Eosinophils Research Articles

Виявлення замаскованої харчової алергії в дітей, хворих на бронхіальну астму, за допомогою констеляційного методу

На підставі клініко-імунологічного обстеження 100 пацієнтів, хворих на бронхіальну астму, вивчено особливості її перебігу на тлі харчової алергії. Встановлено, що найбільш значимими відмінностями цих дітей були обтяжений сімейний алергологічний анамнез, наявність патології антенатального періоду, негативний резерв киснезалежної мікробіцидності еозинофільних гранулоцитів крові. Указані характеристики дозволили сформувати діагностичну констеляційну таблицю для виявлення замаскованої харчової алергії в дітей з бронхіальною астмою для оптимізації лікувально-реабілітаційних заходів.

Black soldier fly meal effects on meagre health condition: gut morphology, gut microbiota and humoral immune response

The effects of black soldier fly (Hermetia illucens) meal (HM) on gut morphology, gut microbial community, and humoral immune response was evaluated in meagre (Argyrosomus regius) juveniles. For that purpose, fish with 18.0±0.02 g were fed a control diet (CTR) without HM, and 3 other diets including 10, 20 and 30% HM (diets HM10, HM20 and HM30, respectively), replacing 17, 35 and 52% of fish meal (FM), for 9 weeks. The meagre distal intestine (DI) showed no significant histomorphologic alterations in fold height, lamina propria, submucosa width and cellularity, and enterocytes shape, between dietary treatments. Increasing numbers of eosinophilic granulocytes and intraepithelial leukocytes were observed in fish fed the HM30 diet compared to the CTR and HM10 diets. The mean DI score was higher in meagre fed the HM30 diet, denoting increased overall histomorphological alterations in that group compared to fish fed the CTR diet. No differences in gut bacterial profiles (number of operational taxonomic units, microbiota richness, diversity, and similarity indices) were observed between dietary treatments, either in allochthonous (digesta) and autochthonous (mucosa) communities. Plasma anti-protease activity increased with increasing dietary HM level, while no significant differences were observed in the plasmatic protease, peroxidase, lysozyme and bactericidal activities, nitric oxide production and total immunoglobulins. Overall, and in order to avoid gut histomorphological alterations, an inclusion level up to 10% of HM, corresponding to 17% of FM replacement, is recommended for meagre juveniles.

Acupuncture Alleviates Menstrual Pain in Rat Model via Suppressing Eotaxin/CCR3 Axis to Weak EOS-MC Activation.

Introduction Emerging data show that chemokine-mediated inflammation is involved in the occurrence and maintenance of pain. Recent evidence suggests that eotaxin levels rise when dysmenorrhea happens. The purpose of this study is to investigate whether eotaxin/CC chemokine receptor 3 (CCR3) axis, a key regulatory pathway for eosinophils (EOS) recruitment, is involved in acupuncture analgesia for dysmenorrhea. Methods After the cold congealing dysmenorrhea (CCD) rat model prepared, animals received perpendicular needling (PN) and transverse needling (TN) at SP6, respectively, for 20 min. The CCR3 agonist CCL11 was administered 30 min prior to acupuncture. Pain behavior was assessed via a writhing response. The uterine contraction test was detected by an electrophysiological method. Eotaxin, histamine (HIS), and interleukin-6 (IL-6) levels were evaluated by ELISA. The expression of CCR3 and histamine H1 receptor (H1R) was analyzed by RT-qPCR and Western blot. The expression of EOS, mast cells (MCs), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP) was assessed by hematoxylin-eosin staining (HE), Toluidine Blue staining (TB), and immunohistochemistry, respectively. Results Acupuncture prominently attenuated the menstrual pain in CCD rats, particularly TN technique. Electrophysiological recording data showed that the increased uterine contractility was ameliorated by acupuncture. In addition, TN decreased the release of eotaxin, HIS, IL-6, and the expression of CCR3 and H1R. HE, TB staining, and immunohistochemistry experiments showed that the increased expression of EOS, MCs, EPO, and ECP in uterine tissues was reversed by TN. Furthermore, we found that the effects of TN against CCD-induced menstrual pain, increased ECP expression, and HIS level were abolished by CCL11. Conclusion TN alleviated menstrual pain by improving the uterine inflammatory environment via suppressing eotaxin/CCR3 axis to weak EOS-MC activation in CCD rats. The study findings support the acupuncture as a promising approach for dysmenorrhea, meanwhile, indicating the importance of performing appropriate needling technique.

