ECP Levels Research Articles

Noninvasive Disease Assessment in Eosinophilic Esophagitis With Fractionated Exhaled Nitric Oxide, Blood, and Fecal Biomarkers.

Eosinophilic Esophagitis (EoE) is a chronic inflammatory condition of the esophagus triggered by food and aeroallergens. There is a need for noninvasive biomarkers that reliably detect EoE in patients with cardinal symptoms and predict treatment response to reduce endoscopic evaluations. Nonasthmatic patients 18 years or above with suspected or diagnosed EoE, gastroesophageal reflux disease (GERD), and control individuals with indication for endoscopy were enrolled prospectively between November 2020 and May 2022. Participants underwent body plethysmography with fractionated exhaled nitric oxide (FeNO) level measurement. Besides, serum and fecal biomarkers were measured by ELISA. A follow-up examination was scheduled after treatment initiation in patients with active EoE. The median FeNO level in active EoE (20 ppb) was higher compared with GERD (15 ppb, P=0.038) and control individuals (14 ppb, P=0.046). Median FeNO did not significantly differ in EoE patients who underwent follow-up assessment after treatment response (20 ppb vs. 18 ppb, P=0.771). Serum EDN, ECP, and the absolute eosinophil blood count (AEC) were elevated in active EoE compared with control individuals but not compared with GERD except for AEC. Serum EDN, ECP and AEC decreased in EoE in remission at follow-up assessment. None of the fecal biomarkers was elevated in active EoE or during treatment. Assessment of FeNO may have diagnostic value in differentiating patients with active EoE from non-EoE patients but is not a suitable marker for monitoring disease activity. Serum EDN, ECP, TARC, and AEC levels are emerging as potential candidates for monitoring disease activity in EoE.

Inhibition of dendritic cell autophagy alleviates the progression of allergic rhinitis by inhibiting Th1/Th2/Th17 immune imbalance and inflammation.

Immune imbalance is a fundamental immunological feature of allergic rhinitis (AR). The autophagy in CD11c+ dendritic cells (DCs), the strongest antigen-presenting cells, was reported to induce the occurrence of AR by facilitating CD4+ T cell immune imbalance and subsequent inflammation. Our study was designed to confirm that inhibition of DC autophagy can alleviate the progression of AR by inhibiting the T cell immune imbalance. The AR mouse model was established by using ovalbumin (OVA). OVA-induced mouse models were then injected intraperitoneally with the autophagy inhibitor Baf-A1. Levels of OVA-specific IgE, PGD2, ECP, LTC4, and Th1/Th2/Th17 cell-related cytokines in serum or nasal lavage fluid (NLF) were examined using the corresponding commercial ELISA kits. Morphological changes in the nasal mucosa were observed by HE staining. Nasal mucosa tissues were collected for western blotting to assess the expression of autophagy markers (LC3, P62, and Beclin 1) in each group of mice. Baf-A1 treatment alleviated the allergic symptoms, mitigated inflammatory immune cell infiltration in the nasal mucosa, decreased IgE, LTC4, ECP, and PGD2 levels in both serum and NLF, impaired CD11c+ DC autophagy, and restored Th1/Th2/Th17 cytokine imbalance in OVA-induced AR mice. Furthermore, Baf-A1 treatment also reversed the immune imbalance of CD4+ T cell subtypes and attenuated Th1/Th2/Th17 cytokine imbalance in vitro. Inhibition of CD11c+ DC autophagy suppressed the immune imbalance of CD4+ T cell subsets and attenuated the subsequent inflammatory response, thereby ameliorating the progression of AR.

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease. To identify proteins in the circulation associated with HDPs. Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023. Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs). Gestational hypertension and preeclampsia. Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins. Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.

