Natural compound fraxinellone ameliorates intestinal fibrosis in mice via direct intervention of HSP47-collagen interaction in the epithelium.

Intestinal fibrosis is a common complication of inflammatory bowel disease. There is still a lack of effective drugs for the prevention or treatment of intestinal fibrosis. Heat shock protein 47 (HSP47) plays a key role in the development of intestinal fibrosis. In this study we investigated the therapeutic potential and underlying mechanisms of fraxinellone, a degraded limonoid isolated from the root bark of Dictamnus dasycarpus, in the treatment of intestinal fibrosis. Intestinal fibrosis was induced in mice by dextran sodium sulfate (DSS) treatment. DDS-treated mice were administered fraxinellone (7.5, 15, 30 mg·kg-1·d-1, i.g.) for 45 days. We showed that fraxinellone administration dose-dependently alleviated DSS-induced intestinal impairments, and reduced the production of intestinal fibrosis biomarkers such as α-smooth muscle actin (SMA), collagen I, hydroxyproline, fibronectin and laminin, and cytokines such as TGF-ß, TNF-α and IL-ß. We then established in vitro intestinal fibrosis cell models in SW480 and HT-29 cells, and demonstrated that treatment with fraxinellone (3, 10, 30 µM) significantly relieved TGF-ß-induced fibrosis responses by inhibiting the TGF-ß/Smad2/3 signaling pathway. Molecular docking suggested that the fraxinellone might disrupt the interaction between HSP47 and collagen, which was confirmed by coimmunoprecipitation experiments. SPR analysis showed that fraxinellone had a high affinity for HSP47 with a Kd value of 3.542 × 10-5 M. This study provides a new example of HSP47-collagen intervention by a natural compound and has important implications for the clinical treatment of inflammation-induced issue fibrosis.

Clinical analysis on the root fracture of the maxillary first molar.

OBJECTIVES: This study aimed to investigate the common types and directions of root fractures of the maxillary first molar and the influence of root canal treatment on the prevalent sites of root fractures. METHODS: A total of 274 maxillary first molars with root fractures diagnosed via cone beam computed tomography were included. The root fractures of nonendodontically and endodontically treated teeth were identified to be spontaneous and secondary root fractures, respectively. The sites, types, and directions of spontaneous and secondary root fractures were determined. RESULTS: Among the spontaneous root fractures, the proportion of palatal root fractures (56.1%) was higher than those of mesial buccal root fractures (36.1%) and distal buccal root fractures (7.8%). Among the secondary root fractures, the proportion of mesial buccal root fractures (52.7%) was higher than those of palatal root fractures (36.5%) and distal buccal root fractures (10.8%). The distribution of predominant fracture sites was statistically significant (P<0.05), and vertical root fracture was the most common type. Palatal and buccal roots were commonly fractured at the mesiodistal and buccal-palatal directions, respectively. CONCLUSIONS: This study provided an epidemiological basis for the clinical features of root fractures of the maxillary first molar. During the dia-gnosis and treatment of the maxillary first molar, the possibility of palatal root fractures should be considered. The occurrence of mesial buccal root fractures may be related to root canal treatment. Therefore, the risk of mesial buccal root fractures caused by iatrogenic factors should be minimized.

[An anatomical study of maxillary sinus septum of Han population in Jiangsu region using cone-beam CT].

PURPOSE: To examine the anatomical variation of maxillary sinus septum of Han nationality in Jiangsu region by using cone-beam computed tomography (CBCT) combined with Simplant software in order to provide anatomical basis and operation instruction for oral implants after maxillary sinus lifting. METHODS: CBCT image data were collected from 424 patients for analysis of maxillary sinus septa. Digital imaging and communications in medicine (Dicom) image files were fed into the computer-aided Simplant software and used to analyze the prevalence, location, height, orientation, and morphology of maxillary sinus septa through three-dimensional reconstruction. The data was analyzed with SPSS17.0 software package. RESULTS: The proportion of the occurrence of maxillary sinus septa in 424 subjects was 44.81% and 21.23% of the subjects (n=90) had multiple sinus septa, while 20.52% had bilateral sinus septa (n=87). Totally 848 maxillary sinuses were observed in this study and 277 sinuses had septa with a proportion of 32.67%. The prevalence of septa was not significantly related to gender, age, and the presence or absence of teeth. Septa were located most frequently in the middle of maxillary sinus (59.94%). The mean height of sinus septa was (5.90±3.65) mm and (5.54±2.87) mm in the right and left maxillary sinus, respectively. The mean length of sinus septa was (8.15±2.40) mm and (7.88±2.73) mm in the right and left maxillary sinus, respectively. CONCLUSIONS: Nearly 44.81% of Han population in Jiangsu region have maxillary sinus septa. The CBCT imaging technique can provide comprehensive and accurate quantitative analysis of maxillary sinus septa and is meaningful to provide anatomical basis and clinical guidance before sinus augmentation procedures.