ABSTRACT
Objective To investigate the role of TRIM65 on DSS induced colitis and the underlying molecular mechanisms. Methods Trim65+/+ and Trim65-/- mice were administered with 3% (w/v) DSS in their drinking water for 5 consecutive days and then were switched to sterile water for 2 days. DSS treated mice were monitored daily for the clinical symptoms (bodyweight, stool consistency and rectal bleeding score). Mice were sacrificed on day 7 to measure colon length. Colon homogenates were collected to measure MPO activity and detect cleaved caspase-1 and mature IL-1β by Enzyme linked immunosorbent assay (ELISA) and Western blot. Trim65-/- mice were intraperitoneally injected with NLRP3 inflammasome inhibitor MCC950, and were given the above treatment to determine the effect of MCC950 on colitis in Trim65-/- mice. Results The results showed that deletion of Trim65 significantly enhanced weight loss and colon shortening in DSS mice, increased disease activity index and histopathological score, induced the activity of MPO, and promoted the F4/80+ immune cell infiltration, the activation of caspase-1 and the secretion of mature IL-1 in the colon of DSS mice. The NLRP3 inflammasome inhibitor MCC950 alleviated DSS induced colitis symptoms and inflammation levels in trim65 deficient mice. Conclusion TRIM65 plays an anti-inflammatory role in DSS induced colitis mice by inhibiting the activation of NLRP3 inflammasome.
ABSTRACT
Liver fibrosis is a symbolic process of many chronic liver diseases, and liver biopsy is the gold standard for the diagnosis of liver fibrosis in clinical practice. At present, there is a lack of effective methods for the noninvasive diagnosis of early-stage liver fibrosis. The process of liver fibrosis is accompanied by complicated changes at the molecular level, which are associated with the progression of liver fibrosis. As an imaging examination which can provide the information at the molecular level such as tissue function and metabolism, positron emission tomography (PET) has the ability to monitor such quantitative information. This article mainly introduces the principles of specific molecular probes for PET used in the diagnosis of early-stage liver fibrosis, summarizes the value of these specific molecular probes in the diagnosis and staging of early-stage liver fibrosis, and points out that it is necessary to find more specific molecular probes for the diagnosis of early-stage liver fibrosis.