Search Results (18)

Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by immune dysregulation and epidermal barrier dysfunction, in which eosinophils act as key effector cells contributing to tissue damage and persistent inflammation. This comprehensive review elucidates the multifaceted contributions of eosinophils to the progression of AD. Driven by key type 2 cytokines (notably IL-4, IL-5, and IL-13) and specific chemokines, eosinophils infiltrate lesional skin and undergo IgE-mediated degranulation. The subsequent release of cytotoxic granule proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase (EPX), directly induces keratinocyte apoptosis, exacerbates tissue remodeling, and sustains the local inflammatory cascade. Furthermore, we explore the intricate crosstalk between eosinophils and sensory neurons, which, alongside cytokines like IL-31, profoundly aggravates chronic pruritus. Consequently, modulating eosinophil activation and recruitment has emerged as a vital therapeutic approach. We systematically evaluate current and emerging pharmacological interventions, ranging from conventional topical corticosteroids to advanced targeted therapies. Particular emphasis is placed on the mechanistic impact of novel biologics and small-molecule Janus kinase (JAK) inhibitors, demonstrating how they attenuate eosinophilic inflammation. By identifying current gaps in this field, this review provides valuable insights for future research and clinical practice in the field of AD. Full article

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 (T2) asthma endotype. Emerging biomarkers, or older biomarkers with emerging utility, include sputum inflammatory cells (eosinophils, neutrophils, interleukins), thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, eosinophil peroxidase (EPX), Clara/club cell secretory protein (CC16), and quantitative computerized tomography (QCT) imaging biomarkers (evaluating mucus plugging, air trapping, airway wall thickness, small airway remolding) and are increasingly used in clinical trials as secondary endpoints in evaluating efficacy, as well as in the clinical setting at specialized centers. The rapid advances in asthma research, due in part to biomarkers and biologic therapies, may soon standardize an end goal: symptom-free asthma remission without exacerbations. Full article

Carbon fibre reinforced composite (CFRP) laminates are widely used in high-tech industries. However, their assembly often requires a drilling process that can create defects. Therefore, studies on the drill tip angle have sought to minimize the surface area affected by these defects and improve the internal hole quality. In this work, drilling was carried out under dry conditions at a constant cutting speed for four different feed rates in the epoxy–carbon-based thermosetting laminate (EPX-C). Two carbide drills with point angles of 118° and 140° were used. The results showed the occurrence of chipping-type delaminations on both the hole entry and exit surfaces, with the latter being more severely affected. The delamination factor values obtained indicated that the 118° drill performed better than the 140° drill. The results were also compared with those obtained in a previous study using drills with angles of 60° and 130°. Although the values were higher, they followed the same trend of reduction with increasing feed. In terms of surface finish, the average roughness (Ra) values obtained with the 140° drill were better at the lowest feed rate. Full article

Eosinophils, a type of granulocyte derived from myeloid precursors in the bone marrow, are distinguished by their cytoplasmic granules. They play crucial roles in immunoregulation, tissue homeostasis, and host defense, while also contributing to the pathogenesis of various inflammatory diseases. Although long non-coding RNAs (lncRNAs) are known to be involved in eosinophilic conditions, their specific expression and functions within eosinophils have not been thoroughly investigated, largely due to the reliance on tissue homogenates. In an effort to address this gap, we analyzed publicly available high-throughput RNA sequencing data to identify lncRNAs associated with eosinophilic conditions. Among the identified lncRNAs, ITGB2 antisense RNA 1 (ITGB2-AS1) was significantly downregulated in blood eosinophils from patients with hypereosinophilia. To further explore its role in eosinophil biology, we generated a stable ITGB2-AS1 knockdown in the HL-60 cell line. Interestingly, ITGB2-AS1 deficiency led to impaired eosinophil differentiation, as evidenced by a reduction in cytoplasmic granules and decreased expression of key eosinophil granule proteins, including eosinophil peroxidase (EPX) and major basic protein-1 (MBP-1). Additionally, ITGB2-AS1-deficient cells exhibited compromised eosinophil effector functions, with reduced degranulation and impaired production of reactive oxygen species (ROS). These findings suggest that ITGB2-AS1 plays a pivotal role in eosinophil differentiation and function, positioning it as a novel regulator in eosinophil biology. Full article

