Identification of Diagnostic Magnetic Resonance Imaging Findings in 47 Shoulders with Subcoracoid Impingement Syndrome by Comparison with 100 Normal Shoulders.

BACKGROUND The aim of this study was to identify the diagnostic magnetic resonance imaging (MRI) findings in 47 shoulders with subcoracoid impingement syndrome by comparison with 100 normal shoulders. MATERIAL AND METHODS The subcoracoid impingement syndrome group consisted of 47 shoulders with subcoracoid impingement syndrome and the normal group consisted of 100 normal shoulders. The MRI parameters - coracoids-humeral distance (CHD), coracoid index (CI), height of the lesser tuberosity (HLT), coracoid obliquity (CO), coracoglenoid angle (CGA), coracohumeral angle (CHA), width of the subscapular tendon (WST), and contact distance between subscapular tendon and coracoid process (CD) - were compared between the subcoracoid impingement syndrome group and the normal group. The areas under the curves (AUCs) from the receiver operating characteristic (ROC) for single MRI parameters were recorded, in which the MRI parameters with AUC exceeding 0.70 were included in the analysis of combined parameters. Comparisons of ROC were made among single parameters and combined parameters. RESULTS For diagnosing subcoracoid impingement syndrome by using single MRI parameters (CHD, CI, HLT, CGA, CHA, WST, and CD), the AUCs were 0.963, 0.806, 0.745, 0.691, 0.613, 0.685, and 0.614, respectively, of which CHD had the largest AUC. CHD, CI, and HLT (AUC exceeding 0.70) were included in the study of the combined parameters. The AUC of combined CHD and HLT showed a significantly larger AUC than that of CHD (0.986 vs 0.963, P=0.036), and showed no significant difference compared with that of combined CHD, CI, and HLT (0.986 vs 0.987, P=0.882). CONCLUSIONS Measurement of the coracoid-humeral distance and height of the lesser tuberosity were key MRI diagnostic findings for subcoracoid impingement syndrome.

Discovering Peptide Inhibitors of Human Squalene Synthase Through Screening the Phage-Displayed Cyclic Peptide c7c Library.

Many drugs for the treatment of hypercholesterolemia are targeting the enzymes involved in human cholesterol biosynthesis pathway. Squalene synthase, the rate-limiting enzyme located at the downstream of cholesterol synthesis pathway, has become a better candidate to develop next-generation hypocholesterolemia drugs. In the present study, we cloned and expressed the recombinant human squalene synthase (hSQS) as the lure to isolate potential peptide inhibitors from screening the conformation-constrained phage-displayed cyclic peptide c7c library. Their binding capabilities were further estimated by ELISA. Their pharmaceutical potentials were then analyzed through molecular modeling and the ADMET property evaluations. Four ennea-peptides and nine tetra-peptides were finally synthesized to evaluate their inhibitory potentials toward hSQS. The results indicate that the ennea-peptide CLSPHSMFC, tetra-peptides SMFC, CKTE, and WHQW can effectively inhibit hSQS activities (IC50 values equal to 64, 76, 87, and 90 µM, respectively). These peptides may have potentials to develop future cholesterol-lowering therapeutics. The ligand-protein interaction analysis also reveals that the inner hydrophobic pocket could be a more critical site of hSQS.

Exploration of Peptide Inhibitors of Human Squalene Synthase through Molecular Modeling and Phage Display Technique.

Many studies have demonstrated the role of elevated levels of serum cholesterol in the pathogenesis of atherosclerosis and coronary heart disease. Various drugs targeting the key enzymes involved in the cholesterol biosynthesis pathway have been investigated for the treatment of hypercholesterolemia. Human squalene synthase has been one of the most important targets for therapeutic intervention. In the present study, we used the recombinant human squalene synthase as the lure for screening the peptide inhibitors from phage-displayed random peptide library. The tightly bound phages and their derived peptides were further evaluated based on their potential binding capabilities, molecular modeling characteristics and predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. Several hexa-peptides and tetra-peptides were finally synthesized to assay their inhibitory effects toward the recombinant human squalene synthase. The results demonstrated that the hexa-peptide FTACNW and tetra-peptide VACL can inhibit human squalene synthase effectively (with IC50 values near 100 µM) and may have potential to develop further as future hypocholesterolemia agents.