LL-37, a 37-amino acid human-derived antimicrobial peptide, was shown in our earlier clinical study to shorten the negative conversion time of the Omicron BA.5.1.3 variant of SARS-CoV-2. In this work, we investigated the broad mechanism of LL-37 by examining its inhibitory effect on non-enveloped virus Enterovirus 71 (EV71). LL-37 treatment dose-dependently reduced EV71 viral RNA abundance, suppressed virus-encoded protein expression, and decreased infectious titers, acting predominantly at a post-entry stage of the viral life cycle. Transcriptomic analysis revealed that the SH3 and cysteine-rich domain protein (Stac) was uniquely upregulated by LL-37 irrespective of EV71 infection. Short hairpin RNA (shRNA)-mediated Stac silencing significantly enhanced EV71 infection, while Stac overexpression markedly reduced it. Furthermore, we found that LL-37 activates the EGFR–ERK signaling pathway, leading to time-dependent upregulation of Stac expression. These findings uncover a novel host-directed mechanism by which LL-37 combats EV71 infection and suggests a potential therapeutic use of LL-37 against non-enveloped viral disease.

It is well-known that childhood obesity is associated with various adult gastrointestinal diseases, inflammatory bowel disease (IBD) being no exception. However, previous epidemiological observational studies, while reporting a correlation between the 2, have left the question of a causal relationship inconclusive. This study aims to use a 2-sample Mendelian randomization (MR) analysis to assess the causal relationship between childhood obesity and IBD as well as its subtypes (ulcerative colitis [UC] and Crohn disease [CD]). Data on childhood obesity, IBD, and its subtypes (UC and CD) were sourced from IEU OpenGWAS (https://gwas.mrcieu.ac.uk/datasets/ieu-a-1096/) and IIBDGC (https://www.ibdgenetics.org/). The data were analyzed using the inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. The MR analysis indicates no causal relationship between childhood obesity and IBD or its subtypes (UC and CD). The consistency of the results across the IVW, MR-Egger, weighted median, simple mode, and weighted mode methods suggests the reliability of the findings. We found that childhood obesity is not causally related to IBD or its subtypes (UC and CD). This differs from prior studies. The observed discrepancies may be due to common biological or environmental confounding factors.