Conectar
by Aditya Sri Listyoko, Ryota Okazaki, Tomoya Harada, Genki Inui, Hiroki Kohno, Miyu Nishigami, Miki Takata, Masato Morita, Akira Yamasaki
BackgroundThe interaction between viral components and type 1 or type 2 cytokines during asthma exacerbations in the airway epithelium may contribute to worsening inflammation. However, these interactions in the small airway epithelium—particularly those involving alarmins (TSLP, IL-25, and IL-33) and IL-8—remain unclear. Dupilumab, a biologic agent used in severe asthma, blocks IL-4 receptor alpha (IL-4Rα) and may offer therapeutic benefits in virus-induced asthma exacerbations. In this study, we evaluate the effects of double-stranded RNA (dsRNA), in combination with various cytokines and dupilumab, on the Human Small Airway Epithelial Cells (HSAECs) line.
MethodsPrimary HSAECs were preincubated with dsRNA to induce the gene and protein expression of alarmins and IL-8. To evaluate the effects of cytokines on dsRNA-induced alarmin and IL-8 expression, various type 1 and type 2 cytokines were co-stimulated with dsRNA. Dupilumab was used as a pretreatment prior to co-stimulation with dsRNA and IL-4 or IL-13. Gene expression of TSLP, IL-25, IL-33, and IL-8 was assessed by quantitative PCR, and protein expression was evaluated by Western Blotting.
ResultsdsRNA significantly increased the expression of TSLP and IL-8. IL-4 and IL-13 further enhanced dsRNA-induced TSLP and IL-8 gene and protein expression. In contrast, TNF-α reduced dsRNA-induced TSLP expression but enhanced IL-8 gene and protein expression. Dupilumab attenuated the expression of TSLP and IL-8 induced by co-stimulation with dsRNA and IL-4 or IL-13 in HSAECs.
ConclusionIn the microenvironment of small airway epithelial cells, particularly during viral infections, the presence of IL-4 or IL-13 may enhance the expression of TSLP and IL-8. Dupilumab attenuates this expression, potentially offering additional benefits in the treatment of asthma, especially during virus-induced asthma exacerbations.
The intestinal microbiota of people with Parkinson’s disease (PwP) differs significantly from that of healthy individuals. Given that altered microbiota may play a role in the pathogenesis of Parkinson’s disease, faecal microbiota transplantation (FMT) has been proposed as a potential therapeutic approach. However, the efficacy of FMT in improving motor symptoms in PwP has been inconclusive in some pilot randomised controlled trials (RCT). Previous RCTs on PwP employed simple FMT, but our modified approach—pretreatment with antibiotics before FMT (A-FMT)—has been shown to improve the engraftment rate of given species and the beneficial effects of FMT. This study aims to evaluate the efficacy and safety of A-FMT for PwP, particularly in those with motor fluctuations.
This study is a randomised, double-blind, placebo-controlled, parallel-group study with an 8-week observation period following a single A-FMT. Thirty clinically established PwP with prominent motor fluctuation episodes will be randomised 1:1 to FMT or placebo. Participants in both groups will receive antibiotic treatment prior to colonoscopy for FMT or placebo treatment. Primary and secondary endpoints will include subjective and objective evaluations of motor and non-motor symptoms and will be evaluated before and after antibiotic treatment and at 4 and 8 weeks after the procedure. Exploratory endpoints will include blood and faecal sample analyses, advanced brain MRI and pharmacokinetic assessment of levodopa concentrations during a levodopa challenge test.
This study has been approved by the ethical committee of Juntendo University in August 2024 (J24-005) and will be conducted in accordance with the Declaration of Helsinki, the Japan Ministry of Health, Labour and Welfare Clinical Trials Act and related laws and regulations. All patient data will be anonymised to protect privacy and used solely for study purposes. Results will be published in academic journals and presented at conferences.
jRCTs031240344.
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