IL-13 and IL-13–induced periostin levels are specifically decreased in patients following endoscopic sinus surgery for chronic rhinosinusitis

BackgroundType 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS) effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown. ObjectiveTo compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing CRS from non-CRS patients, identifying major phenotypes (CRS without (CRSsNP) and with nasal polyps (CRSwNP)), assessing endotypic change and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS. MethodsMM mucus samples were collected from CRSsNP and CRSwNP patients before and 6-12 months after ESS and compared to non-CRS control patients. T2 biomarkers were evaluated continuously, using threshold-based definitions of T2 endotype, and for relationships with patient-reported (SNOT-22 and CRS-PRO) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels. Results154 CRS patients (89 CRSsNP, 65 CRSwNP) were enrolled with a mean 9-month interval between ESS and follow-up. Pre-ESS MM mucus analysis revealed elevated T2 mediators in CRSwNP vs. CRSsNP and non-CRS controls. Temporally stable correlations between IL-13 and IL-5; periostin and C5a; and ECP and CCL26 was observed. On this basis and pathologic significance, IL-13, periostin and ECP were further analyzed. Post-ESS, IL-13 and periostin levels decreased significantly, ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP was higher in patients undergoing extensive surgery. ConclusionESS decreased IL-13 and periostin in MM. T2 inflammation post-ESS correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes.

Evaluation of autophagy inhibition to combat cancer: (vanadium complex)-protein interactions, parameterization, and validation of a new force field.

Autophagy has drawn attention from the scientific community, mainly because of its significant advantages over chemotherapeutic processes. One of these advantages is its direct action on cancer cells, avoiding possible side effects, unlike chemotherapy, which reaches tumor cells and affects healthy cells in the body, leading to a great loss in the quality of life of patients. In this way, it is known that vanadium complex (VC) [VO(oda)(phen)] has proven inhibition effect on autophagy process in pancreatic cancer cells. Keeping that in mind, molecular dynamics (MD) simulations can be considered excellent strategies to investigate the interaction of metal complexes and their biological targets. However, simulations of this type are strongly dependent on the appropriate choice of force field (FF). Therefore, this work proposes the development of AMBER FF parameters for VC, having a minimum energy structure as a starting point, obtained through DFT calculations with B3LYP/def2-TZVP level of theory plus ECP for the vanadium atom. An MD simulation in vacuum was performed to validate the developed FF. From the structural analyses, satisfying values of VC bond lengths and angles were obtained, where a good agreement with the experimental data and the quantum reference was found. The RMSD analysis showed an average of only 0.3%. Finally, we performed docking and MD (120 ns) simulations with explicit solvent between VC and PI3K. Overall, our findings encourage new parameterizations of metal complexes with significant biological applications, as well as allow to contribute to the elucidation of the complex process of autophagy.

Sputum inflammatory, neural, and remodeling mediators in eosinophilic and noneosinophilic asthma

BackgroundNeural and remodeling mechanisms may play a role in asthma, particularly noneosinophilic asthma (NEA). ObjectiveTo assess sputum mediators associated with neural, remodeling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and participants without asthma. MethodsA total of 111 participants with and 62 without asthma (14-21 years old) underwent sputum induction, exhaled nitric oxide, atopy, and spirometry tests. There were 24 mediators measured in sputum using enzyme-linked immunosorbent assay or bead array. Eosinophilic asthma (n = 52) and NEA (n = 59) were defined using a sputum eosinophil level cut-point of greater than or equal to 2.5%. ResultsElevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, P = .03), periostin (33.8 vs 9.4 ng/mL, P = .01), and ECP; (220.1 vs 83.7 ng/mL, P = .03) were found in patients with asthma compared with those without asthma. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, P = .02) compared with participants without asthma. Eosinophilic asthma had higher levels of inflammatory mediators (ECP: 495.5 vs 100.3 ng/mL, P ≤ .01; interleukin-1β: 285.3 vs 209.3 pg/mL, P = .03; histamine: 5805.0 vs 3172.5 pg/mL, P < .01) and remodeling mediators (VEGF-A); 3.3 vs 2.5 ng/mL, P = .03; periostin: 47.7 vs 22.1 ng/mL, P = .04) than NEA. Whereas macrophages were associated with neural mediators, for example, neurokinin A (r = 0.27, P = .01) and nociceptin (r = 0.30, P = .02), granulocytes were associated with inflammatory and remodeling mediators (eg, ECP and VEGF-A correlated with neutrophils (r = 0.53 and r = 0.33, respectively, P < .01) and eosinophils (r = 0.53 and r = 0.29 respectively, P ≤ .01). ConclusionElevated levels of nociceptin and inflammatory and remodeling markers were found in EA, but no evidence for neural and remodeling pathways was found in NEA. Neural and remodeling mechanisms seem to coexist with inflammation.