This paper experimentally investigates the behavior of innovative sustainable Low-Cost Bamboo Composite (LCBC) structural columns under compressive loading. The LCBC columns are manufactured from bamboo culms in combination with bio-based resins to form composite structural columns. Different LCBC cross-sectional configurations are investigated in this study, including the Russian doll (RD), Big Russian doll (BRD), Hawser (HAW), and Scrimber (SCR). Two bio-based resins, including one bio-epoxies and one furan-based resin, in addition to a soft bio-based filler and a synthetic epoxy resin, are applied. The bamboo species used as the cast-in-place giant bamboo for all configurations include Moso, Guadua, and Tali. Slender LCBC columns showed maximum stress equal to 60 MPa at failure. The study found that the samples with bio-epoxy resin (BE2) exhibited enhanced material stiffness when compared to synthetic epoxy (EPX) and furan-based resin (PF1), while PF1 specimens demonstrated increased ductility. Among the specimens with Moso bamboo and BE2 resin, those with SCR and HAW configurations achieved the highest compressive strengths. Full article

This paper investigates the effect of innovative cross-sectional configurations on Low-Cost Bamboo Composite (LCBC) structural members. The study employs both experimental and numerical methods with different resin matrices and bamboo species. In this study, LCBC short columns are designed with different innovative cross-sectional configurations in an attempt to overcome the costly production processes of engineered bamboo. This approach uses bundles of bamboo, both in culm and strip forms. A compatible, environmentally responsible, and economically justifiable resin matrix is used to fabricate an LCBC member. The production of LCBC members does not necessitate highly advanced technology. This capability enables the production of LCBC members in custom-designed cross-sectional shapes and lengths. This study introduces the Russian doll (RD), Big Russian doll (BRD), Hawser (HAW), and Scrimber (SCR) cross-sectional configurations. Extra-large, large, medium, and small sizes of bamboo are employed. Synthetic Epoxy (EXP), a Bio-based Experimental soft filler (BE1), Bio-Epoxy (BE2), Furan-based (PF1) matrices are applied. Furthermore, Moso, Guadua, Madake, and Tali bamboo species are incorporated. The results of this study reveal that the most efficient cross-sectional configuration for compressive strength is the HAW configuration, closely followed by the SCR configuration. LCBC members with bio-resins have shown excellent promise in competing in strength with those made with their synthetic counterparts. The maximum compressive strengths (MPa) were achieved by two specimens with synthetic epoxy closely followed by a specimen with bio-epoxy, namely HAW-EPX-M, RD-EPX-M, and RD-BE2-G specimens with 78 MPa, 75 MPa, and 72 MPa, respectively. In terms of the modulus of elasticity of LCBC with different resin matrices, the stiffest specimens were HAW-BE2-M1, HAW-EPX-M, and HAW-BE2-M2 with 3.89 GPa, 3.08 GPa, and 2.54 GPa, respectively. The theoretical and numerical modelling of the LCBC members showed excellent correlation with the experimental results, which provides the capacity to design LCBC for engineering projects. The LCBC design can be further developed with more bamboo and less resin content. Full article

