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Journal of Stroke and Cerebrovascular... Jul 2024Ischemic stroke remains the predominant contributor to mortality and disability globally. Microglia undergo rapid activation and initiate inflammatory cascade reactions...
BACKGROUND
Ischemic stroke remains the predominant contributor to mortality and disability globally. Microglia undergo rapid activation and initiate inflammatory cascade reactions by phenotypic polarization, participating in the regulation of inflammatory injury and tissue repair post-ischemic stroke. Regulating microglia-mediated neuroinflammation is a promising therapeutic strategy for ischemic stroke. Previously, we designed and synthesized a novel p55PIK inhibitor, TAT-N15 polypeptide, which presents inhibitive activity on NF-κB signaling-mediated inflammation in acute conjunctivitis and allergic rhinitis. The present study aimed to explore the therapeutic effect and mechanism of TAT-N15 on ischemia stroke.
METHODS
The mouse model of transient cerebral ischemia was made using the intraluminal filament method. After being treated with daily intraperitoneal injections of TAT-N15 (10 mg/kg) for 7 d, the neurological outcomes and the cerebral infarction volume were evaluated. Histopathology of the ischemia cerebral hemisphere was observed by H&E and Nissl staining. Neuronal survival, astrogliosis, and co-labeling of CD86/Iba1 and CD206/Iba1 were detected by immunofluorescence. The cell apoptosis was estimated by TUNEL staining. The expression levels of apoptosis-associated proteins, proinflammatory cytokines, protein markers of M1 and M2 microglia, and the phosphorylation of NF-κB and STAT3 proteins in the ischemic penumbra were detected by Western blot.
RESULTS
TAT-N15 treatment significantly decreased the infarct volume and alleviated neurological functional impairment, neuronal injury, and neuron apoptosis. Meanwhile, TAT-N15 treatment restrained the activation of microglia and astrocytes as well as the protein expression of proinflammatory cytokine in ischemic penumbra. Additionally, the administration of TAT-N15 treatment resulted in a significant reduction in the density of M1 phenotype microglia while concurrently increasing the density of M2 phenotype microglia within the ischemic penumbra. Finally, mechanical analysis unveiled that TAT-N15 exerted a substantial inhibitory effect on the protein expression of phosphorylated STAT3 and NF-κB.
CONCLUSION
TAT-N15 may inhibit neuroinflammation via regulating microglia activation and polarization through the STAT3/NF-κB pathway, which exhibits the neuroprotection effect in ischemic stroke.
Topics: Animals; STAT3 Transcription Factor; Signal Transduction; Disease Models, Animal; Microglia; NF-kappa B; Neuroinflammatory Diseases; Neuroprotective Agents; Male; Anti-Inflammatory Agents; Apoptosis; Mice, Inbred C57BL; Inflammation Mediators; Brain; Ischemic Attack, Transient; Ischemic Stroke; Infarction, Middle Cerebral Artery
PubMed: 38679216
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107736 -
Annals of Allergy, Asthma & Immunology... Apr 2024Allergic rhinitis (AR) is a common respiratory disease encompassing a variety of phenotypes. Patients can be sensitized to 1 or more allergens. There are indications...
BACKGROUND
Allergic rhinitis (AR) is a common respiratory disease encompassing a variety of phenotypes. Patients can be sensitized to 1 or more allergens. There are indications that polysensitization is associated with more severe disease. However, the extent to which the level of sensitization is associated with clinical disease variability, underlying the distinct nature of AR from AR+ conjunctivitis or AR+ asthma, is not known.
OBJECTIVE
To evaluate phenotypical differences between monosensitized and polysensitized patients with AR and to quantify their symptomatic variability.
METHODS
A total of 565 patients with a confirmed diagnosis of AR were included in this cross-sectional study. Of those, 155 were monosensitized and 410 were polysensitized. Interactions between sensitization levels and the reporting of different symptoms of AR and co-morbidities, disease duration, and impact were assessed. Furthermore, patients were stratified into monosensitized, oligosensitized, and polysensitized to assess whether the effect of sensitization on the phenotype was ranked.