CCR3 gene knockout in bone marrow cells ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing airway inflammatory cell infiltration and Th2 cytokines expression in mice model

The present study aims to investigate the effects of CCR3 gene knockout in bone marrow cells (CCR3-KO) on the mouse model of combined allergic rhinitis and asthma syndrome (CARAS). It was found that CCR3-KO significantly reduced eosinophil (EOS) migration into the nasal (NALF) and bronchoalveolar (BALF) cavities of mice, and decreased Th2 cytokines (such as, IL-4, IL-5 and IL-13) levels in nasal mucosa and lung tissues. In addition, histological analysis showed that the damage degree of nasal mucosa structure in ovalbumin (OVA) modulated CCR3-KO mice was significantly less than that in OVA modulated Wild type (WT) mice, with reduced inflammatory cell infiltration and nasal mucus secretion. The infiltration of inflammatory cells in lung tissue was significantly reduced, and the proliferation of lung smooth muscle layer and extracellular matrix (ECM) production were decreased. Symptom analysis showed that CCR3-KO can reduced allergic rhinitis (AR) signals as nose scratching and sneezing. It was also found CCR3-KO reduce OVA-induced weight loss. The results showed that CCR3-KO could reduce the symptoms of allergic inflammation in CARAS mice by reducing airway inflammatory cell infiltration and down-regulating the expression of Th2 cytokines, and CCR3 gene could be used as a target gene for the treatment of CARAS.

Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners.

High eosinophil (EOS) counts are a key feature of eosinophilic asthma. EOS notably affect asthmatic response by generating several lipid mediators. Mice have been utilized in hopes of defining new pharmacological targets to treat asthma. However, many pinpointed targets in mice did not translate into clinics, underscoring that key differences exist between the two species. In this study, we compared the ability of human (h) and mouse (m) EOS to biosynthesize key bioactive lipids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). hEOS were isolated from the blood of healthy subjects and mild asthmatics, while mEOSs were differentiated from the bone marrow. EOSs were treated with fatty acids and lipid mediator biosynthesis assessed by LC-MS/MS. We found that hEOS biosynthesized leukotriene (LT) C4 and LTB4 in a 5:1 ratio while mEOS almost exclusively biosynthesized LTB4. The biosynthesis of the 15-lipoxygenase (LO) metabolites 15-HETE and 12-HETE also differed, with a 15-HETE:12-HETE ratio of 6.3 for hEOS and 0.727 for mEOS. EOS biosynthesized some specialized pro-resolving mediators, and the levels from mEOS were 9-times higher than those of hEOS. In contrast, hEOS produced important amounts of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) and its congeners from EPA and DHA, a biosynthetic pathway that was up to ~100-fold less prominent in mEOS. Our data show that hEOS and mEOS biosynthesize the same lipid mediators but in different amounts. Compared to asthmatics, mouse models likely have an amplified involvement of LTB4 and specialized pro-resolving mediators and a diminished impact of the endocannabinoid 2-arachidonoyl-glycerol and its congeners.

Effect of Methylprednisolone Plus Azithromycin on Fractional Exhaled Nitric Oxide and Peripheral Blood Eosinophils in Children with Refractory Mycoplasma Pneumoniae Pneumonia.

To investigate the efficacy and adverse reactions of methylprednisolone plus azithromycin in the treatment of children with refractory mycoplasma pneumoniae pneumonia (RMPP) and its effect on fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophils (EOS). Comparative study. Daqing Oilfield General Hospital, China, from June 2019 to January 2021. A total of 102 children with RMPP were randomly divided into Group A (n = 51) and Group B (n = 51) by the random number table. Group A was treated with azithromycin alone, and Group B was treated with methylprednisolone plus azithromycin. The efficacy, adverse reactions, FeNO and EOS levels were compared. The total effective rate of treatment in Group B was higher than that in Group A (p=0.006). Time of cough disappearance, lung shadow disappearance, defervescence and hospitalisation in Group B was shorter than that in Group A (p=0.033, 0.008, 0.004 and <0.001, respectively). After treatment, the FeNO and EOS levels in Group B were lower than those in Group A (both p <0.001). The efficacy of methylprednisolone plus azithromycin in treatment of RMPP is better than azithromycin alone. The former can reduce the levels of FeNO and EOS more effectively than the latter. Key Words: Refractory mycoplasma pneumoniae pneumonia (RMPP), Methylprednisolone, Azithromycin, Fractional exhaled nitric oxide (FeNO), Eosinophils (EOS).

