Kyung‐Ha Lee

ABSTRACT Probiotics offer various health benefits. Lactobacillus plantarum has been used for decades to enhance human intestinal mucosal immunity and improve skin barrier integrity. Extracellular vesicles (EVs) derived from eukaryotic or prokaryotic cells have been recognized as efficient carriers for delivery of biomolecules to recipient cells, and to efficiently regulate human pathophysiology. However, the mechanism underlying the beneficial effects of probiotic bacteria‐derived EVs on human skin is unclear. Herein, we investigated how L. plantarum ‐derived EVs (LEVs) exert beneficial effects on human skin by examining the effect of LEVs on cutaneous immunity, particularly on macrophage polarization. LEVs promoted differentiation of human monocytic THP1 cells towards an anti‐inflammatory M2 phenotype, especially M2b, by inducing biased expression of cell‐surface markers and cytokines associated with M2 macrophages. Pre‐ or post‐treatment with LEVs under inflammatory M1 macrophage‐favouring conditions, induced by LPS and interferon‐γ, inhibited M1‐associated surface marker, HLA‐DRα expression. Moreover, LEV treatment significantly induced expression of macrophage‐characteristic cytokines, IL‐1β, GM‐CSF and the representative anti‐inflammatory cytokine, IL‐10, in human skin organ cultures. Hence, LEVs can trigger M2 macrophage polarization in vitro , and induce an anti‐inflammatory phenomenon in the human skin, and may be a potent anti‐inflammatory strategy to alleviate hyperinflammatory skin conditions.

Circadian mRNA oscillations are the main feature of core clock genes. Among them, period 2 is a key component in negative-feedback regulation, showing robust diurnal oscillations. Moreover, period 2 has been found to have a physiological role in the cell cycle or the tumor suppression. The present study reports that 3'-untranslated region (UTR)-dependent mRNA decay is involved in the regulation of circadian oscillation of period 2 mRNA. Within the mper2 3'UTR, both the CU-rich region and polypyrimidine tract-binding protein (PTB) are more responsible for mRNA stability and degradation kinetics than are other factors. Depletion of PTB with RNAi results in mper2 mRNA stabilization. During the circadian oscillations of mper2, cytoplasmic PTB showed a reciprocal expression profile compared with mper2 mRNA and its peak amplitude was increased when PTB was depleted. This report on the regulation of mper2 proposes that post-transcriptional mRNA decay mediated by PTB is a fine-tuned regulatory mechanism that includes dampening-down effects during circadian mRNA oscillations.

Reaction-based fluorescent probes for monoamine oxidases A and B are developed based on a new two-photon absorbing compound and its precursor. The probes show turn-on fluorescence response to the enzymes owing to the two-photon absorbing compound produced by the enzymatic activity, as monitored by one- as well as two-photon microscopy for the first time.