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The pathologic feature of food allergy (FA) is the aberrant Th2‐biased immune response in the intestine. Regulatory T cells (Tregs) play an important role in the suppression of aberrant immune response. The activities of the TLRs regulate multiple cell functions. This study aims to investigate the role of TLR3 activation in the regulation of Th2‐biased immune response in the intestine by the generation of inducible Tregs (iTregs). In this study, polyinosinic polycytidylic acid (polyI:C) was used as an activator of TLR3. An FA mouse model was developed to establish the Th2‐biased inflammation in the intestine. The effects of TLR3 activation on the generation of iTreg were tested in the culture and in mice. We observed that exposure to polyI:C induced IFN‐γ+ Foxp3+ iTregs in mouse intestine and in the culture. The IFN‐γ+ Foxp3+ iTregs showed immune suppressive functions. Exposure to polyI:C increased T‐bet levels in CD4+ T cells. The T‐bet formed a complex with GATA3 to dissociate Foxp3 from GATA3/Foxp3 complex in CD4+ T cells. The Foxp3 thus gained the opportunity to move to TGF‐β promoter to generate iTregs. Administration with polyI:C prevented the development of FA and inhibited existing FA. In conclusion, activation of TLR3 induces IFN‐γ+ Foxp3+ Tregs, which can prevent FA development and inhibit existing FA in mice. [ABSTRACT FROM AUTHOR]

Background Acute myocardial infarction (AMI) is one of the leading causes for death in both developed and developing countries and it is the single largest cause of death in the United States, responsible for 1 out of every 6 deaths. The objective of this study was to determine microRNA (miRNA) expression in AMI and determine whether miR-133, miR-1291 and miR-663b could be measured in plasma as a biomarker for recurrence. Methods Patients with AMI and those without AMI were retrospectively recruited for a comparison of their plasma miR-133, miR-1291 and miR-663b expression. Results miR-133, miR-1291 and miR-663b levels were significantly overexpressed in AMI compared with Non-AMI. MiR-133 showed an AUC of 0.912, with a sensitivity of 81.1% and a specificity of 91.2%. The AUC for miR-1291 was 0.695, with a sensitivity of 78.4% and a specificity of 89.5%. The AUC for miR-663b was 0.611, with a sensitivity of 72.4% and a specificity of 76.5%. Conclusions This study demonstrated that the levels of miR-133, miR-1291 and miR-663b are associated with AMI. The potential of these miRNAs as biomarkers to improve patient stratification according to the risk of AMI and as circulating biomarkers for the AMI progonos warrants further study. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8183629061241474 [ABSTRACT FROM AUTHOR]

Allergic diseases like asthma, allergic rhinitis and dermatitis pose a significant global health burden, driving the search for novel therapies. The NLRP3 inflammasome, a key component of the innate immune system, is implicated in various inflammatory diseases. Upon exposure to allergens, NLRP3 undergoes a two-step activation process (priming and assembly) to form active inflammasomes. These inflammasomes trigger caspase-1 activation, leading to the cleavage of pro-inflammatory cytokines (IL-1β and IL-18) and GSDMD. This process induces pyroptosis and amplifies inflammation. Recent studies in humans and mice strongly suggest a link between the NLRP3 inflammasome, IL-1β, and IL-18, and the development of allergic diseases. However, further research is needed to fully understand NLRP3's specific mechanisms in allergies. This review aims to summarize the latest advances in NLRP3 activation and regulation. We will discuss small molecule drugs and natural products targeting NLRP3 as potential therapeutic strategies for allergic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Zhou, Hu, Yang, Wang, Luo, Qiu, Cheng and Zeng.)