RESULTS
Polysensitized patients reported itchy eyes significantly more often (P = .001) and had a higher number of ocular (P = .005), itch-related (P = .036), and total symptoms (P = .007) than monosensitized patients. In addition, polysensitized adults and children more often reported wheeze (P = .015) and throat-clearing (P = .04), respectively. Polysensitization was associated with more burdensome AR based on a visual analog scale (P = .005). Increased sensitization level was reflected in more itchy eyes, a higher number of ocular, itch-related, and total number of symptoms, and disease burden.
CONCLUSION
With an increasing number of sensitizations, patients with AR experience an increased diversity of symptoms. Multimorbidity-related symptoms increase with sensitization rank, suggesting organ-specific thresholds.
PubMed: 38679157
DOI: 10.1016/j.anai.2024.04.026 -
Clinical and Translational Allergy May 2024An innovation to better manage cat-allergic patients utilises anti-Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no...
BACKGROUND
An innovation to better manage cat-allergic patients utilises anti-Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open-label, proof-of-concept study was carried out to approach clinical efficacy of the cat food in cat-allergic patients.
METHODS
After a baseline evaluation, the cats ate only the cat food for the following 4 months. Daily evaluation of efficacy was performed for 2 weeks at baseline and after 1, 2 and 3 months of intervention for periods of 2 weeks. The MASK-air app was used daily to assess symptoms, work productivity and medications.
RESULTS
Of the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK-air data at all 3 evaluation periods. The primary end point (visual analogue scale [VAS] for global allergy symptoms) was significantly improved (p < 0.0001). All symptoms (VAS nose, eye, and asthma), VAS work and the combined symptom-medication score significantly improved after 1 month. The percentage of uncontrolled days (VAS>20/100) decreased from 64% at baseline to 35% at 1 month (p < 0.0001) and 14% at 3 months. A sensitivity analysis in patients with uncontrolled disease at baseline found similar results.
DISCUSSION
A cat diet containing anti-Fel d 1 antibodies was able to (i) show decreased allergic symptoms and related outcomes, (ii) inform the design and feasibility of future studies with a control arm and (iii) estimate the sample size of the study.
STUDY REGISTRATION NUMBER
clinicaltrials.gov: NCT05656482.
PubMed: 38676659
DOI: 10.1002/clt2.12353 -
Scientific Reports Apr 2024Allergic conjunctivitis (AC) is the most common form of allergic eye disease and an increasingly prevalent condition. Topical eye drop treatments are the usual approach... (Comparative Study)
Comparative Study
Allergic conjunctivitis (AC) is the most common form of allergic eye disease and an increasingly prevalent condition. Topical eye drop treatments are the usual approach for managing AC, although their impact on the ocular surface is not frequently investigated. The aim of this study was to perform a comparative physicochemical characterization, and in vitro biological evaluations in primary conjunctival and corneal epithelial cells of the new multidose preservative-free bilastine 0.6% and main commercially available eye drops. MTT assay was used to measure cell viability; oxidative stress was analyzed with a ROS-sensitive probe; and apoptosis was evaluated monitoring caspase 3/7 activation. Differences in pH value, osmolarity, viscosity and phosphate levels were identified. Among all formulations, bilastine exhibited pH, osmolarity and viscosity values closer to tear film (7.4, 300 mOsm/l and ~ 1.5-10 mPa·s, respectively), and was the only phosphates-free solution. Single-dose ketotifen did not induce ROS production, and single-dose azelastine and bilastine only induced a mild increase. Bilastine and single-dose ketotifen and azelastine showed high survival rates attributable to the absence of preservative in its formulation, not inducing caspase-3/7-mediated apoptosis after 24 h. Our findings support the use of the new bilastine 0.6% for treating patients with AC to preserve and maintain the integrity of the ocular surface.
