Butler Lillelund (hockeyweight0)

RNA‑seq and western blotting demonstrated that the PI3K/mTOR/HIF1α signaling pathway was activated by PDCC4, and a selective PI3K inhibitor reversed the protective function of PDCC4 on TNF‑α stimulated HUVECs. Additionally, PDCC4 alleviated hypertension, histopathological changes of placenta and kidney and the expression levels of endothelial injury markers and inflammatory cytokines induced by LPS in rats. These results suggested that PDCC4 relieved endothelial dysfunction in PE via PI3K/mTOR/HIF1α signaling pathway and may be a potential therapy for PE.Osteoarthritis (OA) is a highly prevalent disease worldwide that causes disability and diminishes the quality of life of affected individuals. The disease is characterized by cartilage destruction, increased inflammatory responses and cholesterol metabolic disorder. Scutellarin is the major active ingredient extracted from Erigeron breviscapus, and it has been demonstrated to possess various pharmacological functions in the treatment of the disease. However, its effects on OA are complex. The present study investigated whether scutellarin can mediate the release of inflammatory cytokines, the expression of collagen- and cholesterol-related proteins, and regulate the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in a cell model of OA. Interleukin (IL)-1β was used to stimulate OA in SW1353 cells in vitro. The primary methods used were ELISA and western blotting, which were carried out to examine the effects of scutellarin on the cell model of OA. It was found that scutellarin increased the expression of collagen II and SRY-box 9, whereas it suppressed the expression of matrix metalloproteinase 13. In addition, scutellarin downregulated the expression levels of cholesterol 25-hydroxylase and cytochrome P450 family 7 subfamily B polypeptide 1, but upregulated the expression of apolipoprotein A-1 and adenosine triphosphate-binding cassette transporter A1. The IL-1β-induced increase in the expression of IL-6 was decreased by treatment with scutellarin; however, scutellarin did not alter the expression of C-reactive protein and tumor necrosis factor-α. The protein expression levels of AKT, phosphorylated (p)-AKT, mTOR and p-mTOR in the PI3K/AKT/mTOR signaling pathway were decreased in the IL-1β-induced SW1353 cells following scutellarin treatment. Overall, the findings of the present study demonstrated that scutellarin regulated OA in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway.Autophagy plays a dual role in the responses to the gut microflora. The present study aimed to examine the effects of Lactobacillus rhamnosus (L. rhamnosus) on Fusobacterium nucleatum (F. nucleatum)‑induced intestinal dysfunction and to elucidate the underlying mechanisms, with particular focus on autophagy. Inflammatory models were established by treatment with L. rhamnosus following F. nucleatum intervention using cells or a mouse model of dextran sulfate sodium (DSS)‑induced acute colitis. Autophagosomes were visualized by confocal microscopy following transfection with a tandem GFP‑mCherry‑LC3 construct and also by transmission electron microscopy. Autophagy‑associated protein levels were examined by western blot analysis and immunohistochemistry. It was observed that F. nucleatum induced the production of pro‑inflammatory cytokines in Caco‑2 cells and aggravated DSS‑induced acute colitis. The autophagic flux was impaired following infection with F. nucleatum. L. rhamnosus treatment attenuated the inflammation induced by F. nucleatum infection and effectively recovered the impaired autophagic flux. In addition, the production of pro‑inflammatory cytokines induced by F. nucleatum was enhanced with autophagy inhibitors or the RNA interference of autophagy‑related gene 16 like 1 (Atg16L1) in Caco‑2 cells. Notably, this inhibition of autophagy weakened the effects of L. rhamnosus. Finally, the PI3K/AKT/mTOR pathway was found to be involved in this pro