The pathologic feature of food allergy (FA) is the aberrant Th2-biased immune response in the intestine. Regulatory T cells (Tregs) play an important role in the suppression of aberrant immune response. The activities of the TLRs regulate multiple cell functions. This study aims to investigate the role of TLR3 activation in the regulation of Th2-biased immune response in the intestine by the generation of inducible Tregs (iTregs). In this study, polyinosinic polycytidylic acid (polyI:C) was used as an activator of TLR3. An FA mouse model was developed to establish the Th2-biased inflammation in the intestine. The effects of TLR3 activation on the generation of iTreg were tested in the culture and in mice. We observed that exposure to polyI:C induced IFN-γ + Foxp3 + iTregs in mouse intestine and in the culture. The IFN-γ + Foxp3 + iTregs showed immune suppressive functions. Exposure to polyI:C increased T-bet levels in CD4 + T cells. The T-bet formed a complex with GATA3 to dissociate Foxp3 from GATA3/Foxp3 complex in CD4 + T cells. The Foxp3 thus gained the opportunity to move to TGF-β promoter to generate iTregs. Administration with polyI:C prevented the development of FA and inhibited existing FA. In conclusion, activation of TLR3 induces IFN-γ + Foxp3 + Tregs, which can prevent FA development and inhibit existing FA in mice., (©2019 Society for Leukocyte Biology.)

Immune dysregulation, such as defects in immune suppressor function, plays an important role in the pathogenesis of many immune disorders including allergic rhinitis (AR). Some Chinese traditional medical formulae have an immune regulatory function. This study aims to restore the immune suppressor function in regulatory B cells (Bregs) collected from AR patients with a Chinese medical formula, Yupingfeng San (YPFS). In this study, Bregs were isolated from blood samples collected from AR patients and healthy (HA) subjects. The capacity of Breg in suppressing effector T cell (Teff) proliferation was observed in an in vitro experiment to be used as an indicator of immune suppressor function of Breg. The effects of YPFS on promoting Bregs' immune suppressor functions were tested in a cell culture study. The results showed that the number of peripheral Breg in AR patients was not significantly different from that in HA subjects, while the immune suppressor function of AR Breg was compromised. Bcl2L12 expression was higher in AR Bregs than that in HA Bregs. A negative correlation was identified between expression of Bcl2L12 and IL-10 in AR Bregs. Exposure of AR Bregs to YPFS in the culture suppressed the expression of Bcl2L12 and improved their immune suppressor function. In conclusion, YPFS can restore the immune suppressor function of AR Bregs via inhibiting the expression of Bcl2L12. The data suggest that YPFS has the potential to be used in the improvement of immune dysfunction, such as AR., Competing Interests: None.

The Th2-biased inflammation and immune deregulation play a critical role in the pathogenesis of ulcerative colitis (UC). Recent studies indicate that the Bcl2-like protein 12 (Bcl2L12) is associated with immune deregulation of UC. This study aims to investigate the role of Bcl2L12 in the induction of aberrant Th2-biased inflammation. In this study, peripheral blood samples were collected from patients with inflammatory bowel disease. The Th2 cell activities were analyzed by flow cytometry, real-time quantitative RT-PCR, and Western blotting. Mice with Bcl2L12-knockout CD4 + T cells were used in the experiments. The results showed that the expression of Bcl2L12 was detected in peripheral CD4 + T cells, which was significantly higher in UC patients than in healthy subjects. A positive correlation between the expression of Bcl2L12 and Th2 cytokines was detected in CD4 + T cells from UC patients. Naive CD4 + T cells with Bcl2L12 overexpression were prone to differentiate into Th2 cells. Mice with Bcl2L12 deficiency failed to induce the Th2-biased inflammation in the intestine. Bcl2L12 bound GATA3 to form a complex to enhance the binding between GATA3 and the Il4 promoter to enhance the expression of IL-4 in CD4 + T cells. CD4 + T cells with Bcl2L12 overexpression were resistant to apoptosis. In conclusion, the Bcl2L12 is a critical factor in the induction of aberrant Th2 polarization by upregulating Th2 responses and downregulating Th2 cell apoptosis. Bcl2L12 may be a novel therapeutic target in the management of the disorders with Th2-biased inflammation., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Dysiarenone (1), a dimeric C 21 meroterpenoid featuring an unprecedented 2-oxaspiro[bicyclo[3.3.1]nonane-9,1'-cyclopentane] carbon skeleton, was isolated from the marine sponge Dysidea arenaria. The structure of 1 was determined by HRMS and NMR spectroscopic analyses coupled with ECD calculations. Dysiarenone showed inhibitory activities against COX-2 expression and the production of prostaglandin E 2 with an IC 50 value of 6.4 μM in LPS-stimulated RAW264.7 macrophages.