Effects of budesonide combined with salbutamol on pulmonary function and peripheral blood eosinophiles and IgE in patients with acute attack of bronchial asthma.

Objectives:To explore the effect and value of salbutamol and budesonide in the treatment of patients with acute attack of bronchial asthma.Methods:Medical records of patients with acute attack of bronchial asthma treated in our hospital from February 2020 to March 2021 were retrospectively analyzed. Of them, 30 patients received salbutamol atomization inhalation treatment in addition to routine treatment such as cough relief, oxygen inhalation and asthma relief (Group-I), and 40 patients received routine treatment and budesonide and salbutamol atomization inhalation (Group-II). The time of symptom improvement, the improvement in pulmonary function indexes and in peripheral blood eosinophile (EOS) and IgE levels were retrospectively analyzed and compared between the two schemes.Results:After the treatment, the average time of respiratory restriction, cough, shortness of breath and wheezing improvement in patients, treated with Group-II were lower than those in Group-I (P<0.05). Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) in Group-II were significantly higher than those in Group-I (P<0.05). Post treatment levels of EOS and IgE in peripheral blood of Group-II were significantly lower than those of Group-I (P<0.05).Conclusion:On the basis of routine treatment, budesonide combined with salbutamol atomization inhalation for the treatment of patients with acute attack of asthma can be more efficient in improving symptoms and pulmonary, function and promote the effective reduction of EOS and IgE levels in peripheral blood.

Flavin Adenine Dinucleotide (FAD) Pegylated (PEG)-Complexes: Proof of Concept (PoC) of theranostic tool on a Murine Breast Cancer Model.

Flavin adenine dinucleotide (FAD) plays a key role in an extensive range of cellular oxidation-reduction reactions, which is engaged in metabolic pathways. The purpose of this study was to realize pegylated flavins formulation, named FAD and FAD-PEG diacid complex as theranostic tool in cancer therapy. For this objective, a murine breast cancer model, which was induced by mouse-derived4T1 breast cancer cells was studied to assess the therapeutic efficacy of FAD (named NP1) and FAD-PEG diacid complex (named NP2). The cytokines were monitored to evaluate the serum inflammatory factors to develop the blood cell content of different groups of nude mice. The experimental model shows that an intravenous injection of FAD (NP1) can significantly reduce tumour volume, tumour index and thymus index, and decrease neutrophils (NE), monocytes (MO), eosinophils (EO), and basophils (BA). At the same time, the content of IL-1α, IL-12P70, TNF α, IL-1β and IL-6 was significantly reduced, and the content of IL-10 was significantly increased. These results provide the proof-of-concept for FAD as a smart adjuvant for cancer therapy and encourages their further development in the field of Nanomedicine.

Expression and clinical significance of IL-33 and its receptor ST2 in children with obstructive sleep apnea syndrome.

BackgroundObstructive sleep apnea syndrome (OSAS) is characterized by a majority population of respiratory sleep disorders, which consists of simple snoring as well as increased upper airway resistance syndrome. Adenoid hypertrophy has been suggested as the main cause of OSAS in children. The role of interleukin-33 (IL-33) and its receptor suppressor of tumorigenicity 2 (ST2) in a variety of pediatric allergic diseases has been confirmed. We hypothesized that IL-33/ST2 path way might play a pivotal role in the pathogenesis of adenoid hypertrophy-associated OSAS in children.MethodsA total of 40 children undergoing adenoidectomy due to OSAS in the Otolaryngology of Tianjin Children’s Hospital were selected as the study participants. The quantity of IL-33 and ST2 positive cells in adenoids was detected by immunohistochemical (IHC) streptavidin-peroxidase conjugate (SP) method.ResultsThe IL-33 positive cells were mainly distributed in the submucosa epithelium and vascular endothelium, and expressed in the nucleus and cytoplasm. Meanwhile, ST2 positive cells were primarily observed in the mucosa and expressed in the nucleus and cytoplasm, with a little expression of intercellular substance. There was a positive correlation between the proportion of adenoids in the posterior nostril diameter and the number of IL-33 positive cells. The expression of IL-33 in adenoids was positively correlated with the level of ST2 (r=0.809, P=0.000). The expression of IL-33 in adenoids was positively correlated with the level of eosinophil granulocyte (r=0.859, P=0.000). Moreover, the expression of ST2 in adenoids was positively correlated with the level of eosinophil granulocyte (r=0.814, P=0.000). The number of IL-33 positive cells was significantly higher in the moderate hypoxemia group than that in the mild hypoxemia group (P<0.05). There was no significant difference in the number of ST2 positive cells between the moderate hypoxemia group and mild hypoxemia group (P>0.05).ConclusionsBoth IL-33 and its receptor ST2 were expressed in adenoids of OSAS children. The severity of airway obstruction caused by adenoid hypertrophy was positively correlated with the expression of IL-33.

