Increased Nasal Blimp1 + Treg Cells After Sublingual Immunotherapy Reflect the Efficacy of Treatment in Allergic Rhinitis.

INTRODUCTION: Allergen-specific immunotherapy (AIT) plays a pivotal role in altering the immune status and tissue responses in allergic rhinitis (AR). This study focuses on the impact of sublingual immunotherapy (SLIT) involving dust mite drops, exploring the modulation of regulatory T cells (Treg) and their specific marker, BLIMP1, in the nasal mucosa. METHODS: Immune cells were isolated from nasal lavage fluid of patients with AR undergoing SLIT (n = 94). Treg cells were analyzed for BLIMP1 expression, and chemokine levels associated with Treg recruitment were assessed using Luminex assay. Patients were categorized on the basis of SLIT efficacy and followed for changes after discontinuation. RESULTS: SLIT induced a significant increase in nasal Treg cells (7.09 ± 2.59% vs. 0.75 ± 0.27%, P < 0.0001). BLIMP1 expression in Treg cells notably increased after SLIT (0.36 ± 0.22% to 16.86 ± 5.74%, P < 0.0001). Ineffective SLIT cases exhibited lower levels of nasal Treg and Blimp1 + Treg cells (both P < 0.0001). Receiver operating characteristic (ROC) analysis confirmed their potential as efficacy predictors (AUC = 0.908 and 0.968, respectively). SLIT discontinuation led to a significant reduction in Treg and Blimp1 + Treg cells (P < 0.001), emphasizing their maintenance during treatment. Pro-inflammatory cytokines decreased (P < 0.001), while CCL2 associated with Treg recruitment increased (P = 0.0015). CONCLUSION: Elevated nasal Blimp1 + Treg cells serve as a predictive biomarker for SLIT responsiveness in pediatric AR. Their influence on immunotherapy effectiveness contributes to a nuanced understanding of SLIT mechanisms, allowing for disease stratification and personalized treatment plans. This study offers scientific support for predicting SLIT efficacy, enhancing the prospects of improved treatment outcomes in AR.

Metal-Coordinated Covalent Organic Frameworks as Advanced Bifunctional Hosts for Both Sulfur Cathodes and Lithium Anodes in Lithium-Sulfur Batteries.

The shuttling of polysulfides on the cathode and the uncontrollable growth of lithium dendrites on the anode have restricted the practical application of lithium-sulfur (Li-S) batteries. In this study, a metal-coordinated 3D covalent organic framework (COF) with a homogeneous distribution of nickel-bis(dithiolene) and N-rich triazine centers (namely, NiS4-TAPT) was designed and synthesized, which can serve as bifunctional hosts for both sulfur cathodes and lithium anodes in Li-S batteries. The abundant Ni centers and N-sites in NiS4-TAPT can greatly enhance the adsorption and conversion of the polysulfides. Meanwhile, the presence of Ni-bis(dithiolene) centers enables uniform Li nucleation at the Li anode, thereby suppressing the growth of Li dendrites. This work demonstrated the effectiveness of integrating catalytic and adsorption sites to optimize the chemical interactions between host materials and redox-active intermediates, potentially facilitating the rational design of metal-coordinated COF materials for high-performance secondary batteries.

Multicenter study of seasonal and regional airborne allergens in Chinese preschoolers with allergic rhinitis.

This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P < 0.01). Children with only pollen sensitization had higher cumulative rhinitis symptom scores than the all-negative group (P < 0.0001) and the mite-only sensitization group [P < 0.05], while the mite-only sensitization group also had higher scores than the all-negative group [P < 0.05], and the group sensitized to both pollen and mites had lower scores than the pollen-only group [P < 0.05]. This study indicates that sensitization to mites and grass pollens exhibits significant regional differences, with grass pollen allergies primarily occurring in autumn, sensitization to pollens in general exhibits a pronounced seasonal pattern. Moreover, pollen sensitization aggravates nasal and ocular symptoms in AR children.

Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy.