Objective: To analyze the impact of sublingual immunotherapy(SLIT)on the quality of life in children with allergic rhinitis. Method: Fifty children with allergic rhinitis who have received sublingual immunotherapy were enrolled in this study.Quality of life was evaluated via measurement of VAS score and rhinoconjunctivitis quality of life questionnaire(RQLQ)before and after treatment. Result: Twenty patients after treatment had complete remission,13 cases were partly alleviated and 17 cases had no response.The total effective rate was 66%.The Multi-VAS scores and Uni-VAS scores in each observation time point(at half a year,one year,two years after treatment)had statistically significant difference compared with that of pre-treatment with SLIT( P <0.05).According to RQLQ scores,the quality of life,nasal symptoms,conjunctiva symptoms,non-nasal(ocular)symp-toms,behaviors and emotional responses were greatly improved in each time point compared with that of pretreatment( P <0.05).Symptomatic treatment scores in each time point after treatment were significantly different and had a positive correlation with the scores of RQLQ( P <0.05). Conclusion: SLIT can improve the nasal allergic symptoms,children's life quality and reduce the use of symptomatic treatment medicines.

Background: Bronchopulmonary dysplasia (BPD) in premature infants is a predominantly secondary occurrence to intrauterine inflammation/infection and postpartum mechanical ventilation; The purpose of this study is to explore the biological roles of lincRNA in the pathogenesis of BPD., Methods: Newborn rats were randomly assigned to hyperoxia (85% O 2 ) or the control group: the normoxia group (21% O 2 ). Lung tissues were collected on days 1-14. The BPD animal model was validated using HE staining, Masson staining, and real-time RT-PCR. Deep Illumina sequencing was used to reveal the differential expression of long non-coding RNAs in hyperoxia bronchopulmonary dysplasia rat models. KEGG and GO functions were predicted. Nine possible BPD-related target lincRNAs were verified by RTq-PCR., Results: The histopathologic changes in lung tissues manifested as hyperaemia, edema, hemorrhage, and inflammation cell infiltration after continuous exposure to hyperoxia for 3 days, and became aggravated after 7 days of hyperoxic exposure. The above lung tissue inflammatory manifestations were alleviated and taken over by pulmonary interstitia hyperplasia and fibrocyte proliferation after 14 days of hyperoxic exposure. The expressions of lincRNA differed between the hyperoxia bronchopulmonary dysplasia model group and the normoxia group. 1175 different lincRNAs were detected in the hyperoxia group and the normoxia group, of which 544 were up-regulated and 631 were down-regulated. 673 moleculars related to GO functions were enriched, including cell location and biological process. Pathway enrichment analysis showed that lincRNA was involved in 257 KEGG pathways. 9 lincRNA were validated in the sample, and the difference was statistically significant., Conclusion: LincRNAs were identified differently between the BPD model and the normoxia group. Many target genes were involved in the developmental process, including cell component biogenesis, biological regulation, transcription regulator, and translation regulator. The BPD might be caused by the activation of the pathways of the EMC-receptor interaction, cytokine-cytokine receptor interaction, cell cycle, and cell adhesion molecules. The present study provides new insight into the pathogenesis mechanism of BPD., Competing Interests: None.