Allergologia et immunopathologia最新文献

Background: ACT001 is a potent anti-inflammatory small-molecule drug. However, the single cell and spatial molecular basis of pyroptosis and whether ACT001 exerts a therapeutic effect by preventing pyroptosis on acute lung injury (ALI) remains unclear.

Methods: The bioinformatics approach was employed to identify single cell and spatial landscape of nucleotide-binding domains and leucine-rich repeat protein 3 (NLRP3)-dependent pyroptosis in lipopolysaccharide (LPS) and influenza virus-induced ALI. Molecular docking was performed to elucidate the relationship between ACT001 and NLRP3. LPS-induced ALI mice model was established. Histopathological analysis and bronchoalveolar lavage fluid collection were conducted to investigate the anti-inflammatory and protective effects. In vitro experiments were also performed on bone marrow-derived macrophages to explore the effect of ACT001 on the balance of mitochondrial fusion and fission protein.

Results: Single cell transcriptomic and spatial transcriptomic analysis predicted that NLRP3-dependent pyroptosis significantly correlated with the development of ALI both in single cell and spatial distribution. Molecular docking provided a stable and reliable docking between ACT001 and NLRP3. ACT001 improved the 7-day survival of mice by approximately 50% over the loading dose of LPS-induced ALI. ACT001 (5 uM) attenuated the disruption of mitochondrial integrity and reactive oxygen species. Further, ACT001 reduced the overexpression of the mitochondrial fission protein DRP1 without affecting fusion protein Mitofusin2 levels. Moreover, ACT001 exerted a similar protective effect of suppressing pyroptosis as the DRP1-inhibitor Mdivi-1.

Conclusions: Our study revealed that pyroptosis genes were highly expressed in single-cell and spatial mapping along the first week of ALI occurrence. ACT001 attenuates ALI by reducing the NLRP3-dependent pyroptosis and balancing mitochondrial fission and fusion.

Allergic rhinitis (AR), a type of chronic inflammatory disease that exists in the nasal mucosa, significantly impacts the quality of life. DDX3Y gene encodes an RNA helicase belonging to the DEAD-box protein family and is part of the DDX3 subfamily that affects the progression of multiple diseases. However, the specific role and mechanisms of DDX3Y in AR remain unclear. This study investigates the effects of DDX3Y knockdown on ovalbumin (OVA)-induced AR in mice. We found that DDX3Y is highly expressed in the nasal mucosa of AR mice. Knockdown of DDX3Y in OVA-induced AR mice significantly alleviated nasal manifestations, reduced immunoglobulin E and histamine levels, and improved nasal mucosal histopathology. Additionally, knockdown of DDX3Y suppressed secretion of inflammatory factor nuclear factor kappa B (NF-κB) phosphorylation, thereby mitigating local inflammatory responses. These findings suggested that targeting DDX3Y could offer a novel therapeutic strategy for managing AR by modulating the NF-κB pathway.

Background: Chronic obstructive pulmonary disease (COPD) is a grievous disease that adversely affects human health and life. β-elemene is a type of sesquiterpenoid extracted from Curcuma wenyujin (Zingiberaceae) and displays effects on suppressing tumor growth. However, the regulatory impact of β-elemene in COPD development is not reported.

Objective: This study explored the functioning of β-elemene in the progression of COPD.

Material and methods: The cell survival rate was confirmed through Cell Counting Kit-8 (CCK-8) assay. The cell apoptosis was evaluated through flow cytometry. The protein expressions were examined through western blot. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were examined through the corresponding commercial kits. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β were inspected through Enzyme-Linked Immunosorbent Assay (ELISA).

Results: The study demonstrated that β-elemene exaggerated cell viability and reduced cell apoptosis in BEAS-2B human bronchial epithelial cell line stimulated by cigarette smoke extract (CSE). Oxidative stress was heightened after 5% CSE induction, but this impact was counteracted by β-elemene treatment. In addition, enhancive inflammation induced by cigarette smoke was attenuated by β-elemene treatment. Finally, our results indicated that the triggered the phosphatidylinositol 3-kinase-protein kinase B-mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway mediated by cigarette smoke was refrained by β-elemene treatment.