INTRODUCTION: Our prior clinical study assessed the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farina drops on patients with allergic rhinitis (AR) while analyzing the characteristics of adverse reactions. This study was conducted to evaluate the immune cell composition alterations in AR patients before and after SLIT, and to comprehensively investigate the role and changes of antigen-specific immune cells associated with treatment efficacy. METHODS: A total of 68 AR patients who completed 12 months of SLIT were included in the study. Before the trial's initiation and after 1 year of SLIT, 10 ml of venous blood was collected. Peripheral blood mononuclear cells were isolated using the Ficoll gradient method. The mRNA transcriptome was analyzed using an Affymetrix microarray. The proportions of 22 immune cell types were calculated via the CIBERSORTx platform. Correlations between each immune cell type and SLIT were analyzed. PI3K-PKB pathway dysregulation were analyzed using quantitative PCR and Western blot. Flow cytometry was utilized to assess the percentages of Th1 and Th2 cells. RESULTS: Mono-sensitized AR patients exhibited marked increases in plasma cells, activated memory T cells, regulatory T cells, and activated dendritic cells, while experiencing decreased neutrophils and resting dendritic cells. In poly-sensitized AR patients, the most notable change was an increase in regulatory T cells, coupled with decreased T follicular helper cells, resting dendritic cells, and activated mast cells. These findings indicated that SLIT reshaped immune cell profiles in AR patients, and, notably, the specific changes differed between mono-sensitized and poly-sensitized individuals. Furthermore, SLIT appeared to shift the immune response towards a Th2 decrease profile in both groups. Importantly, suppression of the PI3K-PKB pathway was evidenced as inhibition of PKB phosphorylation and the decrease of glycogen synthase kinase 3 ß (GSKß) and mammalian target of rapamycin (mTOR) expression after SLIT. CONCLUSION: Our study has demonstrated that SLIT treatment led to distinct changes in immune cell profiles between mono-sensitized and poly-sensitized AR patients. Furthermore, SLIT appeared to reduce a Th2 immune response, highlighting its efficacy in AR treatment. Importantly, the study revealed the suppression of the PI3K-PKB pathway, shedding light on the immunological mechanisms underlying SLIT's effectiveness.

Bicalutamide, an androgen receptor antagonist, effectively alleviate allergic rhinitis via suppression of PI3K-PKB activity.

OBJECTIVES: To investigate the therapeutic effect of Bicalutamide, an androgen receptor antagonist on the onset and development of allergic rhinitis in an animal model. METHODS: 40 male BALB/c mice were randomly divided into five groups (eight mice per group). Aluminum hydroxide powder was used as an adjuvant, combined with Ovalbumin (OVA) to establish the mouse model of allergic rhinitis via ultrasonic nebulization of OVA to stimulate the nasal cavity. Mice in Bica#1 group were intraperitoneally injected with 0.02 mg Bicalutamide/0.5 ml of normal saline daily for 7 consecutive days; mice in Bica#2 group were administered 0.02 mg Bicalutamide/0.5 ml of normal saline via intraperitoneal injection for 5 consecutive days, and then the same amount of normal saline was injected intraperitoneally for 2 consecutive days. Enzyme-linked immunosorbent assay was adopted to detect the serological levels of IgE, IL-4, and IL-6 production. Eosinophil infiltration was observed under microscope after hematoxylin and eosin staining of nasal mucosa. Quantitative PCR and Western blot were employed for determination of histamine receptors mRNA expression and PI3K/PKB associated protein levels, respectively. RESULTS: Histological analysis shown that allergic lesion was induced after OVA sensitization. Intraperitoneal injection with 0.02 mg Bicalutamide daily for 7 consecutive days significantly reduced the allergic lesion; however, mice injected with the same amount of normal saline at the same time demonstrated no allergic rhinitis symptoms. In addition, there was a significant reduction in eosinophils number in Bicalutamide treated mice (n = 8) compared to the OVA group (n = 8) (OVA: 19.6 ± 5.3 vs. Bica#1: 7.7 ± 0.8 vs. Bica#2: 9.4 ± 1.2, both p < 0.01). Furthermore, ELISA results revealed that the serological levels of IgE (OVA: 17.3 ± 1.7 µg/ml vs. Bica#1: 9.2 ± 0.6 vs. Bica#2: 10.4 ± 2.3, both p < 0.05), IL-4 (OVA: 164.3 ± 5.1 pg/ml vs. Bica#1: 110.2 ± 3.1 vs. Bica#2: 115.3 ± 4.1, both p < 0.05) and IL-6 (OVA: 167.3 ± 3.7 pg/ml vs. Bica#1: 117.5 ± 6.5 vs. Bica#2: 114.8 ± 2.4, both p < 0.05) were significantly decreased after two different dosage of Bicalutamide treatment. Similarly, histamine receptors in mast cells were significantly reduced after two different dosage of Bicalutamide treatment. More importantly, p-PKB protein was notably reduced after two different dosage of Bicalutamide treatment compared to the OVA group, mTOR protein levels were also down regulated after two different dosage of Bicalutamide treatment. CONCLUSIONS: Our data demonstrated that androgen receptor antagonist Bicalutamide can significantly alleviate allergic rhinitis lesion in the animal model. PI3K/PKB activity in mast cells was suppressed after Bicalutamide injection. Our results provide important implication in allergic rhinitis prevention and treatment.

