Barrier dysfunction of airway epithelium contributes to the development of allergies, airway hyper-responsiveness and immunological respiratory diseases. Short-chain fatty acids (SCFA) enhance and restore the barrier function of the intestinal epithelium. This study investigated whether acetate, propionate and butyrate enhance the integrity of bronchial epithelial cells. Differentiating human bronchial epithelial cells (16HBE) grown on transwells were exposed to butyrate, propionate and acetate while trans-epithelial electrical resistance was monitored over time. Restorative effects of SCFA were investigated by subsequent incubation of cells with IL-4, IL-13 or house dust mite extract and SCFA. SCFA effects on IL-4-induced cytokine production and the expression of zonula occludens-1 (ZO-1) and Mitogen-activated protein kinases (MAPK) signalling pathways were investigated by ELISA and Western blot assays. Propionate and butyrate enhanced the barrier function of differentiating 16HBE cells and induced complete recovery of the barrier function after exposure to the above-mentioned stimuli. Butyrate decreased IL-4-induced IL-6 production. IL-4 decreased ZO-1 protein expression and induced phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in 16HBE cells, both of which could be restored by SCFA. SCFA showed prophylactic and restorative effects on airway epithelial barrier function, which might be induced by increased ZO-1 expression.

Short-chain fatty acids (e.g., butyrate and propionate) are able to diminish endothelial cell activation. The aim of this study was to investigate whether intracellular IL-33 mediates the effects of butyrate and propionate on TNFα-induced IL-8 production and vascular cell adhesion molecule-1 (VCAM-1) expression. In addition, it was investigated whether regulating NF-κB and MAPK signaling pathways are involved. Intracellular IL-33 was measured in human endothelial cells (HUVECs) pre-incubated for 24 h with butyrate (0.1 mM or 5 mM), propionate (0.3 mM or 10 mM), or trichostatin A (TSA, 0.5 μM) prior to TNFα (1 ng/mL) stimulation (24 h). The effects of butyrate, propionate, and TSA on TNFα-induced IL-8, vascular cell adhesion molecule-1 (VCAM-1), NF-κB, and MAPK signaling pathways in normal HUVECs and IL-33 siRNA (siIL-33)-transfected HUVECs were compared to study the role of IL-33 in the protective effects of butyrate and propionate. Endogenous IL-33 was highly expressed in the perinuclear in HUVECs, which was significantly reduced by TNFα stimulation. The TNFα-induced reduction in IL-33 was prevented by pre-incubation with butyrate or propionate. Butyrate (0.1 mM), propionate (0.3 mM), and TSA inhibited the IL-8 production and activation of NF-κB. Interestingly, this effect was not observed in siIL-33-transfected HUVECs. The effects of butyrate (5 mM), propionate (10 mM), and TSA (0.5 μM) on VCAM-1 expression and activation of MAPK signaling pathways were not affected by siIL-33 transfection. In conclusion, we showed that the inhibitory effects of butyrate and propionate on TNFα-induced IL-8 production were mediated by the HDACs/IL-33/NF-κB pathway, while their effects on VCAM-1 expression might be associated with the HDACs/MAPK signaling pathway, independently of IL-33.

Acute necrotizing encephalopathy (ANE) secondary to influenza infection is characterized by fulminant neurological deterioration and a high mortality rate. The underlying mechanisms remain unclear, and specific treatments are currently lacking. Therefore, understanding the pathogenesis and identifying diagnostic and therapeutic targets for influenza-induced ANE are crucial. Peripheral blood samples were collected from two groups: influenza-infected patients without ANE (mild) and influenza infection with ANE patients (severe). Differentially expressed genes (DEG) were identified through microRNA sequencing analysis, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression levels of the four specific miRNAs were validated using qRT-PCR. In the severe group, 24 genes were up-regulated, and 67 genes were down-regulated compared to the mild group. The expression levels of hsa-miR-1290, hsa-miR-4657, has-miR-1231, and hsa-miR-342-3p were validated by qRT-PCR, and the levels of has-miR-4657 and hsamiR- 342-3p showed significant differences between severe and mild groups. GO analysis demonstrated that the DEGs were predominantly involved in the positive regulation of cellular processes, intracellular anatomical structure, and protein binding. KEGG pathway analysis revealed that DEGs were mainly enriched in calcium signaling pathway and axon guidance. The down-regulated hsa-miR-4657 and hsa-miR-342-3p might be associated with the development of ANE in pediatric patients with influenza by regulation of calcium pathways and axon guidance.

Purpose: The purpose of this study is to analyze clinical characteristics of patients with Kawasaki disease (KD) aged below 1 year and identify risk factors for coronary aneurysm (CA) and its associated prognosis. Methods: A retrospective study enrolling infants (under 1 year of age) with KD admitted to a children’s hospital between January 1, 2012, and August 30, 2024, was conducted. Patients were divided into two groups based on CA presence. Clinical records, including demographics, clinical manifestations, treatments, laboratory parameters, and cardiac ultrasound examination, were collected and analyzed. Results: Of 381 infants with KD, 96 developed CA. Male sex (adjusted odds ratio [aOR] = 1.982, p = 0.04), duration of fever (aOR = 1.143, p = 0.03), illness days of initial intravenous immunoglobulin (IVIG) (aOR = 1.319, p < 0.01), and higher C‐reactive protein (CRP) (aOR = 1.007, p = 0.02) were associated with CA development in infants with KD in multivariable analysis. Specifically, an increase of 10 mg/L in CRP is associated with a 7.2% elevation in risk of CA development. Among patients diagnosed with CA, 30, 42, and 24 had small aneurysm (sAN), medium aneurysm (mAN), and giant aneurysm (gAN), respectively. The complete regression proportion and regression times of sAN, mAN, and gAN were 86.7%, 76.2%, and 33.3% and 3.9 ± 9.2, 12.8 ± 17.2, and 20.7 ± 11.2 months, respectively. Conclusions: CA incidence was higher in infants with KD and was associated with male sex, fever duration, days of initial IVIG, and higher CRP. The ability and time of regression depend on the size of the CA; however, giant CA in infant patients has a greater tendency to regress than those in older patients with KD.