Conclusion: It was concluded that β-elemene reduced cigarette smoke-triggered inflammation, apoptosis, and oxidative stress in human bronchial epithelial cell line, and refrained PI3K/AKT/mTOR signaling pathway. This study proposed that β-elemene could act as a hopeful drug for the treatment of COPD.

Background: Despite the presence of robust evidence, there is very limited data on the efficacy of allergen immunotherapy (AIT) for selected patients. Accordingly, we aimed to evaluate the efficacy and perceived satisfaction of a 3-year course of sublingual immunotherapy (SLIT) in a paediatric population with allergic rhinitis and/or asthma.

Methods: A pilot, monocentre, retrospective cohort study was performed. One hundred fifty-three children who fulfilled the criteria for allergic rhinitis and asthma and were either mono- or poly-sensitized were enrolled. A standardized questionnaire assessing perceived efficacy, use of rescue medication, disease control, number of exacerbations, quality of life, and perceived satisfaction was administered to each patient.

Results: Seventy patients (49 males, 21 females; mean age, 14.3±1.9 years) were included in the final analysis. All 70 patients received SLIT for up to 3 years, with 100% adherence to the treatment throughout the study. Significant improvements in symptoms and quality of life were reported (p<0.01). There was also a significant decrease in disease severity, use of rescue medication, and sleep disturbances (p<0.01). Additionally, a significant improvement in school performance was also recorded (p<0.01). Of the enrolled patients, 60 out of 70 (85.7%) reported being very satisfied, 6 out of 70 (8.57%) were much satisfied, and 4 out of 60 (5.71%) were satisfied.

Conclusions: We were the first to demonstrate the efficacy and perceived satisfaction of a 3-year SLIT in a paediatric population, with 100% treatment adherence throughout the study.

Background: Asthma is one of the most prevalent chronic respiratory diseases among children, markedly impairing patient's health and imposing an increasing burden on the healthcare system. Several traditional Chinese medicines have demonstrated efficacy in alleviating asthma symptoms through studies conducted on animal models. Recent studies have shown that the Yunpi Xiefei Huatan Tang decoction (YPD) exhibits significant therapeutic outcomes in treating phlegm-obstructed pulmonary asthma. However, the precise regulatory effects of YPD on the progression of asthma require additional investigation.

Objective: To explore the functions of YPD in asthma progression.

Material and methods: The asthma rat model triggered by ovalbumin (OVA) was established successfully. The pathological changes of lung tissues were examined through Hematoxylin and Eosin (H&E) staining. The levels of Interleukin 6 (IL-6) and IL-1β were tested through Enzyme-Linked-Immunosorbent Serologic Assay (ELISA). The number of total cells or eosinophils in bronchoalveolar lavage fluid was confirmed through cell counter. The collagen deposition in bronchi was assessed through Masson staining. The protein expressions were measured through western blot.

Results: This study demonstrated that YPD could mitigate airway inflammation in an OVA-triggered asthma rat model. Furthermore, YPD was found to decrease the production of inflammatory cytokines in the lungs and suppress the infiltration of inflammatory cells into bronchoalveolar lavage fluid. Additionally, the airway remodeling stimulated by OVA could be suppressed following YPD treatment. Finally, it was disclosed that YPD inhibited the wingless-related integration site-beta-catenin (Wnt/β-catenin) signaling pathway in the OVA-stimulated asthma rat model.

Conclusion: YPD alleviated airway inflammation and remodeling in asthmatic mice via the Wnt/β-catenin signaling pathway. This research offers significant insights into the potential application of YPD in the treatment of asthma.

Introduction: We aimed to investigate the frequency and sociodemographic and clinical distinguishing features of asthmatic patients in whom long-acting muscarinic antagonists (LAMA) were added to maintenance therapy in our clinic.

Methods: In this cross-sectional study, data on sociodemographic, phenotypic, and clinical characteristics of patients with asthma using Steps 4 and 5 medications, who were followed up in our center for at least 1 year, were obtained from file records. Whether the patients received add-on LAMA for at least 6 months was also noted.