Ring Strain Energies of Three-Membered Homoatomic Inorganic Rings El3 and Diheterotetreliranes El2Tt (Tt = C, Si, Ge): Accurate versus Additive Approaches.

Accurate ring strain energies (RSEs) for three-membered symmetric inorganic rings El3 and organic dihetero-monocycles El2C and their silicon El2Si and germanium El2Ge analogues have been computed for group 14–16 “El” heteroatoms using appropriate homodesmotic reactions and calculated at the DLPNO-CCSD-(T)/def2-TZVPP//B3LYP-D4/def2-TZVP(ecp) level. Rings containing triels and Sn/Pb heteroatoms are studied as exceptions to the RSE calculation as they either do not constitute genuine rings or cannot use the general homodesmotic reaction scheme due to uncompensated interactions. Some remarkable concepts already related to the RSE such as aromaticity or strain relaxation by increasing the s-character in the lone pair (LP) of the group 15–16 elements are analyzed extensively. An appealing alternative procedure for the rapid estimation of RSEs using additive rules, based on contributions of ring atoms or endocyclic bonds, is disclosed.

Study of immunological parameter (ECP) of entamoeba gingivalis in immunocompromised patients with periodontitis in Al-Najaf Al-Ashraf City

Objectives: The present study aimed to compare the presence of E. gingivalis in immunocompromised patients with periodontitis and conrol group by measuring immunological parameter (ECP) by using ELISA. Methadology: A Comparison case-control study design was done on 80 samples [40 case ( 20 immunocompromised patients with peridontitis + 20 immunocompromised patients without peridontitis) were selected from Al-Sader Medical City/Middle Euphrates Cancer Center and 40 control (Diabetes Mellitus patients with poor oral sanitation)] were selected from AL-Najaf Center for Diabetes and Endocrinology/Al-Sadr Medical City, during the period from the beginning of November 2021 to the end of February 2022. Age range of cases and control between (20 - ≥ 60) years. Results: The results of the Salivery Tests (Immunological Cytokines Assays) showed the concentration levels of ECP was (6.6860 ± 2.97386Pg/ml) in immunocompromised patients with Periodontitis. But in immunocompromised patients without Periodontitis was (4.7280 ± 3.46401 Pg/ml). While in control group (Diabetic Mellitus Poor Oral Sanitation) was (49.294 ± 22.42156 Pg/ml). Conclusion: The infection rate of the E.gingivalis parasite in the control group (Diabetic Mellitus Poor Oral Sanitation) was twice higher than that of the immunocompromised patients with peridontitis and without peridontitis.

Effect of Bairui Granule on Inflammatory Mediators in Induced Sputum, Leukotriene C4, and EOS in Peripheral Blood of Children with Cough Variant Asthma.

Objective To study the effect of Hanchuan Zupa granule combined with conventional western medicine in the treatment of children with bronchial asthma. Methods 98 cases in Fengrun District People's Hospital of Tangshan City from June 2018 to February 2021 were selected. The control group was given oxygen therapy, antibiotics, and aerosol inhalation of quick acting β 2 receptor agonist, glucocorticoid, and other conventional western medicine treatment, while the observation group was treated with Bairui granule on the basis of the control group. The course of treatment of the two groups was 1 week. Results After treatment, the levels of sputum IL-4, IL-17, neu, and ECP in the two groups decreased, and the observation group was lower than the control group (P < 0.05). The levels of EOS, CXCR4, LTB4, and SDF-1 in peripheral blood of the two groups were lower than those in the control group (P < 0.05). The daytime cough, night cough, and TCM syndrome scores of the two groups were decreased, and the observation group was lower than the control group (P < 0.05). Conclusion Bairui granule combined with conventional western medicine in the treatment of children with bronchial asthma, the curative effect is worthy of affirmation, can effectively improve cough symptoms, reduce EOS, CXCR, LTB4, SDF-1 levels, inhibit airway inflammation, and has good clinical application value.

Assessing the role of eosinophil-mediated immune response markers in detecting hookworm infection: A case-control study in Kintampo, Ghana.