Topics: Ophthalmic Solutions; Humans; Preservatives, Pharmaceutical; Cell Survival; Benzimidazoles; Caspase 3; Apoptosis; Piperidines; Oxidative Stress; Epithelial Cells; Conjunctiva; Caspase 7; Reactive Oxygen Species; Conjunctivitis, Allergic; Phthalazines; Osmolar Concentration; Epithelium, Corneal; Cells, Cultured; Viscosity
PubMed: 38671063
DOI: 10.1038/s41598-024-59190-5 -
Clinical and Experimental Allergy :... Apr 2024The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions.
BACKGROUND
The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions.
OBJECTIVE
We aimed to assess predictive factors of the EAR and LAR and to evaluate the relation between rhinitis, conjunctivitis and asthma induced by cat allergen exposure in an environmental exposure chamber (EEC).
METHODS
Data from two cohort studies involving asthmatic patients with cat allergy who performed a cat allergen exposure challenge in ALYATEC EEC were analysed. Spirometry, visual analogue scale (VAS) for asthma, VAS for rhinitis, Total Nasal Symptoms Score, Total Ocular Symptoms Score (TOSS), Rhinoconjunctivitis Total Symptoms Score and Abelson score were used to assess asthma, rhinitis and conjunctivitis during and after exposure.
RESULTS
An EAR occurred in 65.1% of patients, 32.1% of whom had a LAR. The diameter of the prick test to cat allergens and non-specific bronchial hypersensitivity level were independent risk factors for EAR (p < .05). No independent risk factors for LAR were identified. Rhinoconjunctivitis severity during exposure correlated with the asthma VAS during EAR and LAR (p < .05). Allergen exposure time needed to trigger an EAR correlated with the Abelson score during exposure (p < .05). The asthma VAS and TOSS during exposure correlated with faster LAR occurrence (p < .05).
CONCLUSION
Prick test size and non-specific bronchial hypersensitivity level were confirmed as independent predictive factors of EAR during allergen exposure in an EEC. This study demonstrated the relation between the severity of rhinitis, conjunctivitis and asthma induced by allergen exposure for both EAR and LAR.
PubMed: 38660824
DOI: 10.1111/cea.14485 -
Arquivos Brasileiros de Oftalmologia 2024The prevalence of ocular allergy varies according to the population and location of the study. Severe forms of ocular allergy are associated with compromised quality of...
Translation, adaptation, and psychometric properties of the Brazilian-Portuguese version of the Quality of Life in Children with Vernal Keratoconjunctivitis questionnaire.
PURPOSE
The prevalence of ocular allergy varies according to the population and location of the study. Severe forms of ocular allergy are associated with compromised quality of life. In this study, we aimed to evaluate the application of the Brazilian-Portuguese version of the Quality of Life in Children with Keratoconjunctivitis questionnaire to children and adolescents with different subtypes of allergic conjunctivitis.
METHOD
A total of 48 patients (aged 5-12 years) with allergic conjunctivitis were included in this study. They were enrolled and monitored at a specialized center. After the clinical appointment, the children responded to the questionnaire on two occasions at an interval of 30 days. Individual scores (ranging from 0 to 3) of the 16 items were added.
RESULTS
The Brazilian-Portuguese version of the Quality of Life in Children with Keratoconjunctivitis questionnaire demonstrated good translation, adaptation, and intellectual properties, with substantial internal consistency (Cronbach's α coefficient = 0.702). There was no significant difference between the responses of the two interviews, revealing good reproducibility. The moderate/severe forms of allergic conjunctivitis had significantly higher quality of life scores (indicating a poorer quality of life) than the mild forms.
CONCLUSIONS
The Brazilian-Portuguese version of the Quality of Life in Children with Keratoconjunctivitis proved to be quick, reliable, and reproducible for assessing the quality of life in children with allergic conjunctivitis. However, its ability to detect changes resulting from symptom aggravation or treatment needs to be further evaluated.