A Herbal Concoction of Cinnamomum cassia and Artemisa annua Extracts Ameliorates Allergic Rhinitis in OVA-Induced Balb/C Mice by Inhibiting Th2 Signaling

Allergic rhinitis (AR) is an inflammatory airway disease (IAD) that is characterized by itching, nasal obstruction, and sneezing. AR is induced by Th-2 inflammatory responses such as those mediated by IgE and IL-4. This study aims to investigate the therapeutic effects of an herbal concoction, which is a combination of Cinnamomum cassia and Artemisa annua extracts (CIAR) against ovalbumin (OVA)-induced allergic rhinitis in a Balb/C mouse model. The effect of CIAR on the Th-2 mediated inflammatory response in the AR mouse model was studied by analyzing blood or nasal fluid samples. Experimental results revealed that OVA inhalation increased IgE, IL-4, IL-33, and TSLP levels, leading to Th2-type cytokine response. CIAR was found to significantly reduce the Th-2 response and levels of cytokines, including IL-4, IL-33, and thymic stromal lymphopoietin (TSLP). CIAR also down-regulated eosinophil (EOS) and basophil (BASO) levels in the blood. Histological analyses demonstrated decreased OVA-induced thickness of the respiratory epithelium in the CIAR-treated group. Collectively, our results suggest that the herbal concoction CIAR can effectively ameliorate the development of allergic rhinitis through the inhibition of Th-2 mediated responses.

Effect of Src tyrosine kinase on a rat model of asthma

Src tyrosine kinase is a protein encoded by the Src gene. The present study aimed to determine the role of Src protein kinase in asthma using small interfering RNA (siRNA) technology. Several Src siRNAs were designed and the most effective siRNA pair was selected. A rat model of asthma was established using ovalbumin, and the rats were treated with Src siRNA, empty vector or phosphate-buffered saline (PBS). A non-asthmatic control group was also established. The rats were clinically observed and Src mRNA and protein levels were measured by reverse transcription-quantitative PCR and western blot analysis, respectively. Pathological observation of the lung tissue, counting of white blood cells (WBCs) and eosinophils (EOSs) and analysis of the concentrations of IL-5, IL-33 and IFN-γ in the bronchoalveolar lavage fluid were performed. The expression levels of Src mRNA in the control, PBS, empty vector and siRNA groups were 110±30.7x103, 253±55.4x103, 254±41.3x103 and 180±50.9x103, respectively. Histochemical analysis of the lung tissue of rats in the siRNA group exhibited a relatively complete lung structure and little damage to the alveolar cavity. Src protein expression and IL-5, IL-33 levels, WBC and EOS levels were positively correlated with Src mRNA expression, while the IFN-γ concentration was negatively correlated with Src mRNA expression. These results indicate that Src knockdown inhibits the release of tracheal inflammatory factors and significantly alleviates asthma in rats. In conclusion, the present study utilized a gene transfer technique to interfere with the expression of Src in rats, which decreased the levels of IL-5, IL-33, WBCs and EOSs and increased the level of IFN-γ; these changes effectively ameliorated the condition of the trachea in asthmatic rats.

