ABSTRACT
Tropomyosin was reported as an important allergen in Crassostrea angulata and designated as Cra a 1. The localization of the T cell epitopes and the reduction of the immunoreactivity of Cra a 1 are still lacking. In this study, four T cell epitopes were identified by using wild-type Cra a 1 (wtCra a 1)-immunized mouse splenocytes cultured with synthetic peptides. The immunoreactivity was maintained after chemical denaturation treatment, indicating that the linear epitope is an immunodominant epitope of wtCra a 1. Furthermore, the hypoallergenic derivative (mCra a 1) was developed by the deletion of linear B cell epitopes and retention of T cell epitopes. mCra a 1 could stimulate CD4+T cell proliferation and upregulate interleukin-10 secretion. Overall, basophil activation by mCra a 1 was low, but its ability to induce T cell proliferation was retained, suggesting that mCra a 1 may serve as a viable candidate for treating oyster allergy.
Subject(s)
Allergens , Crassostrea , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Animals , Mice , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/genetics , Allergens/immunology , Allergens/chemistry , Allergens/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/genetics , Crassostrea/immunology , Crassostrea/chemistry , Crassostrea/genetics , Tropomyosin/immunology , Tropomyosin/genetics , Tropomyosin/chemistry , Mice, Inbred BALB C , Female , Humans , Cell Proliferation/drug effects , CD4-Positive T-Lymphocytes/immunology , Shellfish Hypersensitivity/immunology , T-Lymphocytes/immunology , T-Lymphocytes/drug effectsABSTRACT
Sarcoplasmic calcium-binding protein (Cra a 4) from Crassostrea angulata belongs to the EF-hand superfamily, and understanding of its structure-allergenicity relationship is still insufficient. In this study, chemical denaturants were used to destroy the structure of Cra a 4, showing that disruption of the structure reduced its IgG-/IgE-binding activity. To explore which critical amino acid site affects the allergenicity of Cra a 4, the mutants were obtained by site-directed mutations in the disulfide bonds site (C97), conformational epitopes (I105, D114), or Ca2+-binding region (D106, D110) and their IgG-/IgE-binding activity was reduced significantly using serological tests. Notably, C97A had the lowest immunoreactivity. In addition, two conformational epitopes of Cra 4 were verified. Meanwhile, the increase of the α-helical content, surface hydrophobicity, and surface electrostatic potential of C97A affected its allergenicity. Overall, the understanding of the structure-allergenicity relationship of Cra a 4 allowed the development of a hypoallergenic mutant.
ABSTRACT
The meta-analysis aimed to systematically evaluate all the available pieces of evidence concerning the clinical effectiveness of Er,Cr:YSGG lasers (erbium, chromium, yttrium scandium gallium garnet laser) in the non-surgical treatment of patients with chronic periodontitis, and provide guidance for clinicians about the application of Er,Cr:YSGG lasers during the process of non-surgical periodontal treatments. The meta-analysis was conducted with data extracted from 16 randomized controlled clinical trials (RCTs) that compare Er,Cr:YSGG lasers adjunct/substitute to scaling and root planing (SRP) with SRP alone for the treatment of chronic periodontitis published in English or Chinese from January 2000 to January 2020. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were counted for probing depth (PD) reduction, clinical attachment level (CAL) gain, and visual analogue scale (VAS) score. Heterogeneity of each study was evaluated with the Q test. The publication bias was measured using Begg's adjusted rank correlation test. Sixteen RCTs with 606 patients were included in the meta-analysis. There were statistically significant differences between Er,Cr:YSGG lasers adjunct/substitute to SRP and SRP alone in the PD reduction at 1-month follow-up (WMD = 0.35, 95% CI [- 0.63, 0.07], P = 0.013), 3-month follow-up (WMD = - 0.342, 95% CI [- 0.552, - 0.132], P = 0.001), CAL gain at 3-month follow-up (WMD = - 0.17, 95% CI [- 0.31, 0.03], P = 0.017), and VAS score (WMD = - 2.395, 95% CI [- 3.327, - 1.464], P = 0.000) immediately after treatment. There were no significant differences of PD reduction and CAL change at 6-month follow-up. The present meta-analysis indicated that Er,Cr:YSGG lasers provided additional effectiveness in PD reduction and CAL gain at short-term follow-ups and there was less pain compared with SRP alone.
Subject(s)
Chronic Periodontitis/radiotherapy , Lasers, Solid-State/therapeutic use , Randomized Controlled Trials as Topic , Humans , Treatment OutcomeABSTRACT
Peroxiredoxins (Prxs) are potential therapeutic targets for major diseases such as cancers. However, isotype-specific inhibitors remain to be developed. We report that adenanthin, a diterpenoid isolated from the leaves of Rabdosia adenantha, induces differentiation of acute promyelocytic leukemia (APL) cells. We show that adenanthin directly targets the conserved resolving cysteines of Prx I and Prx II and inhibits their peroxidase activities. Consequently, cellular H(2)O(2) is elevated, leading to the activation of extracellular signal-regulated kinases and increased transcription of CCAAT/enhancer-binding protein ß, which contributes to adenanthin-induced differentiation. Adenanthin induces APL-like cell differentiation, represses tumor growth in vivo and prolongs the survival of mouse APL models that are sensitive and resistant to retinoic acid. Thus, adenanthin can serve as what is to our knowledge the first lead natural compound for the development of Prx I- and Prx II-targeted therapeutic agents, which may represent a promising approach to inducing differentiation of APL cells.