Background and AimHuman hookworm disease caused by Ancylostoma duodenale and Necator americanus is a serious public health problem. Hookworm infection activates eosinophil‐mediated tissue inflammatory responses, involving the production of the eosinophil‐specific chemokine (eotaxin), recruitment of eosinophils, secretion of the cationic protein, and production of antiparasite immunoglobulin E (IgE). We investigated eosinophil‐mediated immune response as markers (CCL11, eosinophil cationic protein [ECP], and IgE) for detecting hookworm infection.MethodsThis case‐control study was carried out in hookworm endemic areas within the Kintampo North Municipality.Forty hookworm‐positive subjects and 36 apparently healthy individuals were recruited as cases and controls, respectively. Stool samples were collected for hookworm detection by the Kato–Katz technique and speciation by polymerase chain reaction. Approximately, 5 ml of intravenous blood was used to obtain plasma for the immunological assays.ResultsOf eosinophil‐mediated immune response markers studied, ECP and CCL11 were significantly higher among hookworm patients compared to controls. Increasing CCL11 (β = −0.81, p = 0.015) was associated with a significant decrease hookworm intensity. However, increasing eosinophil count (β = 0.62, p = 0.027) was associated with significant increase in hookworm intensity. In receiver operator characteristics analysis, ECP could significantly detect hookworm infection with a very high area under the curve (AUC) (AUC = 0.97, p < 0.0001). At a cutoff of 39.05, ECP was the best eosinophil‐mediated immune response marker for detecting hookworm infection with a sensitivity of 97.2%, specificity of 87.8%, a positive predictive value of 89.7%, and a negative predictive value of 96.6%.ConclusionECP best predicts eosinophil‐mediated immune response for detecting hookworm infection, while CCL11 and eosinophil count better predict the intensity of hookworm. Moreover, the ECP level is a good indicator of hookworm infection and intensity and may require additional investigations to augment current hookworm diagnostic techniques.

Accurate Ring Strain Energies of Unsaturated Three-Membered Heterocycles with One Group 13-16 Element.

High-quality ring strain energy (RSE) data for 1H-unsaturated (CH)2X parent rings, where X is a group 13–16 element, are reported in addition to the 2H-isomers of the pnictogenirene rings. RSE data are obtained from appropriate homosdesmotic reactions and calculated at the DLPNO-CCSD(T)/def2-TZVPP//B3LYP-D3/def2-TZVP(ecp) level. 1H-Tallirene and 1H-plumbirene have unique donor–acceptor structures between an acetylene π(CC) orbital and an empty p orbital of a metallylene subunit (a Dewar–Chatt–Duncanson description) and therefore cannot be described as proper rings but as pseudocyclic structures. Also, 1H-indirene and 1H-oxirene lack ring critical points and constitute borderline cases of pseudorings. 1H-Unsaturated rings exhibit enhanced RSE compared to their saturated homologues. The mechanism of ring strain relaxation by increasing the s character in the lone pair (LP) of group 15–16 elements is remarkable and increases on descending the groups. Furthermore, RSE is affected by the aromatic character of group 13 rings and certain aromatic or antiaromatic character in group 14 or 15–16 rings, respectively, which tend to vanish on descending the group as shown by NICS(1) values. 2H-Unsaturated rings were found only for group 15 elements (although only 2H-azirine shows a proper cyclic structure) and displayed lower RSE (higher stability) than the corresponding 1H-isomers.

Roles Played by the PI3K/Akt/HIF-1α Pathway and IL-17A in the Chinese Subtype of Chronic Sinusitis with Nasal Polyps.

Background The Chinese subtype of CRSwNP may have a unique pathogenesis. This study was designed to seek the role of the PI3K/Akt/HIF-1α pathway and IL-17A in CRSwNP. Methods The total IgE, ECP, and IL-17A levels were determined by UniCAP100 and ELISA. The activity of MPO was detected by the biochemical techniques. The protein expressions of HIF-1α, p-Akt, and PI3K were detected by the WB method. HIF-1α and IL-17A mRNA levels were measured by RT-PCR. Results The CRSwNP group showed significantly elevated MPO activity, PI3K, p-AKT protein, HIF-1α, and IL-17A mRNA levels in nasal polyps. Stimulated by the TNF-α, the PI3K, p-AKT, HIF-1α, and IL-17A levels significantly elevated in the fibroblasts. Inhibited by the Wortmannin, those indicators significantly declined in the fibroblasts. Conclusion The PI3K/Akt/HIF-1α pathway played a role in the pathogenesis of CRSwNP. The elevated IL-17A level might be responsible for the neutrophilic inflammation in CRSwNP. The PI3K/Akt/HIF-1α pathway might regulate the IL-17A-related inflammation in CRSwNP.

