Search Results (32)

Numerous studies have demonstrated that Broussonetia papyrifera is an unconventional feed resource with significant developmental potential. This research aimed to explore the effects of Broussonetia papyrifera silage on the growth performance, blood parameters, immunity, antioxidation, cytokine levels, and rumen bacterial composition of Kazakh lamb. Forty healthy male Kazakh lambs, aged 5 months and weighing 30.12 ± 1.14 kg, were randomly divided into control and experimental groups, each consisting of four replicates (five lambs per replicate). The control group was fed a basal diet, while the experimental group received a diet supplemented with 20% Broussonetia papyrifera silage (dry matter basis). Following a 10-day pre-feeding period, a 60-day formal experiment was conducted. The results indicated no significant difference in growth performance between the experimental and control groups. However, compared to the control group, the use of Broussonetia papyrifera silage significantly reduced (p < 0.05) neutrophil, lymphocyte, and eosinophil counts, as well as creatinine levels in the blood. Furthermore, Broussonetia papyrifera silage (p < 0.01) enhanced total serum antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, immunoglobulin A, immunoglobulin M, immunoglobulin G, interleukin-2, interleukin-6, and interleukin-8, and decreased malondialdehyde and interleukin-4 levels. Additionally, the use of Broussonetia papyrifera silage increased the diversity and richness of the rumen bacterial community, notably enhancing the relative abundance of Firmicutes such as Rikenellaceae_RC9_gut_group and Christensenellaceae_R-7_group. In conclusion, feeding Kazakh lamb with Broussonetia papyrifera silage (20% DM) did not adversely affect their growth performance but improved their immunity and antioxidant capacity and enhanced the relative abundance of beneficial bacteria in the rumen, thereby promoting animal health. 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

The lockdown imposed to combat the COVID-19 pandemic produced a historic fall in air pollution in cities like Barcelona. This exceptional situation offered a unique context in which to examine the effects of air pollutants on human health. The present study aims to determine and compare the oxidative stress biomarkers Th1/Th2 and inflammatory-related cytokines in healthy individuals first during lockdown and then six months after the easing of the restrictions on mobility. A prospective study of a representative sample of 58 healthy, non-smoking adults was carried out. During lockdown and six months post-easing of restrictions, blood samples were drawn to measure the percentage of eosinophils, levels of Th1/Th2 and inflammatory-related cytokines assessed by a multiplex assay (BioRad Laboratories S.A., Marnes-la-Coquette, France), and levels of 8-isoprostane, glutathione peroxidase activity, and myeloperoxidase (Cayman Chemical Co., Ann Arbor, MI, USA), to assess their value as biomarkers of oxidative stress. Six months after easing mobility restrictions, increases in the levels of 8-isoprostane (p < 0.0001), IL-1β (p = 0.0013), IL-1ra (p = 0.0110), IL-4 (p < 0.0001), IL-13 (p < 0.0001), G-CSF (p = 0.0007), and CCL3 (p < 0.0001) were recorded, along with reductions in glutathione peroxidase (p < 0.0001), IFN-γ (p = 0.0145), TNFα (p < 0.0001), IP-10 (p < 0.0001), IL-2 (p < 0.0001), IL-7 (p < 0.0001), basic FGF (p < 0.0001), CCL4 (p < 0.0001), and CCL5 (p < 0.0001). No significant differences were observed in the rest of the biomarkers analyzed. The reduction in environmental pollution during the COVID-19 lockdown significantly lowered the levels of oxidative stress, systemic inflammation, and Th2-related cytokines in healthy people. Full article

Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was significantly higher in the lungs of IAV-infected sows compared to healthy pigs, indicating a migration of eosinophils from blood vessels into the lung tissue stimulated by IAV infection. The detection of intra- and extracellular EPO in the lungs suggests its contribution to pulmonary damage. The presence of CD3⁺ T lymphocytes, CD20⁺ B lymphocytes, and Iba-1⁺ macrophages indicates the involvement of cell-mediated immune responses in disease progression. Furthermore, high numbers of myeloperoxidase-positive cells were detected. However, DNA-histone-1 complexes were reduced in IAV-infected sows, leading to the hypothesis that NETs are not formed in the IAV-infected sows. In conclusion, our findings in the lungs of IAV-infected vaccinated sows suggest the presence of so far unreported field cases of vaccine-associated enhanced respiratory disease. Full article

