Ad-HGF(The First Affiliated Hospital with Nanjing Medical University)

This study aims to explore the potential mechanism of Achyranthoside D (AD) in improving intervertebral disc (IVD) degeneration (IDD).

The IDD model of SD rats and nucleus pulposus cells (NPCs) was established by lumbar cone annulus puncture and tert-butyl peroxide, respectively. Cell proliferation was detected by CCK8 assay. Apoptosis was detected by flow cytometry and TUNEL staining. IVD tissue injury was observed by HE staining. Alcian blue staining observed the glycoprotein secretion in IVD. Monodansylcadaverin (MDC) staining was used to detect the formation of autophagosomes. The LC3 expression was tested by immunofluorescence. The type II collagen, aggrecan and MMP3 expression were detected by ELISA. RT-qPCR was used to detect the Casp 3, Bax, Bcl2, Acan, Col2a1 and Mmp3 expression. The LC3, P62, type II collagen, aggrecan, Beclin1, Akt, MMP3, p-mTOR, PI3K, mTOR, p-PI3K and p-Akt expression were analyzed by western blot.

The IVD tissue damage and apoptosis occurred in the Model group, and the glycoprotein secretion decreased. Compared with Model group, AD-H group alleviated the injury of IVD tissue, inhibited the apoptosis of cells, and increased the secretion of glycoprotein. 40 μg/mL AD restored the proliferation activity of NPCs. Compared to the Normal group, the NPCs apoptosis increased, the Collagen II, aggrecan and Bcl2 expressions were significantly decreased, the MMP3, Bax and Casp 3 expression were significantly increased, and the LC-3 II/I expression in IVD tissues were increased significantly in Model group, all of which was reversed in AD group. AD promoted the p-Akt, p-PI3K, p-mTOR, LC-3 II/I and Beclin1 expression, inhibited the P62 expression to alleviate the damage of nucleus pulporeus cells and the degeneration of IVD.

AD improved IDD by affecting the PI3K/Akt/mTOR pathway and autophagy.

The nonlesional skin of children with atopic dermatitis (AD) with peanut allergy (PA) is associated with increased transepidermal water loss; low urocanic acid (UCA) and pyrrolidone carboxylic acid (PCA), both of which are filaggrin breakdown products; and a reduced ratio of esterified ω-hydroxy fatty acid sphingosine ceramides (EOS-CERs) to nonhydroxy fatty acid sphingosine ceramides (NS-CERs) in the skin. The skin barrier of subjects with PA without AD (AD^-PA⁺) has not been studied.

Our aim was to explore whether AD^-PA⁺ is associated with skin barrier abnormalities.

A total of 33 participants were enrolled, including 13 AD^-PA⁺, 9 AD⁺PA⁺, and 11 nonatopic (NA) participants.

The PCA content in the stratum corneum of AD^-PA⁺ subjects was significantly reduced versus that in NA subjects (median level, 67 vs 97 μg/mg protein [P = .028]). The ratio between cis- and trans-UCA decreased significantly from being highest in the NA group (1.62) to lowest in AD⁺PA⁺ group (0.07 [P < .001 vs in the NA group; P = .006 vs in the AD^-PA⁺ group]), with the AD^-PA⁺ group having an intermediate cis/trans-UCA ratio (1.17 [P = .024 vs in the NA group]). The TEWL in AD^-PA⁺ subjects did not differ from that in the group with NA skin. Interestingly, AD^-PA⁺ subjects had an increased EOS/NS-CER ratio versus that in the group of subjects with NA skin (1.9 vs 1.3 [P = .008]), whereas the AD⁺PA⁺ group had a decreased proportion of EOS-CERs (0.8 [P = .001] vs in the AD^-PA⁺ group).

Our data demonstrate that irrespective of AD, PA is associated with decreased skin cis-UCA and PCA content. An increase in skin EOS-CER/NS-CER ratio separates the AD^-PA⁺ group from the AD⁺PA⁺ and NA groups.