Eosinophilic airway inflammation, complicated by bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), is difficult to treat. The disease may become refractory when eosinophilic mucin associated with eosinophil peroxidase (EPX) and autoantibodies fills in the paranasal sinus and small airway. This study investigated the functional role of an anti-EPX antibody in eosinophilic mucin of ECRS in eosinophilic airway inflammation. Eosinophilic mucin was obtained from patients with ECRS. The effects of the anti-EPX antibody on dsDNA release from eosinophils and eosinophilic mucin decomposition were evaluated. Immunofluorescence or enzyme-linked immunosorbent assays were performed to detect the anti-EPX antibody and its supernatant and serum levels in eosinophilic mucin, respectively. The serum levels of the anti-EPX antibody were positively correlated with sinus computed tomography score and fractionated exhaled nitrogen oxide. Patients with refractory ECRS had higher serum levels of the anti-EPX antibody than those without. However, dupilumab treatment decreased the serum levels of the anti-EPX antibody. Immunoglobulins (Igs) in the immunoprecipitate of mucin supernatants enhanced dsDNA release from eosinophils, whereas the neutralization of Igs against EPX stopped dsDNA release. Furthermore, EPX antibody neutralization accelerated mucin decomposition and restored corticosteroid sensitivity. Taken together, the anti-EPX antibody may be involved in the formulation of eosinophilic mucin and be used as a clinical marker and therapeutic target for intractable eosinophilic airway inflammation. Full article

Epoxiconazole (EPX), a triazole fungicide, is widely used in agriculture to control pests and diseases. High residual and occupational exposure to EPX increases health risks, and evidence of potential harm to mammals remains to be added. In the present study, 6-week-old male mice were exposed to 10 and 50 mg/kg bw EPX for 28 days. The results showed that EPX significantly increased the liver weights. EPX also decreased the mucus secretion of the colon and altered intestinal barrier function in mice including a reduced expression of some genes (Muc2, meprinβ, tjp1). Moreover, EPX altered the composition and abundance of gut microbiota in the colon of mice. The alpha diversity indices (Shannon, Simpson) in the gut microbiota increased after exposure to EPX for 28 days. Interestingly, EPX increased the ratio of Firmicutes to Bacteroides and the abundance of other harmful bacteria including Helicobacter and Alistipes. Based on the untargeted metabolomic analysis, it was found that EPX altered the metabolic profiles of the liver in mice. KEGG analysis of differential metabolites revealed that EPX disrupted the pathway related to glycolipid metabolism, and the mRNA levels of related genes were also confirmed. In addition, the correlation analysis showed that the most altered harmful bacteria were associated with some significantly altered metabolites. The findings highlight that EPX exposure changed the micro-environment and lipid metabolism disturbance. These results also suggest that the potential toxicity of triazole fungicides to mammals cannot be ignored. Full article

Measure of drug-mediated immune reactions that are dependent on the patient’s genotype determine individual medication protocols. Despite extensive clinical trials prior to the license of a specific drug, certain patient-specific immune reactions cannot be reliably predicted. The need for acknowledgement of the actual proteomic state for selected individuals under drug administration becomes obvious. The well-established association between certain HLA molecules and drugs or their metabolites has been analyzed in recent years, yet the polymorphic nature of HLA makes a broad prediction unfeasible. Dependent on the patient’s genotype, carbamazepine (CBZ) hypersensitivities can cause diverse disease symptoms as maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms or the more severe diseases Stevens-Johnson-Syndrome or toxic epidermal necrolysis. Not only the association between HLA-B*15:02 or HLA-A*31:01 but also between HLA-B*57:01 and CBZ administration could be demonstrated. This study aimed to illuminate the mechanism of HLA-B*57:01-mediated CBZ hypersensitivity by full proteome analysis. The main CBZ metabolite EPX introduced drastic proteomic alterations as the induction of inflammatory processes through the upstream kinase ERBB2 and the upregulation of NFκB and JAK/STAT pathway implying a pro-apoptotic, pro-necrotic shift in the cellular response. Anti-inflammatory pathways and associated effector proteins were downregulated. This disequilibrium of pro- and anti-inflammatory processes clearly explain fatal immune reactions following CBZ administration. Full article