Evaluation of Haematological and Biochemical Activity of Thai Traditional Antinausea Remedy in Normal Albino rats

The present study was aimed to evaluate the effect of Thai Traditional anti-nausea remedy against haematological and biochemical effects in animals in the acute toxicity and sub-acute toxicity phase. Twenty-two male and female rats were divided into four groups with equal numbers of sex, each group were respectively received distilled water, 500, 1000 and 2000 mg/kg body weight as a single dose by gavage. While the experiment in the sub-acute phase, eighteen male and female rats were divided into three groups with equal numbers of sex. Each group were respectively given distilled water, 500 and 1000 mg/kg body weight once a day for the duration of the experiment until collecting blood samples. The blood samples were collected for haematological: Red Blood Cell (RBC), Haemoglobin (HGB), Hematocrit (HCT), Mean Corpuscular Volume (MCV), White Blood Cell (WBC), Neutrophil (NEU), Lymphocyte (LYMPH), Monocyte (MONO), Eosinophil (EO), Basophil (BASO) and biochemical analysis; Glucose (GLU), Blood Urea Nitrogen (BUN), Creatinine (CREA), Cholesterol (CHOL) and Triglyceride (TG). The results showed that the remedy caused behavioural adverse effects, but no mortality observed. In the acute toxicity phase, single oral administration of anti-nausea remedy increased mean difference compared to the control group on Creatinine level and decreased in AST level and ALP level (P&lt;0.05). In the subacute study, daily oral administration of the remedy did not result in death or changes in the body weight and food consumption but also showed comparable results on renal function marker including increasing of BUN levels and decreasing of AST level and ALP level (P&lt;0.05). In haematological and some biochemical analyses showed few disadvantageous effects. Based on the results obtained, although there were some changes in blood chemistry values, these were small changes not higher than reference values, indicating that the remedy was safe to take for a short period of time.

Effect of Allium sativum methanol extract in amelioration of arsenic-induced toxicity in Swiss albino mice

Background: Arsenic (As) toxicity is a major public health concern in many countries worldwide. Chronic arsenic toxicity results in multiple organ failure, cancer, neurological disorder, behavioral disorder, reproductive complications, etc. Allium sativum (garlic) has been reported to ameliorate mercury, lead, and cadmium-induced toxicity previously. Purpose: This research was aimed to evaluate the effect of methanol garlic extract in the amelioration of arsenic toxicity in Swiss albino mice. Methods: Initially 36 Swiss albino mice were divided into 6 different groups such as control group, arsenic-treated group where dose of arsenic was 0.0075 mg/mL, and arsenic plus methanolic extract of garlic treated group, and mice were treated at three different doses of extract; 150, 300, and 500 mg/kg for 8 weeks. Finally, the change in body weight, hematological, and biochemical parameters were measured. Results: Progressive body weight increase was observed in the control and only extracts treated groups whereas retardation of the body weight gain was found in the arsenic treated group. A decrease in the body weight gain was retarded in the groups that received arsenic plus garlic extract (GE). Compared to control, neutrophil (NEU), and eosinophil (EOS) counts as well as alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (CRE), and serum glutamic-pyruvic transaminase (SGPT) levels were increased whereas white blood cell (WBC), red blood cell (RBC), lymphocyte (LYM), and monocyte (MON) count were decreased in the arsenic-treated group. All these parameters were returned to normal levels in the garlic methanol extract-treated group. Conclusion: This study suggests that garlic has the potential for depleting arsenic-induced toxicity and thus, dietary intake of garlic might have therapeutic benefits in the prevention or amelioration of arsenic-exposed toxicity.

Особливості відповіді на базисну протизапальну терапію школярів з альтернативними запальними фенотипами бронхіальної астми

