HAS1 x HAS2

Severe prenatal maternal stress is a risk factor for schizophrenia in offspring. Since parvalbumin-containing GABAergic interneuron function in the cortex and hippocampus is compromised in schizophrenia, and perineuronal nets (PNNs) facilitate the functioning of these cells, we tested the hypothesis that glucocorticoids, as stress mediators that can access the foetal compartment, might influence the expression of PNN component genes. In cultured mouse cortical neurons, we detected effects of hydrocortisone on many PNN component genes, via diverse mechanisms. A rapid (< 4 h), glucocorticoid receptor (GR)-mediated suppression of neurocan and hyaluronan synthase ( Has ) 1 and 3 mRNAs was observed at 7 days in vitro (DIV), whereas at 14 DIV, brevican and versican expression was reduced by hydrocortisone without GR involvement, while GR inhibition elevated Has1 and Has2 mRNA levels and suppressed aggrecan mRNA levels. Tenascin R expression was rapidly suppressed by hydrocortisone at 7 DIV but not at 14. At 21 DIV, PNN component gene expression had become insensitive to hydrocortisone, although parvalbumin expression was reduced after 24 h but not 4 h exposure. Additionally, effects on protein levels were observed that were sometimes consistent with the mRNA changes (e.g. Has3, Gad1) and sometimes unrelated to them (e.g. elevated TnR levels at 7 DIV after glucocorticoid receptor antagonism). We found that hydrocortisone could directly inhibit proteasome activity. As expected from these results, the overall structure of the PNN was compromised by hydrocortisone exposure, with the length of the proximal dendrite covered by PNN being reduced. Overall, the data demonstrate a complex and profound, but developmental stage-dependent, regulation of PNN component gene expression by glucocorticoids. This may contribute to the action of severe prenatal or perinatal stress to increase schizophrenia risk.

Electronic (e)-cigarette and e-liquid exposure have been linked to vocal fold inflammation and dysphonia, yet no targeted non-surgical therapies currently exist. Hyaluronan, a key extracellular matrix component essential for vocal fold structure, repair, and function, is known to be dysregulated in inflammatory conditions; however, its metabolic gene response to e-liquid exposure in human vocal fold fibroblasts (hVFFs) remains uncharacterized. Hence, it is critical to understand hyaluronan metabolic gene expression under e-liquid toxicity to develop novel drug discovery strategies for vocal fold inflammation. To avoid confounding effects from thermal degradation and aerosol variability in conventional vapor models, hVFFs were exposed to nicotine-containing unvaporized e-liquid (0.125-1 mg/mL) for 24 h, revealing concentration-dependent changes in cell morphology and viability (p < 0.05). The lethal concentration 50 (LC₅₀) was determined to be 0.437 mg/mL and used for short-term (24 h) and extended (72-96 h) exposures. Extended exposure induced intracellular reactive oxygen species (ROS), inflammation, suppressed collagenolysis, and increased the collagen 1 A: collagen 3 A ratio, suggesting fibrotic remodeling. Short-term exposure downregulated hyaluronan synthases (HAS1, HAS2, HAS3) and catabolic genes (HYAL2, CD44), reducing extracellular hyaluronan levels. In contrast, extended exposure repressed HAS1 and HAS2 while upregulating HAS3, CD44, and HYAL2, indicating enhanced hyaluronan degradation and accumulation of proinflammatory low molecular weight hyaluronan. CD44 silencing reduced IL-8 mRNA expression, confirming its role in hVFF inflammation. These findings provide the first mechanistic insight into unvaporized e-liquid-induced dysregulation of hyaluronan metabolism in hVFFs, offering a foundation for biomarker identification and therapeutic development targeting e-cigarette-associated vocal fold inflammation.

Edible snail extract powder, which is known to hydrate and help heal skin, was evaluated to see if it could protect against skin damage from UVB via oral administration in an SKH‐1 hairless mouse model. Over a period of 117 days, mice were exposed to UVB radiation and given edible snail extract powder to assess its impact on skin health. Toxicity tests confirmed its safety, with no significant changes in body weight, organ weights, or serum markers. Physiological analyses showed that edible snail extract powder significantly improved skin hydration, reduced trans epidermal water loss (TEWL), and inhibited wrinkle formation. Histological examination revealed increased collagen deposition and reduced stratum corneum thickness. At the molecular level, edible snail extract powder restored the expression of hyaluronic acid synthases (HAS1, HAS2, HAS3), collagen‐related genes (Col1a1, Col1a2), and Sod, while suppressing the levels of Mmp‐1, a matrix‐degrading enzyme elevated by UVB exposure. These findings suggest that oral administration of edible snail extract powder might enhance skin barrier function and combat photoaging through antioxidant, anti‐inflammatory, and ECM‐preserving mechanisms. This study highlights its potential as a functional food ingredient for skin health, warranting further investigation into its molecular pathways.