Search

Triggering receptor expressed on myeloid cells‐1 (TREM‐1) exists in two forms: a transmembrane form and a soluble form (sTREM‐1). The levels of sTREM‐1 are elevated in supernatants of activated HSCs. However, the role of sTREM‐1 in HSC activation and liver fibrosis remains undefined. Previous studies have primarily focused on the transmembrane form of TREM‐1; we innovatively observed the function of sTREM‐1 as a ligand in liver fibrosis and screened its receptor. Here, recombinant sTREM‐1 was used as a stimulator which induced HSC activation and further aggravated liver fibrosis. Then, screening for sTREM‐1 interacting membrane receptors was performed using pull‐down assay followed by mass spectrometry, and the membrane receptor roundabout guidance receptor 2 (Robo2) was identified as a candidate receptor for sTREM‐1. The interaction between sTREM‐1 and Robo2 was verified by pull‐down and immunofluorescence. The role of Robo2 on sTREM‐1‐induced HSC activation and its downstream signal pathways was assessed by knockdown of Robo2 in LX‐2 cells. Furthermore, HSC‐specific knockdown of Robo2 was achieved in a mouse model of liver fibrosis by using a recombinant adeno‐associated virus (AAV) vector to confirm the role of the receptor, and we proved that Robo2 knockdown inhibited the activation of HSC and liver fibrosis, which also led to the inactivation of Smad2/3 and PI3K/Akt pathways in sTREM‐1‐induced HSC activation and liver fibrosis. In conclusion, sTREM‐1 acts as a new ligand of Robo2; the binding of sTREM‐1 to Robo2 initiates the activation of the downstream Smad2/3 and PI3K/Akt signalling pathways, thereby promoting HSC activation and liver fibrosis.

OBJECTIVES The aim of this study was to identify whether arsenic (As) exposure could induce hippocampal neural apoptosis in vivo. METHODS Sixty-four mice were randomly divided into 4 groups of 16 each. Group 1 orally received drinking water alone as a control. Groups 2-4 were given arsenic trioxide (As2O3) orally at the doses of 1 ppm, 2 ppm and 4 ppm, respectively. All the treatments continued for 60 days. Morphological changes in the hippocampus were observed by HE staining. Apoptosis in the hippocampus was examined by TUNEL assay and transmission electron microscopy. The expression levels of Bcl-2 and Bax genes and their proteins in the hippocampus were determined by real-time PCR and Western blotting. The activity of caspase-3 was determined by spectrophotometry. RESULTS Abnormal histopathological changes and apoptosis were found in the hippocampus of As-exposed mice. The expressions of the Bcl-2 gene and its protein in the hippocampus of As-exposed mice were significantly lower than those in the control group (p

Application of the reaction conditions to oxadiazole, benzimidazole and imidazole derivatives fails to furnish amidated products.

A new polyhydroxylated sterol, named sardisterol, was isolated from the soft coral Sarcophyton digitatum Moser. Its structure was determined as (22R, 24ξ)-methylcholest-5-en-3β, 22, 25, 28-tetraol-3-acetate on the basis of spectroscopic methods.