Purpose — to evaluate the effectiveness of long-term anti-inflammatory therapy with inhaled glucocorticosteroids in children with alternative inflammatory phenotypes of bronchial asthma (BA) for the development of individualized control treatment. Materials and methods. A comprehensive survey of 94 school-age children with BA was conducted. According to the results of cytological examination of sputum, 2 clinical observation groups were formed. The first group of patients was formed by 38 patients with non3eosinophilic (neutrophilic) nature of the inflammatory process of the bronchi (mean age — 11.1±2.9 years, the proportion of boys — 52.6±8.1%), and the second group — 56 children with eosinophilic type of airway inflammation (3% or more of eosinophilic granulocytes in sputum), ie eosinophilic asthma phenotype (mean age — 12.2±3.2 (P&gt;0.05) years, the proportion of boys — 67.9±6.2%, P&gt;0.05). According to the main characteristics of the observation group could be compared. All patients underwent a comprehensive clinical and paraclinical (spirographic) examination. Scoring control of BA symptoms was performed using a questionnaire at the beginning and at the end of the course of anti-inflammatory basic therapy. The questionnaire included the clinical signs of BA reflected in the scores, which were evaluated by patients and their parents, as well as the scale of instrumental studies according to the spirographic examination of patients. Results. The paper shows that the best effect of long-term courses of basic therapy with inhaled glucocorticosteroids (ICS) was observed in patients with eosinophilic airway inflammation. Thus, the share of patients with a relatively satisfactory level of clinical control of the disease and with close to normal spirographic indicators was in group II: before the course of treatment with inhaled corticosteroids 25.0% and 31.9%, and after treatment — 81.3% (P&lt;0,01) and 69.0% (P&lt;0.01), respectively. Thus, an increase of 69.3% in relative risk (IRR) and 56.3% in absolute risk (IAR) of BA control reflected a pronounced control effect of inhaled corticosteroids in the eosinophilic nature of airway inflammation. The minimum number of patients needed to treat (NNT) in order to obtain at least one positive result was 2. At the same time, in patients with neutrophilic inflammatory process, the proportion of patients with a relatively satisfactory level of clinical and paraclinical (according to spirography) disease control was: before the appointment of ICS — 30.8% and 30.8%, and after treatment — 50% (PFisher's exact test&gt;0.05) and 76.9% (PFisher's exact test&lt;0.01), respectively. This persistence of clinical manifestations of the disease indicated an insufficient level of control of non3eosinophilic BA in the treatment of inhaled corticosteroids and questioned the feasibility of monotherapy with this group of neutrophilic bronchitis. The insufficient effect of anti3inflammatory therapy with inhaled corticosteroids was evidenced by the fact that IRR of satisfactory level of clinical control was 38.4%, IAR — 19.2%, and NNT — 6 patients. Conclusions. In patients with the eosinophilic phenotype of BA, the use of long courses of inhaled glucocorticosteroids led to an increased chance of achieving disease control, while the chances of improving of the pulmonary function tests were also observed in the neutrophilic phenotype of the disease. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: bronchial asthma, children, basic anti-inflammatory therapy.

Microscopy suggests that glutathione S‐transferase is stored in large granules of myeloid cells in bone marrow and sparse granulocytes of the regenerating tail of lizard

AbstractMicroscopy suggests that glutathione S‐transferase is stored in large granules of myeloid cells in bone marrow and sparse granulocytes of the regenerating tail of lizard. Acta Zoologica (Stockolm). Tail regeneration in lizards occurs after an immune‐privileged blastema and is formed where various immunosuppressive cells and biomolecules keep inflammation low. Molecules that limit inflammation may include glutathione and glutathione S‐transferase (GST). These molecules reduce reactive oxidative species (ROS) and detoxify extraneous molecules. In the present study, the presence of GST has been analysed in the early phases of tail regeneration in the lizard Podarcis muralis. Using a rabbit polyclonal antibody directed against epitopes present in GST of P. muralis, a light and electron microscopy immunohistochemical and Western blotting study has been done. The study detected proteins of 25 and 32 kDa in pale‐medium electron‐dense and large granules present in promyelocytes and myelocytes of likely basophilic or eosinophilic fate that is present in the bone marrow of tail vertebrae. These cells are still proliferating and give rise to basophilic or eosinophilic granulocytes that also migrate into the regenerating tail. The enzyme stored in granules of promyelocytes and myelocytes is also localized in the cytoplasm of granulocytes present in the regenerating blastema‐cone, basophilic or/and eosinophilic. It is suggested that these granulocytes in the blastema reduce ROS and detoxify potentially inflammatory metabolites, contributing with other molecules to limit inflammation and favour regeneration.

Comprehensive characterization of central BCL-2 family members in aberrant eosinophils and their impact on therapeutic strategies