Inhalation represents a significant route of cadmium (Cd) exposure, which is associated with an elevated risk of lung diseases. This research study aims to evaluate the impact of repeated low-dose cadmium inhalation on exacerbating airway inflammation induced by ovalbumin (OVA) in asthma-afflicted mice. Mice were grouped into four categories: control (Ctrl), OVA, cadmium chloride (CdCl₂), and OVA + cadmium chloride (OVA + CdCl₂). Mice in the OVA group displayed increased airway mucus secretion and peribronchial and airway inflammation characterized by eosinophil cell infiltration, along with elevated levels of Th2 cytokines (IL-4, IL-5, IL-13) in bronchoalveolar lavage fluids (BALFs). These parameters were further exacerbated in the OVA + CdCl₂ group. Additionally, the OVA + CdCl₂ group exhibited higher levels of the oxidative stress marker malondialdehyde (MDA), greater activity of glutathione peroxidase (GSH-Px), and higher phosphorylation of extracellular regulated kinase (ERK) in lung tissue. Treatment with U0126 (an ERK inhibitor) and α-tocopherol (an antioxidant) in the OVA + CdCl₂ group resulted in reduced peribronchial and airway inflammation as well as decreased airway mucus secretion. These findings indicate that CdCl₂ exacerbates airway inflammation in OVA-induced allergic asthma mice following airway exposure. ERK and oxidative stress are integral to this process, and the inhibition of these pathways significantly alleviates the adverse effects of CdCl₂ on asthma exacerbation. Full article

In the present work, we evaluated the antifungal activities of two novel ebselen analogs, N-allyl-benzisoselenazol-3(2H)-one (N-allyl-bs) and N-3-methylbutylbenzisoselenazol-3(2H)-one (N-3mb-bs). Colorimetric and turbidity assays were performed to determine the minimum inhibitory concentration (MIC) of these compounds in S1 (fluconazole-sensitive) and S2 (fluconazole-resistant) strains of C. albicans. N-3mb-bs was more active than the N-allyl-bs compound. It is noteworthy that the concentration of N-3mb-bs observed to inhibit fungal growth by 50% (18.2 µM) was similar to the concentration observed to inhibit the activity of the yeast plasma membrane H⁺-ATPase (Pma1p) by 50% (19.6 µM). We next implemented a mouse model of vulvovaginal candidiasis (VVC) using the S1 strain and examined the mouse and yeast proteins present in the vaginal lavage fluid using proteomics. The yeast proteins detected were predominately glycolytic enzymes or virulence factors associated with C. albicans while the mouse proteins present in the lavage fluid included eosinophil peroxidase, desmocollin-1, and gasdermin-A. We then utilized the N-3mb-bs compound (12.5 mg/kg) in the mouse VVC model and observed that it significantly reduced the vaginal fungal burden, histopathological changes in vagina tissue, and expression of myeloperoxidase (MPO). All in all, the present work has identified a potentially promising drug candidate for VVC treatment. Full article

Human peroxidasin (PXDN) is a ubiquitous peroxidase enzyme expressed in most tissues in the body. PXDN represents an interesting therapeutic target for inhibition, as it plays a role in numerous pathologies, including cardiovascular disease, cancer and fibrosis. Like other peroxidases, PXDN generates hypohalous acids and free radical species, thereby facilitating oxidative modifications of numerous biomolecules. We have studied the inhibition of PXDN halogenation and peroxidase activity by phloroglucinol and 14 other peroxidase inhibitors. Although a number of compounds on their own potently inhibited PXDN halogenation activity, only five were effective in the presence of a peroxidase substrate with IC₅₀ values in the low μM range. Using sequential stopped-flow spectrophotometry, we examined the mechanisms of inhibition for several compounds. Phloroglucinol was the most potent inhibitor with a nanomolar IC₅₀ for purified PXDN and IC₅₀ values of 0.95 μM and 1.6 μM for the inhibition of hypobromous acid (HOBr)-mediated collagen IV cross-linking in a decellularized extracellular matrix and a cell culture model. Other compounds were less effective in these models. Most interestingly, phloroglucinol was identified to irreversibly inhibit PXDN, either by mechanism-based inhibition or tight binding. Our work has highlighted phloroglucinol as a promising lead compound for the design of highly specific PXDN inhibitors and the assays used in this study provide a suitable approach for high-throughput screening of PXDN inhibitors. 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