Results: A total of 279 patients with asthma using Steps 4 and 5 medications (female/male: 215/64) with a mean age of 50.84 ± 12.42 years were included in the study. Seventy-nine (28.3%) patients (female/male: 60/19) with a mean age of 52.45 ± 11.61 years used LAMA as an add-on treatment; 28 (37.8%) at Step 4 and 51 (24.8%) at Step 5. In Steps 4 and 5, there was no difference in terms of age, sex, body mass index, smoking status, being allergic or eosinophilic, phenotype, and asthma onset between patients with and without add-on LAMA. Asthma control in the previous year was better, and minimum forced expiratory volume in 1s (FEV1) was lower in patients with LAMA than in those without in Step 4 (P = 0.001 and P = 0.030, respectively). In Step 5, the rate of being well-controlled was higher in those without add-on LAMA (P < 0.001). The number of exacerbations in the previous year was higher, and minimum and maximum FEV1 were lower in patients with add-on LAMA (P < 0.001 and P < 0.001, respectively).

Conclusion: Our study showed that add-on LAMA treatment was effective in increasing asthma control in patients using Step 4 medication independent of baseline characteristics and asthma phenotype.

Introduction: A patient was presented with a history of idiopathic recurrent anaphylaxis after administration of Pfizer BioNTech mRNA vaccine, and the attacks were controlled with omalizumab. To our knowledge, this is the first reported case of recurrent idiopathic anaphylaxis (IA) after administration of Pfizer BioNTech mRNA vaccine.

Case presentation: A 52-year-old man with recurrent episodes of IA after COVID-19 vaccination presented to our adult Allergy and Immunology Clinic. In the patient, urticaria and anaphylaxis episodes could not be controlled with high-dose antihistamine and systemic steroid treatment, and complete control was achieved with omalizumab treatment and anaphylaxis attacks completely regressed.

Conclusion: In cases of unexplained or recurrent anaphylaxis in adult patients, COVID-19 vaccination and timing should be questioned, and its association with anaphylaxis might be considered.

In coronary microembolization, inflammatory cell infiltration, patchy necrosis, and extensive intra-myocardial hemorrhage are dominant, which induce myocardial dysfunction with clinical symptoms of chronic ischemic cardiomyopathy. Microembolization can lead to obstruction of the coronary microvessels and result in the micro-infarction of the heart. The inflammation and elevated expression of the tumor necrosis factor in cardiomyocytes and the activation of extracellular ERK are involved in initiating the inflammatory response mechanism. The PI3K/Akt signaling pathway is the enriched pathway, and for controlling, inhibition of PI3K/Akt is necessary. Furthermore, the release of cytokines and the activation of inflammasomes contribute to the enhancement of vascular permeability, which results in edema within the myocardium. The immune response and inflammation represent the primary triggers in this process. The ability to control immune response and inflammation reactions may lead to the development of new therapies for microembolization.

Background: Allergies to fungi, such as Alternaria alternata, are significant contributors to respiratory conditions like asthma and rhinitis. Immunotherapy with native A. alternata extracts often results in high rates of adverse reactions. This study evaluates the safety of immunotherapy using glutaraldehyde-polymerized A. alternata extracts in both pediatric and adult populations.

Methods: This observational real-world study involved 738 patients (435 children and 303 adults) monosensitized to A. alternata or polysensitized together to other allergens. Patients received personalized immunotherapy containing polymerized A. alternata extract, either alone or in combination with other polymerized allergens. The concentration of each polymerized allergen in the therapeutic vaccine was 10,000 TU/mL. Side reactions were classified and recorded based on immediate and delayed onset, and their severity was graded according to the EAACI guidelines.

Results: All side reactions were expected and related to the intrinsic properties of allergens. The number of injections administered was 7392, with 4137 to children and 3255 to adults. Thirteen relevant local reactions (0.24% in children, 0.09% in adults) and seven systemic reactions (0.09% overall) were observed. Systemic reactions included mild to moderate symptoms, such as mild bronchospasm and rhinitis. Severe reactions were not reported.

Conclusion: Immunotherapy with glutaraldehyde-polymerized A. alternata, alone or in combination with other polymerized allergens, is safe and well-tolerated in both children and adults. The polymerized extracts allow for higher concentrations and faster administration schedules, providing an effective treatment option for patients with fungal allergies, including those polysensitized to multiple allergens.