HAS1 x HAS2

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease characterized by inflammation and tissue remodeling, with fibrosis being a predominant and often irreversible feature in type II TAO. While immunosuppressive therapies offer limited efficacy, there remains a critical need to identify effective molecular targets for fibrotic TAO. Circular RNAs (circRNAs) have emerged as key regulators in various diseases, yet their roles in TAO are largely unexplored. In this study, we identified hsa_circ_0007006 as significantly downregulated in fibrotic TAO tissues through high-throughput RNA sequencing. Functional assays in orbital fibroblasts revealed that circ-0007006 suppresses fibrosis by downregulating COL1A1, α-SMA, HAS1, and HAS2, and inhibiting SMAD2/3 phosphorylation. Mechanistically, circ-0007006 functions as a competing endogenous RNA for miR-383-3p, thereby stabilizing HBEGF expression. Rescue experiments showed that exogenous HBEGF alleviates the pro-fibrotic effects induced by circ-0007006 knockdown. These findings identify the circ-0007006/miR-383-3p/HBEGF axis as a novel regulatory pathway in TAO fibrosis and support circ-0007006 as a potential therapeutic target for the fibrotic subtype of TAO.

Human milk oligosaccharides (HMOs) delivered via breastfeeding stimulate Bifidobacterium proliferation in the infant gut, where bacterial adhesion is critical for colonization. This study screened HMOs-utilizing Bifidobacterium strains from infant fecal microbiota and investigated their adhesion mechanisms. In vitro fermentation with lacto-N-triose II (LNT II), 2'-fucosyllactose (2'-FL), and 3'-sialyllactose (3'-SL) showed that 2'-FL significantly increased butyric acid production and suppressed harmful bacteria in two week-old infants. Three Bifidobacterium bifidum strains (B-63, B-67, and B-82) capable of HMOs utilization were identified, carrying conserved HMO-digestion gene clusters including key GH13 and GH20 glycoside hydrolases. Then, the effects of LNT II, 2'-FL, and 3'-SL treatments on adhesion capacity of three B. bifidum strains to Caco-2 intestinal epithelial cells were investigated, and results demonstrated that 2'-FL significantly upregulated hyaluronan synthase 2 (HAS2) and MUC2 expression in strains B-63 and B-67. Furthermore, addition of 2'-FL to fucosyl-inhibited cells selectively upregulated HAS1 protein expression, demonstrating that 2'-FL-mediated fucosylation promotes intestinal epithelial cell adhesion.

Bai-Ju essence (BJE) is a bioactive formulation composed of medicinal plant extracts, utilized in skincare products for its therapeutic potential. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation. This study aimed to evaluate BJE anti-inflammatory and skin-protective effects, and its potential mechanisms in treating AD. The ability of BJE to restore the epidermal barrier was assessed in HaCaT cells. In LPS-induced RAW264.7 cells, the anti-inflammatory potential of BJE was evaluated by measuring NO, IL-6, PGE2, and TNF-α. Western blot analysis was used to assess the regulation of the MAPK pathway. An in vivo AD-like mouse model was established using MC903, and measurements of body weight, ear thickness, and AD symptoms were recorded. Histological analysis quantified mast cell infiltration, while western blot determined FLG, LOR, and ELOVL6 expression. ELISA was used to measure TNF-α, IgE, IL-4, and IL-13 levels. Flow cytometry assessed the effect of BJE on Th cell phenotypes. BJE significantly enhanced skin barrier protein expression (CERS2, LOR, HAS-1, HAS-2, FLG) in HaCaT cells. It significantly reduced the levels of NO, IL-6, PGE2, and TNF-α in LPS-treated RAW264.7, demonstrating its anti-inflammatory potential. Mechanistically, BJE inhibited MAPK activation. BJE decreased ear thickness, improved skin lesions, and relieved AD symptoms in AD-like mice. In addition, BJE effectively suppressed mast cell infiltration and hyperkeratosis. BJE also decreased levels of TNF-α, IgE, IL-4, and IL-13 while increasing LOR, ELOVL6, and FLG expressions. Furthermore, BJE modulated Th1, Th2, and Th17 cell proportions. BJE promoted epidermal barrier repair in HaCaT, suppressed the LPS-induced inflammation in RAW264.7, enhanced the skin barrier integrity in AD-like mice, and exhibited immunomodulatory effects by restoring Th cell balance. These findings highlighted the therapeutic potential of BJE in AD through its dual action of anti-inflammation and skin barrier restoration.