PurposeHypereosinophilia represents a heterogenous group of severe medical conditions characterized by elevated numbers of eosinophil granulocytes in peripheral blood, bone marrow or tissue. Treatment options for hypereosinophilia remain limited despite recent approaches including IL-5-targeted monoclonal antibodies and tyrosine kinase inhibitors.MethodsTo understand aberrant survival patterns and options for pharmacologic intervention, we characterized BCL-2-regulated apoptosis signaling by testing for BCL-2 family expression levels as well as pharmacologic inhibition using primary patient samples from diverse subtypes of hypereosinophilia (hypereosinophilic syndrome n = 18, chronic eosinophilic leukemia not otherwise specified n = 9, lymphocyte-variant hypereosinophilia n = 2, myeloproliferative neoplasm with eosinophilia n = 2, eosinophilic granulomatosis with polyangiitis n = 11, reactive eosinophilia n = 3).ResultsContrary to published literature, we found no difference in the levels of the lncRNA Morrbid and its target BIM. Yet, we identified a near complete loss of expression of pro-apoptotic PUMA as well as a reduction in anti-apoptotic BCL-2. Accordingly, BCL-2 inhibition using venetoclax failed to achieve cell death induction in eosinophil granulocytes and bone marrow mononuclear cells from patients with hypereosinophilia. In contrast, MCL1 inhibition using S63845 specifically decreased the viability of bone marrow progenitor cells in patients with hypereosinophilia. In patients diagnosed with Chronic Eosinophilic Leukemia (CEL-NOS) or Myeloid and Lymphatic Neoplasia with hypereosinophilia (MLN-Eo) repression of survival was specifically powerful.ConclusionOur study shows that MCL1 inhibition might be a promising therapeutic option for hypereosinophilia patients specifically for CEL-NOS and MLN-Eo.

Duodenal mast cells and eosinophils in children with celiac disease: occurrence and distribution pattern

Objective The aim of this study was to characterize duodenal mast cell (MC) and eosinophil (EO) numbers, their distribution within the lamina propria and possible impact on disease severity of paediatric celiac patients compared to children without celiac disease (CD). Methods We analysed duodenal samples of 215 children (109 CD, 106 controls) who underwent esophagogastroduodenoscopy from 2010 to 2018. After immunohistochemical staining, average MC and EO counts were histologically examined in ten high-power-fields. Additionally, cell-distribution within the lamina propria was analysed. Possible influence of relevant clinical parameters was evaluated. Statistics Student’s-t-test, Mann–Whitney U-test, Chi-square-test, ANOVA, significance-level <.05. Trial registration-number: DRKS00024669. Results MC-density was higher in CD-patients compared to the control-group (23.7 (±12.1)/HPF versus 19.7 (±9.1)/HPF; p = .008), varying in number interindividually. Eosinophils were also increased in the duodenum of celiac patients (23.3 (±9.3)/HPF versus 12.2 (±6.3)/HPF; p= <.001). MCs were distributed more often homogenously in all parts of CD lamina propria (44 biopsies (40.4%), residing more distant from the intestinal lumen in controls (0 biopsies with homogenous distribution-pattern (0%); p= <.001). Regarding EOs no polarity was observable. Atopic diseases did not occur significantly more often in patients with elevated EO-counts. Conclusion MC- and EO-numbers were increased in the duodenum of CD-patients and MCs showed a different distribution-pattern in the lamina propria of celiac patients. These findings support the concept that both cell-types contribute to disease-pathogenesis. However, functional studies highlighting both cell-types’ and their mediators’ role regarding mucosal alterations during the course of the inflammatory process in celiac patients are needed. Trial registration number and URL DRKS00024669; https://www.drks.de/drks_web/

The relationship between clinical pathology and prognosis of chronic rhinosinusitis