EOSINOPHIL CATIONIC PROTEIN AND IRON STATUS IN PATIENTS INFECTED WITH Enterobius vermicularis

The primary goal of this study was to determine the function of eosinophil cationic protein in iron status in patients infected with Enterobius vermicularis. For this, a total of 583 suspected patients and thirty healthy people of the same age who have visited the AL-Zahra maternity and pediatrics laboratory, AL-Hakeem hospital, AL-Sajad hospital AL-Fruit al-Awsat hospital, and AL-Munadira hospital in AL-Najaf province from July 2020 to June 2021 were screened. The presence of E. vermicularis eggs was estimated by using the saline wet mount technique from faeces samples of all respondents. Blood samples were collected from the 60 positive and 30 healthy control group and centrifuged at 3000 rpm for 5 minutes to separate serum, which was then collected in sterile tubes. Each serum sample was divided into three parts and stored in the deep freezer at -20°C until the serological test was performed. The level of ECP, iron and ferritin in enterobiasis patients was estimated from the isolated blood serum. According to the Manufacturer Company instructions, the concentration of two biomarkers (ECP, Ferritin) in serum samples was determined using the ELISA technique (Human reader, Germany). While the concentration of iron was evaluated using a colourimetric method. In comparison to the control group, the concentration of ECP was reported significantly higher (P&lt;0.05) in the E. vermiculris infected patients while the concentration of serum iron and ferritin was significantly decreased. The results of the current study can be concluded that E. vermicularis infection changes the serum ECP, iron, and ferritin concentration.

The role of Staphylococcus aureus in the course of polyposis sinusitis

Introduction. Today, there are lot of theories of pathogenesis of polypoid sinusitis. The contribution of Starchylocossus aureus (S. aureus) to the occurrence of this pathogenetic reaction is being actively discussed.Objective: to improve the effectiveness of treatment of polypoid sinusitis using the results of the study of the effect of persistent staphylococcal infection on the onset and course of the disease.Materials and methods. The authors examined 105 patients with recurrent polyposis sinusitis aged 20 to 65 years. All patients underwent FESS surgery for recurrent polypous sinusitis at the initial visit. In the postoperative period, all patients received treatment according to one of two schemes. The first scheme included antihistamines and topical steroids, the second additionally included clarithromycin. The patients underwent bacteriological examination of smears for flora and fungi from the cavity; cytological examination of smears-prints from the mucous membrane of the nasal cavity (we counted neutrophils, eosinophils and lymphocytes in the preparation); immunological and allergic examination (skin tests, serum specific IgE levels).Results and discussion. It has been established that the presence of a carriage and sensitization to S. aureus in a patient, especially in combination with atopy, results in a more severe course of polyposis sinusitis severe nasal obstruction (91% versus 69.5%, respectively) and is characterized by more pronounced eosinophilic inflammation than Polypoid Sinusitis associated with infection with other microorganisms (the number of eosinophils in the blood: 7.5% and 4.3%, respectively; the level of eosinophils in smears from the nasal mucosa is 13 and 4.8%, respectively; the average ECP level is 17.6 and 8.1 ug / ml, respectively).Conclusions. The use of topical GCS remains one of the leading methods for preventing recurrence of PS. However, in addition to the backbone therapy with topical GCS and antihistamines, it is advisable to complete a course of antibiotics during nasal colonization with S. aureus.

Perfectionistic tipping points: Re-probing interactive effects of perfectionism.

Researchers have recently turned their attention to examining interactive effects of dimensions of perfectionism in sport and exercise. This is typified by research testing the 2 × 2 model of perfectionism (Gaudreau & Thompson, 2010) and the use of simple slopes analysis to probe statistically significant interactions. The aim of this study is to illustrate a different approach to probe statistically significant interactions, the Johnson-Neyman (J-N) technique, and how it can identify the specific level of evaluative concerns perfectionism at which the effect of personal standards perfectionism changes (termed the perfectionistic tipping point). To meet this aim, secondary analysis was undertaken of three samples that previously provided evidence of interactions between dimensions of perfectionism in predicting sport devaluation, dedication, enthusiasm, and expressive suppression. Using the J-N technique, perfectionistic tipping points were identified whereby the conditional effect of PSP became statistically significant for each outcome at low-to-moderate levels of ECP. In each case, the level of ECP was outside of the levels tested in the 2 × 2 model making it useful complementary information. Based on the findings, it is recommended that researchers report perfectionistic tipping points when probing significant interactions in the 2 × 2 model of perfectionism and when examining interactive effects of perfectionism, generally.

