No abstract

Sophoraflavanone G (SG) was isolated from Sophora flavescens. Previously, we have found that SG is able to suppress the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophages. This study aimed to evaluate the effects of SG on apoptosis, and explore its molecular mechanism in human leukemia HL-60 cells. HL-60 cells were treated with various concentrations of SG (3-30 [Formula: see text]M). The viability of the HL-60 cells was assessed using the MTT method, and the nuclear condensation indicative of apoptosis was observed by DAPI fluorescence staining. In addition, apoptotic signal proteins were examined using Western blotting. The results showed that apoptosis, including DNA fragmentation and nuclear condensation, increased significantly in SG-treated HL-60 cells. SG activated caspase-3 and caspase-9, and downregulated Bcl-2 and Bcl-xL. SG also upregulated Bax and released cytochrome c from the mitochondria into the cytoplasm, enabling apoptosis via the mitochondrially-mediated "intrinsic" pathway. Additionally, SG was able to cleave poly (ADP-ribose) polymerase 1 and activate mitogen-activated protein kinase (MAPK) pathways. These results suggest that SG might increase the effect of apoptosis on HL-60 cells through caspase-3 activation, mitochondrial-mediated pathways, and the MAPK pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor‐beta (TGF‐β) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin‐22 (IL‐22) in the pathogenesis of IPF by regulating the TGF‐β pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL‐22R knock out (IL‐22RA1−/−) and IL‐22 supplementation mouse models were used to determine if IL‐22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL‐22 and/or TGF‐β1. In a clinical cohort, the expression level of IL‐22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL‐22 expression was associated with poorer pulmonary function. IL‐22R−/− mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL‐22 augmentation by intranasal instillation of recombinant IL‐22 repressed inflammation and fibrotic phenotype. In vitro, IL‐22 treatment repressed TGF‐β1 induced gene markers representing epithelial‐mesenchymal‐transition and fibroblast‐myofibroblast‐transition, likely via the inhibition of TGF‐β receptor expression and subsequent Smad2/3 activation. IL‐22 appears to be protective against pulmonary fibrosis by inhibiting TGF‐β1 signaling, and IL‐22 augmentation may be a promising approach to treat IPF.

Background Guided endodontics is a successful technique that has been gradually applied to endodontic therapy in recent years without being affected by the operator’s experience. However, the guided bur produces excessive heat during continuous rotation and friction with root canal walls, it is not clear whether the degree of temperature increase may lead to the periodontal ligament and alveolar bone damage. Methods A total of 58 teeth were used, of which 40 teeth were not grouped, all used to evaluate the accuracy. 40 single-rooted premolars were scanned using CBCT and an intra-oral scanner, and 3D-printed guided plates were made with the pre-designed access. A custom-made guided bur was used to prepare the access cavities. The postoperative CBCT data and pre-designed pathways were matched to evaluate the deviation between the planned and virtual paths. The other 18 teeth were randomly divided into three groups (ET20 and ProTaper F3 as the control group, guided endodontics as the test group), with 6 teeth in each group. The temperature changes on the root surfaces were inspected with a thermocouple thermometer. Results The average deviation on the tip and the base of the bur was 0.30 mm and 0.28 mm (mesial/distal), and 0.28 mm and 0.25 mm (buccal/lingual). The average angle deviation was 3.62°. The mean root surface temperature rise of the guided endodontics group was the lowest (5.07 °C) (P < 0.05). Conclusions The access cavity preparation performed with guided endodontics has feasible accuracy and low-temperature rise on the root surfaces. Due to the limitations of the study, whether it has high reliability and safety in clinical applications needs to be further studied in vivo.