Expression of ANCR in nasopharyngeal carcinoma patients and its clinical significance.

ABSTRACT: Anti-differentiation non-coding RNA (ANCR), a long non-coding RNA, is involved in the development, progression and metastasis of various human cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) still remains unknown. This study aimed to investigate ANCR expression and its clinical significance in NPC.Totally, 96 NPC tissues and 24 non-cancerous nasopharyngeal mucosa tissues were used. The levels of ANCR were determined by qRT-PCR. Relationship of ANCR with patient clinical characteristics, disease-free survival and overall survival (OS) was evaluated.ANCR expression was increased in NPC tissues compared to non-cancerous nasopharyngeal mucosae. ANCR expression was significantly related to lymph node metastasis, clinical stage, and tumor differentiation (P < .05). Kaplan-Meier survival analysis revealed that high level of ANCR expression was significantly associated with poor disease-free survival but not with OS in NPC patients. Univariate analysis showed a significant association between increased ANCR expression and adverse OS (P < .05), but multivariate analysis suggested that ANCR could not be used as an independent prognostic factor for NPC patients.ANCR is involved in the development and progression of NPC, but whether it can be used as an effective therapeutic target for NPC needs further study.

Long noncoding RNA ANCR promotes migration, invasion, EMT progress and stemness of nasopharyngeal carcinoma cells via the miR-4731-5p/NMT1 axis.

BACKGROUND: In our previous study, we revealed that Antidifferentiation noncoding RNA (ANCR) promoted proliferation and radiation resistance of nasopharyngeal carcinoma (NPC) cells. However, the molecular mechanism and function of ANCR are not fully studied. The current study aimed to further investigate the role and underlying molecular mechanism of ANCR in NPC. METHODS: RT-qPCR and western blot analyses were used to detect the levels of RNAs and proteins in NPC cells. Wound healing and Transwell assays were used to examine the migration and invasion of NPC cells. The relationship among ANCR, miR-4731-5p and N-myristoyltransferase 1 (NMT1) was investigated by RIP and luciferase reporter assays. The NPC cell stemness was accessed by the sphere formation assay. RESULTS: ANCR was significantly highly expressed in NPC cell lines. Silenced ANCR suppressed cell migration, invasion epithelial-mesenchymal transition (EMT) process and cell stemness in NPC. Furthermore, ANCR sponged miR-4731-5p to upregulate the NMT1 expression. Rescue assays indicated that NMT1 neutralized the antioncogenic effect induced by silenced ANCR on NPC cells. CONCLUSIONS: Long noncoding RNA ANCR suppresses malignant behaviors of nasopharyngeal carcinoma cells by regulating miR-4731-5p/NMT1 axis.

A Retrospective Cohort Study of Sublingual Immunotherapy with Standardized Dermatophagoides farinae Drops for Allergic Rhinitis.

