME) is characterized by persistent middle ear effusion without acute infection. Type 2 inflammation, mediated by IL-4 and IL-13 signaling via the IL-4Rα receptor, has been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and possibly OME. Refractory OME in adults remains a therapeutic challenge, as conventional treatments often fail to achieve long-term resolution. Targeted biologic therapies that modulate type 2 inflammation may offer a novel treatment option. Case Presentation: We report the case of a 60-year-old man with a 15-year history of allergic rhinitis and CRSwNP, complicated by recurrent asthma exacerbations, who presented with bilateral aural fullness, hearing loss, and tinnitus. His symptoms persisted despite repeated tympanic punctures, Eustachian tube insufflation, and corticosteroid therapy. Otoscopy revealed dull tympanic membranes with effusion, and audiometry showed conductive hearing loss with a B-type tympanogram on the left. Laboratory findings demonstrated mild peripheral eosinophilia. The patient was diagnosed with OME, likely secondary to type 2 inflammation. After nine biweekly injections of Stapokibart (CM310)—a humanized monoclonal antibody targeting IL-4Rα—aural fullness completely resolved. Otoscopic findings and tympanograms normalized, and hearing thresholds improved significantly. Retrospective evaluation using Iino’s diagnostic framework suggested that the patient did not meet the full criteria for eosinophilic otitis media (EOM); nevertheless, marked symptomatic and functional improvement was achieved. No recurrence or adverse effects were observed during follow-up. Conclusions: This case suggests that IL-4Rα blockade with Stapokibart may be effective in treating refractory OME associated with type 2 inflammation, even in patients who do not fulfill the diagnostic criteria for EOM. These findings highlight the potential of anti-IL-4Rα biologics as a novel therapeutic option for middle ear diseases driven by type 2 inflammation. Full article
(This article belongs to the Special Issue Etiology, Diagnosis, and Treatment of Congenital Hearing Loss)
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22 pages, 2503 KB  
Article
Der p 23, A Frequent IgE Sensitizer in Humans, Induces Airway Inflammation in Mice
by Karen Donado, Luis Durango, Inés Benedetti, Nikolina Todorovic, Ronald Regino, Ana Lozano, Victoria Marrugo, Randy Reina, Dilia Mercado, Nathalie Acevedo, Josefina Zakzuk, Enrique Fernández-Caldas, Walter Keller, Leonardo Puerta and Luis Caraballo
Int. J. Mol. Sci. 2025, 26(21), 10765; https://doi.org/10.3390/ijms262110765 - 5 Nov 2025
Cited by 2 | Viewed by 4301
Abstract
Der p 23 induces a high-frequency sensitization in allergic individuals. However, its allergenic activity and clinical impact are scarce. We aimed to evaluate the ability of rDer p 23 to induce allergic inflammation in a mouse model and to test IgE reactivity in [...] Read more.
Der p 23 induces a high-frequency sensitization in allergic individuals. However, its allergenic activity and clinical impact are scarce. We aimed to evaluate the ability of rDer p 23 to induce allergic inflammation in a mouse model and to test IgE reactivity in humans. Female Balb/c mice were sensitized and challenged with rDer p 23 and Dermatophagoides pteronyssinus extract. Specific antibodies were determined by ELISA, inflammatory cell infiltration and goblet cells hyperplasia were evaluated by lung histology, and bronchial hyperreactivity (BHR) was assessed by the FinePoint RC SystemTM and whole-body plethysmography (WBP). IgE reactivity was evaluated by ELISA, the basophils activation test (BAT) and the skin pick test (SPT) in humans. rDer p 23, produced in Escherichia coli, adopts a random coil structure, predominantly exists in a monomeric state, and exhibits high stability. rDer p 23-treated mice showed a significant increase in lung resistance and bronchial hyperreactivity, as well as in eosinophils, neutrophils, and T cell count in bronchoalveolar lavage fluid (BALF). Cytokine and antibodies profiles were biased to a Type-2 response. No significant difference was observed in group 2 Innate Lymphoid Cells (ILC-2s) in lung and regulatory T cells (Treg) in the spleen. In asthmatic individuals sensitized to D. pteronyssinus, serum IgE reactivity to rDer p 23 was 67.5%. BAT and SPT results were significantly higher in allergic patients. Our findings support the pro-allergenic role of rDer p 23 in the development of the pathological features of asthma. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Allergy and Asthma: 3rd Edition)
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19 pages, 7813 KB  
Article
Immunogenicity and Integration of a Decellularized Extracellular Matrix-Based Scaffold for the Reconstruction of Human Foreskin: A Preclinical Animal Study
by Luca Pennasilico, Margherita Galosi, Lucia Biagini, Valentina Riccio, Caterina Di Bella, Federica Serino, Sara Sassaroli, Felice Ciabocco, Elena Bondioli, Giacomo Rossi, Vincenzo Aiello, Andrea Pratesi and Angela Palumbo Piccionello
Bioengineering 2025, 12(11), 1186; https://doi.org/10.3390/bioengineering12111186 - 31 Oct 2025
Cited by 2 | Viewed by 5427
Abstract
The reconstruction of the foreskin using autografts is a complex procedure. A novel decellularisation method for epithelial tissue has been developed, producing an extracellular matrix scaffold from human donor foreskin. This study evaluated the immune response and integration of this scaffold after implantation [...] Read more.
The reconstruction of the foreskin using autografts is a complex procedure. A novel decellularisation method for epithelial tissue has been developed, producing an extracellular matrix scaffold from human donor foreskin. This study evaluated the immune response and integration of this scaffold after implantation in rats, focusing on inflammatory infiltrate, neovascularization, recellularization, and foreign body reaction. Twenty-six rats underwent a 1 cm infrascapular incision with scaffold implantation in the hypodermal layer. Group A (13 rats) was subject to a 30-day follow-up period, while Group B (13 rats) was subject to a 5-day follow-up period. Inflammation at the implantation site was scored from 0 (none) to 3 (severe). Tissue explants were. After 5 days (Group B) and 30 days (Group A), a tissue explant was performed and examined histologically and immunohistochemically. The clinical evaluation revealed slight signs of inflammation during the initial five days following the implantation procedure. Neutrophil (0.87 ± 0.35; 1 ± 0.53) and eosinophil (0.61 ± 0.51; 0.75 ± 0.46) presence was slight, with no significant differences between groups. Lymphocyte infiltration was moderate (1.87 ± 0.35; 1.75 ± 0.46), exceeding macrophage presence (1.25 ± 0.46; 1.12 ± 0.35). Neovascularization and cellular colonization were significantly greater at 30 days (2 ± 0.53; 2.42 ± 0.53) compared to 5 days (0.57 ± 0.21; 0.62 ± 0.32). Encapsulation remained mild in all cases, with no intergroup differences (0.87 ± 0.35). These findings indicate that the decellularized extracellular matrix derived from human foreskin elicits minimal immune response while promoting neovascularization and cellular repopulation. This supports its potential use as a biocompatible scaffold in reconstructive procedures. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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