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Objective: To design and synthesize APC/Asef peptide inhibitors and investigate the structure-activity relationship between peptides inhibitors and APC protein for exploring better inhibitors. Methods: Based on the best-class inhibitor we had found before-MAI-400, eleven peptide inhibitors were designed, which included the changes of N-terminal capping group, the first amino acid Ala, the fifth amino acid Leu and the last amino acid Glu. According to the results of fluorescence polarization activity detection system and molecular docking, the structure-activity relationship of peptide inhibitors was investigated. Results: Among the eleven peptides, MPI-11 had the highest affinity, whose half maximal inhibitory concentration (IC50) was 0.973 1 mmol/L. The capping group of peptide N-terminal with tert-butoxycarbonyl group reduced the activity slightly. The substitution of the Ala caused different results, changing into Trp, His and Thr definitely reduced the activity but the substitution by Tyr or Phe did not influence the activity too much. And introducing benzene ring into the side chain of Leu had few effects on activity improving. The substitution of side chain carboxyl for amide at the C-terminal glutamate had little effect on the activity. Conclusion: Among the eleven peptides, the capping group of peptide N-terminal cannot be substituted into small groups and Ala cannot be substituted into other amino acids.
ABSTRACT
Autism spectrum disorder(ASD) is a group of multi-factor brain development disorders. At present,ASD treatment is still based on behavioral intervention,for there are no specific drugs. ASD comorbidities are extremely common in children with ASD,and the presence of comorbidities has an important impact on the treatment and prognosis of ASD. In recent years,the etiology and behavioral intervention of ASD has become a research hotspot at home and abroad,but there are few studies on comorbidity and drug intervention. Therefore,we summarize relevant literatures at home and abroad, hoping to be helpful for clinical research on ASD comorbidity and drug treatment.
ABSTRACT
<p><b>INTRODUCTION</b>Endometrial carcinoma is the most common gynaecological malignancy. Studies have shown that laparoscopic total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection was advantageous compared to laparotomy in reducing length of stay and intraoperative blood loss. However, these studies had a predominantly Caucasian population. A comparison study was conducted among the Singapore population to investigate the differences in oncological and surgical outcomes between these two methods.</p><p><b>METHODS</b>A retrospective, single-centre cohort study was conducted. Records of hospitalised patients with Stage 1 endometrioid carcinoma from 2008 to 2014 were extracted for review. Demographic data and study-specific parameters, including operative time, length of hospitalisation, intraoperative and postoperative complications, pain scores, final staging and recurrence rates, were compared between the two groups.</p><p><b>RESULTS</b>475 endometrioid carcinoma patients were admitted for surgical staging, among whom 374 fulfilled our inclusion criteria. Out of these patients, 229 underwent laparotomy and 145 underwent laparoscopy. The race, parity and body mass index of both groups were comparable. Patients who underwent laparoscopic surgery reported reduced pain score within two hours postoperatively (p = 0.007) and at Postoperative Days 1, 2 and 3 (p < 0.001). Laparoscopic surgery also illustrated better outcomes such as reduced length of stay (p < 0.001) and reduced intraoperative blood loss (p < 0.001). The operative time, recurrence rate and disease-free intervals were comparable between both groups.</p><p><b>CONCLUSION</b>Laparoscopy offered similar oncological outcomes with superior surgical outcomes compared to laparotomy. It provides a suitable alternative in the surgical staging of endometrioid carcinoma.</p>