INTRODUCTION: To evaluate the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farinae (Df) drops in monosensitized and polysensitized patients with allergic rhinitis (AR) and to analyze the adverse events (AEs). METHODS: A retrospective analysis was performed using data for 68 patients with AR who received SLIT. The patients were divided into a monosensitized group (36 cases) and a polysensitized group (32 cases) based on serum-specific IgE test results. In the two groups of patients, total nasal symptoms score (TNSS), total medication score (TMS), visual analog scale (VAS) score, and AEs before treatment and at 1, 3, 6, and 12 months of treatment were evaluated. RESULTS: Compared with that before treatment, the TNSS, TMS, and VAS score in the monosensitized and polysensitized groups all decreased significantly at 3, 6, and 12 months of SLIT (all P < 0.05). There were no significant differences in treatment efficacy indicators between the two groups at all treatment time points (all P > 0.05). In terms of safety, compared with 1 month after initiating SLIT, the incidence of AEs in the monosensitized and polysensitized groups at 6 and 12 months of treatment significantly decreased (all P < 0.05). There was a statistically significant decrease in the incidence of AEs in both groups at 6 months compared with 3 months of treatment (χ2 = 1.92 and 5.85, respectively, all P < 0.05). The difference in incidence of AEs between the monosensitized and polysensitized groups was not statistically significant at any treatment time point (all P > 0.05). AEs in all patients were local mild reactions; no serious AEs were found. CONCLUSION: SLIT with standardized Df drops has similar efficacy and safety for monosensitized and polysensitized patients with AR. AEs mostly occurred during the first 3 months of SLIT in both the monosensitized and polysensitized groups, and the incidence of AEs gradually decreased as the course of treatment extended.

The NRF2/KEAP1 Pathway Modulates Nasopharyngeal Carcinoma Cell Radiosensitivity via ROS Elimination.

PURPOSE: Radioresistance is a vital obstacle for the prognosis of human nasopharyngeal carcinoma (NPC), but the underlying mechanism is still unknown. Here, we explored the role of the NRF2/KEAP1 pathway in radioresistance of NPC cell lines. MATERIALS AND METHODS: We selected NPC cell lines CNE-1 and CNE-2, treated them with ionization, and subsequently determined the levels of NRF2, KEAP1, antioxidant enzymes, and ROS. We then evaluated the effect of NRF2 or KEAP1 inhibition on cell proliferation, colony formation, and radiosensitivity in CNE2 cells. RESULTS: We discovered that the NRF2/KEAP1 signaling pathway can be activated by radiotherapy in NPC cells, while NRF2 knockdown enhances the sensitivity of CNE-2 cells to radiation treatment. In contrast, the silencing of KEAP1 inhibits the sensitivity of CNE-2 cells to radiation treatment. CONCLUSION: Our results suggest that NRF2/KEAP1 signaling may serve as an essential regulator of the radioresistance of NPC and may be applied as a novel therapeutic approach for the sensitization of NPC to radiation.

Anti-allergic function of alpha-Tocopherol is mediated by suppression of PI3K-PKB activity in mast cells in mouse model of allergic rhinitis

BACKGROUND: Alpha-Tocopherol (alpha -TCP), one major form of vitamin E, has been known as a treatment for airway allergic inflammation. However, the role and mechanism of alpha-TCP in treating allergic rhinitis remains unclear. OBJECTIVE: In this study we examined the inhibitory function of alpha-TCP in a mouse model of allergic rhinitis. METHODS: Allergic phenotype was examined by hematoxylin and eosin staining. Total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were examined by ELISA. mRNA expression was measured by qPCR, protein levels were examined by Western Blot. RESULTS: Histological analysis of the nasal membranes revealed that there was a significant reduction in inflammatory cells appearance in cross-sections in alpha-TCP treatment of Ovalbumin (OVA)-sensitized mice compared to OVA sensitized animals. In addition, eosinophils were significantly reduced in nasal mucosa of alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Lower total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were found in alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Furthermore, we found that the subepithelial distribution of tryptase positive mast cells was reduced in the alpha-TCP treatment of OVA-sensitized mice. More importantly, the PI3K-PKB pathway was suppressed by alpha-TCP in mast cells. CONCLUSIONS: Our results demonstrated that α-TCP-mediated suppression of PI3K-PKB activity in mast cells is a potential mechanism of anti-allergic function of alpha-TCP

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