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Acta Pharmaceutica Sinica B ; (6): 308-315, 2022.
Article in English | WPRIM | ID: wpr-929295


Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an 18F-labeled MAGL inhibitor ([18F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [18F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [18F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [18F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [18F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [18F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

China Medical Equipment ; (12): 113-115,116, 2013.
Article in Chinese | WPRIM | ID: wpr-598577


Objective: To investigate the value of enhanced 3D SPACE sequence in displaying brachial plexus. Methods:35 healthy volunteers with no history of brachial plexus injury of brachial plexus MRI examinations by DWIBS scan, and SPACE scanned. Analysis and comparison of DWIBS sequences, sequences of SPACE provides a clear display of the brachial plexus, and two sets of image sequence average signal-to-noise ratio (SNR) and the contrast to noise ratio (CNR). Results:A total of 35 cases 70 lateral brachial plexus after coronary DWIBS is clearly displayed on the sequence;the partial medial cord of brachial plexus, beams and lateral beams can also be displayed in the SPACE sequence. SPACE sequence of image signal-to-noise ratio and contrast noise ratio than the DWIBS sequence, and the difference is statistically significant. Conclusion:SPACE sequence can clearly show the brachial plexus, and DWIBS sequences compared to the normal image has a higher resolution of the brachial plexus.

Article in Chinese | WPRIM | ID: wpr-516665


Objective To study the expression of CD44V6 in human epidermal tumours and malignant melanoma. Methods The expression of CD44V6 was detected by an immunohistochemical technique in squamous cell carcinoma(SCC), basal cell carcinoma(BCC) and malignant melanoma(MM). Results CD44V6 was expressed on the membrane of tumour cells of 10 patients with SCC, and there was downregulation of CD44V6 expression which along with the decrease of differentiation of SCC tumour cells. Tumour cells of 8 patients with MM and 10 patients with BCC did not express CD44V6. Conclusion Our findings suggest that CD44V6 expression is correlated with the types of skin tumours.