Objective:To explore the pathological type, clinical features and their relationship with prognosis of chronic rhinosinusitis（CRS）. Methods:A retrospective study of 135 patients with CRS who underwent surgical treatment in the Affiliated Jiangning Hospital of Nanjing Medical University from January 2017 to December 2018. Review the pathological slices retrospectively and divide the CRS into 4 types, eosinophilic type（eCRS）, lymphocyte or（and） plasma cell type, neutrophil type and mixed type, the latter three are collectively referred to as "non-eosinophil type（non-eCRS）". Follow-up was conducted between January and February 2021 to analyze the distribution, clinical features, and differences in prognosis of the different endotypes. Results:①Among the 135 CRS patients, 42 cases（31.1%） were eCRS and 93 cases（68.9%） were non-eCRS（76 cases[56.3%] of lymphocyte or plasma cell type, 4 cases[3.0%] of neutrophil type and 13 cases[9.6%] of mixed type）. The difference in composition ratio between the groups was statistically significant（n=135, P<0.001）. ②The absolute value and percentage of preoperative peripheral blood eosinophils（EOS） in eCRS patients were higher than those of non-eCRS patients, and the difference was statistically significant（n=125, P（absolute value）=0.030, P（percentage）=0.033）. The results of receiver operating characteristic curve showed that both absolute value and percentage have predictive value, and cut-off value was 0.325×10⁹/L（absolute value） or 2.750%（percentage）. There was no statistically significant difference in preoperative peripheral blood procalcitonin among the groups（n=69, P=0.647）. ③The ratio（E/M value） of the bilateral ethmoid sinus scores and bilateral maxillary sinus scores of the preoperative paranasal sinus CT in eCRS patients was 2.03±1.23, while the non-eCRS patients was 1.47±0.96, and the difference was statistically significant（n=112, P=0.009）. ④In total, 101 cases were effectively followed up, including 34 cases of eCRS（7 cases[20.6%] of control, 18 cases[52.9%] of partial control）, 9 cases[26.5%] of non-control and 67 cases of non-eCRS（32 cases[47.8%] of control, 26 cases[38.8%] were partially controlled, 9 cases[13.4%] were not controlled）, and the efficacy of the non-eCRS group was significantly better than that of the eCRS group（χ²=7.499, P=0.024）. Conclusion:When the absolute value of EOS in the preoperative blood examination is greater than 0.325×10⁹/L or the percentage is greater than 2.750%, eCRS can be predicted, but the accuracy is low. CT of patients with eCRS is mostly characterized by inflammation of the ethmoid sinus and usually E/M>2. The efficacy of eCRS group is worse than that of the non-eCRS group 2-4 years after surgery.

Integrated analysis of blood mRNAs and microRNAs reveals immune changes with age in the Yangtze finless porpoise (Neophocaena asiaeorientalis).

Populations of Yangtze finless porpoises (YFPs) have rapidly declined in recent decades, raising the specter of extinction. In order to protect YFPs, a greater understanding of their biology is needed, including studying how their immune functioning changes with age. Here, we systematically studied the hematologic and biochemical parameters, as well as mRNAs and miRNAs profiles of old, adult, and young YFPs. The lymphocyte (LYMPH), neutrophils (NEUT) and eosinophils (EOS) counts in old YFPs were lower than those in young or adult YFPs. When comparing old to adult YFPs, the latter showed higher expression of genes associated with the innate and adaptive immune systems, including complement components, major histocompatibility complex, interleukins, TNF receptors, and chemokines/cytokines. When comparing old to young YFPs, the most striking difference was in higher toll-like receptor signaling in the latter. When comparing adult to young YFPs, the former exhibited higher expression of genes related to adaptive immunity and the FoxO signaling pathway, but lower expression of genes associated with the PI3K-Akt signaling pathway. Negative miRNA-mRNA interactions were predicted in comparisons of the old and adult (326), old and young (316), adult and young (211) groups. Overall, these results delineate a progression from early innate immune function dominance to adaptive immune function enhancement (young to adult) and deterioration (adult to old), and the changes in miRNAs profile correlate with the effects of age on immune functions. This study is the first to observe the changes of immune function of Yangtze finless porpoise with age using transcriptome method, and the study's findings are of great significance for protecting this endangered species.

Clinical Analysis of Dispelling Wind, Eliminating Lung and Relieving Cough Combined with Western Medicine in the Treatment of Cough Variant Asthma in Children

Objective: This study mainly explores the clinical effect of dispelling wind, eliminating lung and relieving cough combined with western medicine in the treatment of cough variant asthma. Methods: 80 children with cough variant asthma accepted by our hospital from January 2018 to December 2020 were randomly selected for the study and divided into two groups. One group was the reference group (40 cases) treated with procaterol hydrochloride tablets and montelukast sodium, and the other group was the research group (40 cases). The method of eliminating wind, eliminating lung and relieving cough was combined with procaterol hydrochloride tablets and montelukast sodium to observe and compare the curative effects of the two groups. Results: There was no significant difference in TCM symptom score and eosinophil (EOS) count between the two groups before treatment (P &gt; 0.05); After treatment, the TCM symptom scores of coughs, pharyngeal itching, expectoration, nasal congestion and nasal itching in the research group were lower than those in the reference group, and the EOS count was lower than that in the reference group (P &lt; 0.05); The effective rate of research group was higher than that of reference group (P &lt; 0.05). Conclusions: For children with cough variant asthma, Qufeng Sufei cough relieving method combined with procaterol hydrochloride and montelukast sodium can improve children’s symptoms and reduce eosinophil count.