This study examined the impact of dietary limonene treatment on the growth performance, immune response, and disease resistance of common carp, Cyprinus carpio. The fish were fed with either a control diet (CTL; no limonene supplementation) or four experimental diets containing 50 (50 L), 100 (100 L), 200 (200 L), and 400 (400 L) mg/kg limonene over a 70-day period, followed by Aeromonas hydrophila challenge. The 200 L treatment resulted in a significant decrease in FCR compared to the CTL treatment. The highest post-challenge mortality was associated with the CTL treatment (62.7%), while the 200 L treatment had the lowest mortality (30.7%). Before the challenge, dietary limonene significantly increased humoral and skin mucosal immune parameters compared to the CTL treatment. The highest leukocyte, lymphocyte counts, skin mucosal protease activity, and intestinal lactic acid bacteria were observed in the 200 L treatment before the challenge. The highest plasma lysozyme activity was observed in the 400 L treatment, whereas the highest skin mucosal lysozyme and peroxidase activities were observed in the 100 L and 200 L treatments before the challenge. There were no significant differences in the blood neutrophil, monocyte, and eosinophil counts, humoral alternative complement activity, skin mucosal alkaline phosphatase activity, and the intestinal total viable bacteria among the treatments before the challenge. After the challenge, the 200 L treatment exhibited the highest leukocyte, neutrophil, and monocyte count, skin mucosal immune parameters, and intestinal lactic acid bacteria, whereas the highest blood eosinophil count was observed in the 100 L, 200 L, and 400 L treatments. At this time, the lowest blood lymphocyte counts were observed in the 100 L and 200 L, but the lowest intestinal total viable bacteria were observed in the 100 L, 200 L, and 400 L treatments. Based on these findings, dietary limonene at 200 mg/kg is ideal for common carp to promote feed efficiency, innate immunity boosting, and resistance against A. hydrophila. Full article

Eosinophilic esophagitis (EoE) is a chronic esophageal disease that needs lifelong management and follow-up. The diagnosis requires an upper endoscopy with at least one esophageal biopsy demonstrating >15 eosinophils/high-power field, and often occurs with a diagnostic delay of up to ten years, partly due to the absence of valid non-invasive screening tools. In addition, serial upper endoscopies with esophageal biopsies are mandatory to assess the efficacy of any ongoing treatment in patients with EoE. These procedures are invasive, costly, and, when performed without sedation, are often poorly tolerated by patients. Therefore, there is the clinical need to identify reliable non-invasive or minimally invasive biomarkers that could be used to assess disease activity in clinical practice as a surrogate of peak eosinophil counts on esophageal biopsies. This review summarizes evidence on investigational non-invasive or minimally invasive biomarkers for the diagnosis and follow-up of EoE to report on the state of the art in the field and support future research. We discussed eosinophil-derived mediators including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN, also known as eosinophil protein X), eosinophil peroxidase (EPO), and major basic protein (MBP) as well as other promising non-eosinophil-derived biomarkers. Although several studies have shown the utility of most biomarkers collected from the serum, esophageal luminal secretions, and feces of EoE patients, numerous limitations currently hamper the integration of such biomarkers in clinical practice. Future studies should aim at validating the utility of non-invasive and minimally invasive biomarkers using rigorous protocols and updated consensus criteria for EoE. Full article