A preliminary study on the biomarkers of local inflammation in allergic rhinitis

Objective:This study aimed to explore the biomarkers in nasal secretion that can assist in the diagnosis of allergic rhinitis（AR） and can be used to evaluate the therapeutic effect of AR. Methods:Thirty-three patients with AR and 21 healthy controls were included. The nasal secretion of healthy controls and patients with AR（before and after treatment） were collected. The cytology, the concentrations of cytokines（IL-5, IL-6, IL-8, IL-33, IFN-γ） and inflammatory mediators（ECP, MPO） were detected. Then, we compared the differences of various biomarkers between healthy controls and AR patients（before and after treatment group）. And analyzed the correlation between each biomarkers/biomarkers difference value/the percentage of biomarkers difference value and clinical symptom score/ score difference value / the percentage of score difference value. Results:Compared with normal controls, the levels of ECP, IL-5, IL-6, IL-8, IL-33 and IFN-γ in nasal secretion of AR patients were significantly higher than those of normal controls（P<0.05）. There was no significant difference in MPO. After treatment, ECP decreased significantly（P<0.01）, inflammatory cell grade and eosinophil percentage are also decreased（P<0.01）. However, MPO, IL-5, IL-6, IL-8, IL-33 and IFN-γ did not change significantly. The difference value of ECP before and after treatment was correlated with the difference value of VAS score（r=0.348, P=0.047）. The difference value of IL-5 was correlated with the difference value of VAS score and rhinorrhea, the correlation coefficients were 0.406（P=0.019） and 0.429（P=0.013）, respectively. The difference value of eosinophil percentage in nasal secretion before and after treatment was correlated with nasal congestion, and the correlation coefficient was 0.383. The difference value of eosinophil percentage multiplied by inflammatory cell grade before and after treatment was correlated with VAS score（r=0.417, P=0.016） and nasal congestion difference value（r=0.519, P=0.002）. The percentage of difference value of IFN-γ before and after treatment was correlated with the percentage of difference value of VAS score / rhinorrhea / sneeze / total nasal symptom score. Conclusion:ECP, IL-6, IL-8 and IL-33 in nasal secretion are expected to be objective biomarkers for auxiliary diagnosis of AR. And ECP, IL-5, IFN-γ, eosinophil percentage multiplied by grade is expected to be an objective index to judge the improvement of patients' symptoms after treatment.

Exploring the structural stability order and electronic properties of transition metal M@Ge12 (M = Co, Pd, Tc, and Zr) doped germanium cage clusters–A density functional simulation

In the present report, the structural stability order and electronic properties of the transition metal M@Ge12 (M = Co, Pd, Tc, and Zr) doped germanium cage has been carried out at B3LYP/LANL2DZ ECP level by using spin polarized density functional theory. Initially, we selected five lowest energy structure of neutral TM doped Ge12 cluster with high symmetry point like D6h-symmetric hexagonal prism (HP), the D6d-symmetric hexagonal anti-prism (HAP), D2d-symmetric bi-capped pentagonal prism (BPP), perfect icosahedrons (Ih) and Fullerene type structures. Further, we discussed the electronic origin of stability as well as electronic properties by calculating binding energy, HOMO-LUMO gap, charge transfer mechanism and density of states. We indentified that the Pd, Tc, and Zr encapsulated Ge12 cage with hexagonal prism [HP] structures are minimum energy structures while Co@Ge12 cage prefer HAP structure. The magnitudes of binding energy of the clusters indicate that the doping of 4d transition metal gives most stable structure rather than 3d transition metal Co atom. The large HOMO-LUMO gap and natural bond orbital analysis explain the stability of these clusters using closed shell electronic configuration and the contribution of π and σ bond. Charge transfer mechanism shows that the Tc, Pd and Zr atoms play role as an electron donor in the system whereas Co inclined to accept the electrons. The importances of “d” orbital in localized electrons near the Fermi level are also explained through partial density of states.