Conventional epoxy polymers are thermo-set and difficult to recycle and reuse. In this study, a series of linear thermoplastic epoxy polymers (EPx) with shape memory properties were prepared by using a bifunctional monoamine diglycolamine (DGA) as a curing agent and an equivalent amount of bifunctional rigid epoxy resin (E-51) and bifunctional flexible epoxy resin (polypropylenglycol diglycidyl ether, PPGDGE) in a bulk polymerization reaction. The results showed that these samples can fully react under the curing process of, 60 °C/2 h, followed by 80 °C/2 h, followed by 120 °C/2 h. The introduction of different contents of PPGDGE can adjust the T_g of the material to adapt to different environmental requirements, and can significantly increase the fracture strain of the material and improve its micro-phase separation structure. Thus, R_f of the material is close to 100%, and R_r is increased from 87.98% to 97.76%. Importantly, this linear chain structure allows the material to be easily recycled and reprocessed by dissolving or melting, and also means the material shows potential for 3D printing or other thermoplastic remolding. Full article

The recent legalisation of hemp seeds for human consumption has revitalised the cultivation of hemp in Australia. This provides opportunities for the valorisation of the stem’s residual xylemic core (hemp hurd). This study investigated the effect of particle dimension and constituent proportions on the internal bond strength (IB) of single-layer, ultra-low-density hemp hurd particleboard (ULHPB) with densities between 219 to 304 kg/m³. Particle size distributions (PSD) and granulometry assessments were conducted on three particle size classes (fine (F), medium (M), coarse (C)) based on digital image analysis using ImageJ. Subsequently, four particle size mixes (100% C, 100% M, 50/50% CM, 25/50/25% CMF) were considered for the ULHPB manufacture with bio-epoxy (EPX), phenol resorcinol formaldehyde (PRF) and emulsifiable methylene diphenyl diisocyanate (MDI) adhesives, respectively. The effect of particle loading and adhesive content varied significantly per adhesive type. Internal bond (IB) performance increased in most ULHPB comprising coarse particles and declined with the addition of smaller particle sizes. The granulometry assessment showed the smallest mean elongation amongst particles in the coarse PSD. The IB results confirmed a strong interdependence of particle size and constituent proportions and indicated that various MDI-ULHPB variants can surpass the minimum IB strength requirement of 0.30 MPa stipulated for standard particleboard (>12–22 mm) in AS/NZS 1859.1. Utilising residual hemp biomass as an alternative, renewable lignocellulosic feedstock in the manufacture of engineered lightweight panel products is a key principle of circular economy and an environmentally friendly strategy to address the increasing resource scarcity in the wood-based panel industry. Full article

Immune checkpoint inhibition (ICI) has yielded remarkable results in prolonging survival of metastatic melanoma patients but only a subset of individuals treated respond to therapy. Success of ICI treatment appears to depend on the number of tumor-infiltrating effector T-cells, which are known to be influenced by activated eosinophils. To verify the co-occurrence of activated eosinophils and T-cells in melanoma, immunofluorescence was performed in 285 primary or metastatic tumor tissue specimens from 118 patients. Moreover, eosinophil counts and activity markers such as eosinophil cationic protein (ECP) and eosinophil peroxidase (EPX) were measured in the serum before therapy start and before the 4th infusion of ICI in 45 metastatic unresected melanoma patients. We observed a positive correlation between increased tumor-infiltrating eosinophils and T-cells associated with delayed melanoma progression. High baseline levels of eosinophil count, serum ECP and EPX were linked to prolonged progression-free survival in metastatic melanoma. Our data provide first indications that activated eosinophils are related to the T-cell-inflamed tumor microenvironment and could be considered as potential future prognostic biomarkers in melanoma. Full article