Several pieces of evidence point to an allergic component as a trigger of acute appendicitis. As the Th2 immune response is characterized by eosinophil mobilization to the target organ and release of their cationic granule proteins, it is reasonable to investigate if the degranulation of eosinophils could be associated with the local injury. The primary aim of this study is to evaluate the participation of eosinophils granules proteins in acute appendicitis, both at local and systemic levels and the secondary aim is to evaluate the diagnostic accuracy of eosinophils granules proteins for the detection of acute appendicitis, as well as for distinguishing between complicated and uncomplicated acute appendicitis. Eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and eosinophil peroxidase (EP) are the most well-known eosinophil granule proteins. From August 2021 to April 2022, we present a prospective single-center study to evaluate the EDN, ECP, and EP concentrations simultaneously in appendicular lavage fluid (ALF) and the serum of 22 patients with acute phlegmonous appendicitis (APA), 24 with acute gangrenous appendicitis (AGA), and 14 normal controls. Concerning EDN, no differences were found between groups. ECP concentrations in ALF and serum were significantly higher in the histologically confirmed acute appendicitis compared to the control groups (p < 0.0001 and p < 0.0001, respectively). In ALF, no differences were found between ECP levels in APA: 38.85 ng/mL (IQR 26.50–51.77) and AGA 51.55 ng/mL (IQR 39.55–70.09) groups (p = 0.176). In the serum, no difference was found between ECP levels at APA: 39 ng/mL (IQR 21.30–56.90) and AGA: 51.30 ng/mL (IQR 20.25–62.59) (p = 0.100). For EP, the concentrations in ALF (p < 0.001) and serum (p < 0.001) were both higher in acute appendicitis compared to the control. In ALF, no difference was found between APA: 240.28 ng/mL (IQR 191.2–341.3) and AGA: 302.5 (IQR 227.7–535.85) (p = 0.236). In the serum, no differences were found between APA: 158.4 ng/mL (IQR 111.09–222.1) and AGA: 235.27 (IQR 192.33–262.51) (p = 0.179). Globally, the ALF concentrations were higher than serum concentrations, reflecting an intense inflammatory local reaction in AA. The optimal ECP cut-off for discriminating between acute appendicitis and the controls was >11.41 ng/mL, with a sensitivity of 93.5%, but with a specificity for identifying appendicitis of 21.4%, good discriminative power (AUC = 0.880). For EP, the optimal cut-off was >93.20 ng/mL, with a sensitivity of 87%, but with a specificity of 14.3% (AUC = 0.901), excellent discriminative power. For the diagnosis of perforated AA, the discriminative power of ECP and EP serum concentrations are weak (AUC = 0.562 and AUC = 0.664, respectively). Concerning the presence of peritonitis, the discriminative power of ECP and EP serum concentrations is acceptable, respectively: AUC = 0.724 and AUC = 0.735. Serum levels of EDN (p = 0.119), ECP (p = 0.586) and EP (p = 0.08) in complicated appendicitis were similar to uncomplicated appendicitis. Serum concentrations of ECP and EP can be added to decision-making AA diagnosis. A Th2-type immune response is present in AA. These data bring forward the role of an allergic reaction in the pathogenesis of acute appendicitis. Full article

Glyphosate is an active ingredient in herbicides. Exposure to glyphosate-based herbicides has been associated with respiratory dysfunctions in agricultural workers. The ability of inhaled glyphosate to induce lung inflammation is not well understood. Further, the role of adhesion molecules in glyphosate-induced lung inflammation has not been studied. We evaluated lung inflammatory responses from single and repeated glyphosate exposures. Male C57BL/6 mice were intranasally exposed to glyphosate (1 μg/40 μL) for 1 day or once daily for 5 days or 10 days. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected and analyzed. Repeated exposure to glyphosate for 5 days and 10 days resulted in an increase in neutrophils in BAL fluid and higher eosinophil peroxidase levels in lungs, with leukocyte infiltration further confirmed through lung histology. Repetitive exposure to glyphosate increased IL-33 and Th2 cytokines IL-5 and IL-13. A single glyphosate treatment revealed expression for ICAM-1, VCAM-1, and vWF adhesion molecules in the perivascular region of lung sections; with repeated treatment (5 and 10 days), adhesion molecule expression was found in the perivascular, peribronchiolar, and alveolar regions of the lungs. Repetitive exposure to glyphosate induced cellular inflammation in which adhesion molecules may be important to the lung inflammatory process. Full article

The effects of dietary glycine supplementation, 0 (control), 5 (5 GL), and 10 (10 GL) g/kg, have been investigated on growth performance, hematological parameters, erythrocyte antioxidant capacity, humoral and mucosal immunity in common carp, Cyprinus carpio. After eight weeks feeding, the 5 GL treatment exhibited significant improvement in growth performance and feed efficacy, compared to the control treatment. Red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin, hematocrit, neutrophil and monocyte counts/percentages, RBC reduced glutathione (GSH) content, and skin mucosal alkaline phosphatase, peroxidase, protease, and lysozyme activities were similar in the glycine-treated fish and significantly higher than the control treatment. Blood lymphocyte percentage decreased in the glycine-treated fish, but lymphocyte count increased, compared to the control fish. RBC glutathione reductase activities in the glycine-treated fish were similar and significantly lower than the control treatment. The highest plasma lysozyme and alternative complement activities were observed in GL treatment. The glycine-treated fish, particularly 5 GL, exhibited significant improvement in RBC osmotic fragility resistance. Dietary glycine had no significant effects on RBC glutathione peroxidase activity, plasma immunoglobulin, eosinophil percentage/count, and hematological indices. In conclusion, most of the benefits of dietary glycine supplementation may be mediated by increased glutathione synthesis and antioxidant power. 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

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1β and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition. Full article