Topics: Humans; Quality of Life; Child; Conjunctivitis, Allergic; Brazil; Surveys and Questionnaires; Male; Female; Child, Preschool; Translations; Reproducibility of Results; Psychometrics; Language; Cultural Characteristics; Severity of Illness Index
PubMed: 38656024
DOI: 10.5935/0004-2749.2023-0054 -
Revue Des Maladies Respiratoires May 2024Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the... (Review)
Review
INTRODUCTION
Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the development of biomedicines, of which there are currently five available in France, with a safety profile that appears favorable but remains uncertain due to a lack of real-life experience with these new molecules.
STATE OF KNOWLEDGE
Although relatively benign, the adverse effects of biologics are diverse. Headache, joint pain, skin reactions at the injection site, fever and asthenia are commonly observed during the different treatments. Ophthalmological complications seem restricted to dupilumab, with numerous cases of keratitis and conjunctivitis in patients with atopic dermatitis. Several respiratory complications have also been observed, essentially consisting in pharyngitis and other upper respiratory infections. Hypereosinophilia may occur, mainly with dupilumab, requiring investigation of systemic repercussions or vasculitis. Allergic reactions are uncommon but require careful monitoring during initial injections.
CONCLUSION
Biologics for severe asthma are recent drugs with a favorable safety profile, but with little real-life experience, justifying increased vigilance by prescribing physicians.
Topics: Humans; Asthma; Biological Products; Anti-Asthmatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Omalizumab; France
PubMed: 38653607
DOI: 10.1016/j.rmr.2024.04.001 -
The Journal of Allergy and Clinical... Jun 2024Chronic allergic and nonallergic rhinitis are common phenotypes of a highly prevalent disorder of the upper airways, often associated with asthma. Clinical data,... (Review)
Review
Chronic allergic and nonallergic rhinitis are common phenotypes of a highly prevalent disorder of the upper airways, often associated with asthma. Clinical data, epidemiologic studies, and mHealth-based and genomic approaches indicate the existence of 2 distinct diseases: rhinitis alone and rhinitis + asthma, which may be allergic or less often nonallergic. Both disease phenotypes need to be further characterized, because allergic conjunctivitis, food allergy, and atopic dermatitis, often present in patients with allergic rhinitis, may be considered as independent multimorbidities. Thus, the concept "multimorbid allergic disease" is more appropriate than "one-airway-one-disease." In a meta-analysis, atopic dermatitis was strongly associated with allergic and nonallergic rhinitis, but not with rhinitis and asthma. Asthma alone may also be associated with non-type 2 mechanisms. The distinction between rhinitis alone and rhinitis and asthma was found in all the 12 countries studied using an mHealth app (MASK-air) in Europe and Latin America. These data indicate that the distinction between the 2 diseases is independent of allergen exposure..
Topics: Humans; Phenotype; Asthma; Rhinitis; Multimorbidity; Rhinitis, Allergic; Dermatitis, Atopic
PubMed: 38641129
DOI: 10.1016/j.jaip.2024.04.013 -
Biochemical Genetics Apr 2024In the present study, our aim was to explore the role of MUC4 in IL-4-stimulated conjunctival epithelial cells and the underlying mechanisms. Human recombinant IL-4 was...