Eosinophilic airway inflammatory disease is associated with bronchial asthma, with eosinophilic chronic rhinosinusitis (ECRS) typical of refractory type 2 airway inflammation. CCL4 produced at local inflammatory sites is involved in them via the accumulation and activation of type 2 inflammatory cells, including eosinophils. The detailed mechanism of CCL4 production remains unclear, and also the possibility it could function as a biomarker of type 2 airway inflammation remains unresolved. In this study, we evaluated CCL4 mRNA expression and production via the TSLP receptor (TSLPR) and toll-like receptors (TLRs) or proteinase-activated receptor-2 (PAR2) in BEAS-2B bronchial epithelial cells co-incubated with purified eosinophils or eosinophil peroxidase (EPX). We examined serum chemokine (CCL4, CCL11, CCL26, and CCL17) and total IgE serum levels, fractionated exhaled nitrogen oxide (FENO), and CCL4 expression in nasal polyps in patients with severe ECRS and asthma. CCL4 was induced by TSLP under eosinophilic inflammation. Furthermore, CCL4 was released via TLR3 signaling, which was enhanced by TSLP. CCL4 was mainly located in nasal polyp epithelial cells, while serum CCL4 levels were reduced after dupilumab treatment. Serum CCL4 levels were positively correlated with FENO, serum IgE, and CCL17 levels. Thus, CCL4 released from epithelial cells via the innate immune system during type 2 airway inflammation may function as a useful biomarker for the condition. Full article

Eosinophils are a subset of granulocytes characterized by a high abundance of specific granules in their cytoplasm. To act as effector cells, eosinophils degranulate and form eosinophil extracellular traps (EETs), which contain double-stranded DNA (dsDNA) co-localized with granule proteins. The exact molecular mechanism of EET formation remains unknown. Although the term “EET release” has been used in scientific reports, it is unclear whether EETs are pre-formed in eosinophils and subsequently released. Moreover, although eosinophil degranulation has been extensively studied, a precise time-course of granule protein release has not been reported until now. In this study, we investigated the time-dependent release of eosinophil peroxidase (EPX) and mitochondrial DNA (mtDNA) following activation of both human and mouse eosinophils. Unexpectedly, maximal degranulation was already observed within 1 min with no further change upon complement factor 5 (C5a) stimulation of interleukin-5 (IL-5) or granulocyte/macrophage colony-stimulating factor (GM-CSF)-primed eosinophils. In contrast, bulk mtDNA release in the same eosinophil populations occurred much slower and reached maximal levels between 30 and 60 min. Although no single-cell analyses have been performed, these data suggest that the molecular pathways leading to degranulation and mtDNA release are at least partially different. Moreover, based on these data, it is likely that the association between the mtDNA scaffold and granule proteins in the process of EET formation occurs in the extracellular space. Full article

N-retinylidene-N-retinylethanolamine (A2E) accumulation in the retina is a prominent marker of retinal degenerative diseases. Blue light exposure is considered as an important factor contributing to dry age-related macular degeneration (AMD). Eggplant and its constituents have been shown to confer health benefits, but their therapeutic effects on dry AMD remain incompletely understood. In this study, we showed that an extract of Solanum melongena L. (EPX) protected A2E-laden ARPE-19 cells against blue light-induced cell death via attenuating reactive oxygen species. Transcriptomic analysis demonstrated that blue light modulated the expression of genes associated with stress response, inflammation, and cell death, and EPX suppressed the inflammatory pathway induced by blue light in A2E-laden ARPE-19 cells by inhibiting the nuclear translocation of nuclear factor kappa B and transcription of pro-inflammatory genes (CXCL8 and IL1B). The degradation of intracellular A2E was considered the major mechanism underlying the protective effect of EPX. Moreover, chlorogenic acid isolated from EPX exerted protective effects against blue light-induced cell damage in A2E-laden ARPE-19 cells. In vivo, EPX administration in BALB/c mice reduced the fundus damage and degeneration of the retinal layer in a blue light-induced retinal damage model. Collectively, our findings suggest the potential role of Solanum melongena L. extract for AMD treatment. Full article