Elevated Levels of Activated and Pathogenic Eosinophils Characterize Moderate-Severe House Dust Mite Allergic Rhinitis.

Eosinophils play a critical role in the pathogenesis of allergic airway inflammation. However, the relative importance of eosinophil activation and pathogenicity in driving the progression of disease severity of allergic rhinitis (AR) remains to be defined. We aimed to assess the relation of activated and pathogenic eosinophils with disease severity of patients with AR. Peripheral blood and nasal samples were collected from patients with mild (n = 10) and moderate-severe (n = 21) house dust mite AR and healthy control subjects (n = 10) recruited prospectively. Expressions of activation and pathogenic markers on eosinophils in the blood and nose were analyzed by flow cytometry. The eosinophilic cation protein- (ECP-) releasing potential and the pro-Th2 function of blood eosinophils were compared between the mild and moderate-severe patients and healthy controls. Our results showed that the numbers of activated (CD44+ and CD69+) and pathogenic (CD101+CD274+) eosinophils in the blood and nose as well as blood eosinophil progenitors were increased in moderate-severe AR compared with the mild patients and healthy controls. In addition, the levels of activated and pathogenic eosinophils in the blood were positively correlated with the total nasal symptom score and serum ECP and eosinophil peroxidase (EPX) levels in patients with AR. Furthermore, the blood eosinophils obtained from the moderate-severe patients exhibited a higher potential of releasing ECP and EPX induced by CCL11 and of promoting Th2 responses than those from the mild patients and healthy controls. In conclusion, patients with moderate-severe AR are characterized by elevated levels of activated and pathogenic eosinophils, which are associated with higher production of ECP, EPX, and IL-4 in the peripheral blood.

Clinical value of IL-13 and ECP in the serum and sputum of eosinophilic AECOPD patients.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an inevitable trend in the development of the disease and eosinophils (EOS) participate in inflammation process. It is important to explore some relatively simple biomarkers in AECOPD which are useful to recognize the disease. In the present study, 108 hospitalized patients with AECOPD were collected and the levels of IL-13 and ECP in the serum and sputum were measured. The levels of IL-13 and ECP in sputum in the eosinophilic group were higher than those in the noneosinophilic group. Moreover, the noneosinophilic group had a higher rate of rehospitalization due to acute exacerbation during the one-year follow-up. The results show that eosinophils in peripheral blood are a simple, convenient, and inexpensive index for assessing the condition and prognosis of AECOPD patients. IL-13 and ECP are involved in the pathogenesis of eosinophilic AECOPD and may be the new targeted anti-inflammatory therapies.

Mitochondrial Functions, Energy Metabolism and Protein Glycosylation are Interconnected Processes Mediating Resistance to Bortezomib in Multiple Myeloma Cells.

The proteasome inhibitor bortezomib (BTZ) has emerged as an effective drug for the treatment of multiple myeloma even though many patients relapse from BTZ therapy. The present study investigated the metabolic pathways underlying the acquisition of bortezomib resistance in multiple myeloma. We used two different clones of multiple myeloma cell lines exhibiting different sensitivities to BTZ (U266 and U266-R) and compared them in terms of metabolic profile, mitochondrial fitness and redox balance homeostasis capacity. Our results showed that the BTZ-resistant clone (U266-R) presented increased glycosylated UDP-derivatives when compared to BTZ-sensitive cells (U266), thus also suggesting higher activities of the hexosamine biosynthetic pathway (HBP), regulating not only protein O- and N-glycosylation but also mitochondrial functions. Notably, U266-R displayed increased mitochondrial biogenesis and mitochondrial dynamics associated with stronger antioxidant defenses. Furthermore, U266-R maintained a significantly higher concentration of substrates for protein glycosylation when compared to U266, particularly for UDP-GlcNac, thus further suggesting the importance of glycosylation in the BTZ pharmacological response. Moreover, BTZ-treated U266-R showed significantly higher ATP/ADP ratios and levels of ECP and also exhibited increased mitochondrial fitness and antioxidant response. In conclusions, our findings suggest that the HBP may play a major role in mitochondrial fitness, driving BTZ resistance in multiple myeloma and thus representing a possible target for new drug development for BTZ-resistant patients.