In the present study, our aim was to explore the role of MUC4 in IL-4-stimulated conjunctival epithelial cells and the underlying mechanisms. Human recombinant IL-4 was employed in human conjunctival epithelial cells (HConEpic) cells, and MUC4 shRNA (sh-MUC4) was constructed to explore the functional role of MUC4. The protein level of MUC4, O-GlcNAc transferase (OGT), O-GlcNAc hydrolase (OGA), zonula occludens 1 (ZO-1), gap junction protein beta 2 (GJB2), claudin-8 (CLDN8), and E-cadherin were detected by Western blot in HConEpic cells, the interaction between MUC4 and OGT/OGA was assessed by co-immunoprecipitation (IP) and Western blot in 293T cells. Our results showed that IL-4 significantly up-regulated MUC4 and OGT protein levels in HConEpic cells, while down-regulated OGA protein level. Also, IL-4 down-regulated ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, while which was markedly reversed by sh-MUC4. Additionally, OGT inhibitor significantly reduced MUC4 protein level, and elevated ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, while OGA inhibitor resulted in the opposite results. Furthermore, in addition to the interaction between OGT/OGA and MUC4, Co-IP and Western blot also revealed the alteration of MUC4 O-GlcNAcylation in 293T cells treated with OGT/OGA inhibitor. Above findings suggested that OGT/OGA inhibitor regulated MUC4 protein level by affecting MUC4 O-GlcNAcylation to regulate ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, which was achieved via inhibiting the interaction between OGT/OGA and MUC4. This study may provide a better understanding of the pathogenesis of allergic conjunctivitis (AC).
PubMed: 38627316
DOI: 10.1007/s10528-024-10791-9 -
The World Allergy Organization Journal Apr 2024The COVID-19 pandemic brought unprecedented global disruption to both healthcare providers and patients with respiratory allergies. There are limited real-life data on...
BACKGROUND
The COVID-19 pandemic brought unprecedented global disruption to both healthcare providers and patients with respiratory allergies. There are limited real-life data on the impact of the COVID-19 pandemic on the risk perception of patients with allergy treated with allergen immunotherapy (AIT).
OBJECTIVE
To understand the risk perception of allergic patients treated with sublingual immunotherapy (SLIT) before and during the pandemic, and their attitudes towards COVID-19 infection and vaccination.
METHODS
This was a non-interventional, cross-sectional survey conducted from October to November 2021 in France. Adult patients, who had been prescribed and had received a Stallergenes SLIT (liquid or liquid and tablets) before the pandemic (from August 1, 2018 to March 10, 2020) and during the pandemic (from March 11, 2020 to August 31, 2021), were identified from the Stallergenes named-patient products (NPP) database. Patients completed an online questionnaire. Data were analyzed descriptively.
RESULTS
A total of 5258 patients from all over France completed the questionnaire. Mean (±SD) age of the respondents was 39.3 (±13.0) years and 66.9% were female. Some of them (11.8%) were obese (BMI >30 kg/m). Main allergic diseases were rhinitis (80.0% of patients) with or without conjunctivitis, and asthma (39.0%). More than half of the patients experienced moderate to severe (58.0%) and persistent allergic rhinitis profile (70.4%). Most patients were poly-allergic (72.7%), mostly to house dust mites (61.9%), grass pollens (61.5%), tree pollens (57.8%), and cat dander (37.2%). Only 14.1% of patients experienced an aggravation of their allergy symptoms during lockdown and 14.8% were infected with COVID-19, with hospitalization required for 1.8%. Only 3.1% of patients reported their SLIT initiation as being postponed due to the pandemic. SLIT was changed, temporarily interrupted or permanently discontinued during the pandemic in 21.9% of patients. Changes mainly concerned the maintenance dose for SLIT-liquid (63.2%). SLIT modification was due to COVID-19 infection in only 4.2%. Most patients did not feel vulnerable (53.1%), anxious (55.2%), at risk to present severe symptoms of COVID-19 (77.1%), or at risk to transmit coronavirus (80.4%). However, greater anxiety was reported in patients with allergic asthma (33.6%) or other respiratory disorders (50.4%). Patients who felt vulnerable partly assigned their vulnerability to their allergic disease (59.3%). Suffering from an allergic disease did not make patients feel more vulnerable to side effects of COVID-19 vaccine for 79.6% of them.
CONCLUSION
Overall, most patients with allergy and under SLIT were not strongly concerned by the COVID-19 infection. SLIT did not have a negative impact on the COVID-19 symptoms.
PubMed: 38623320
DOI: 10.1016/j.waojou.2024.100902