We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of 'hit' compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21 h, 21 k, 21 n, 21 t, and 21 x with improved activities (IC50 =12-30 μM) and low Jurkat cytotoxicities (IC50 >100 μM). These new compounds also inhibited the secretion of IFN-γ and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity.
OBJECTIVES
A thymic epithelial tumour is the most common primary tumour in the anterior mediastinum of adults. A few retrospective studies compared the short-term outcomes between robotic-assisted thymectomy (RAT) and video-assisted thymectomy (VAT). So, it is necessary to conduct a meta-analysis to further compare these 2 surgical techniques.
METHODS
EMBASE, Medline and Web of Science were used. Thesaurus terms and medical subject headings were used in Medline and EMBASE, respectively. The Newcastle-Ottawa scale was used for grading because the included studies were all case-control studies.
RESULTS
Nine studies were included in the meta-analysis with a total of 723 patients, including 315 patients in the RAT group and 408 patients in the VAT group. The meta-analysis [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.06–0.94; P = 0.041], indicating that RAT yielded a significantly lower rate of conversion compared with VAT. Duration of drainage with RAT was significantly less than that with VAT (weighted mean difference = −1.10; 95% CI −1.98 to −0.22; P = 0.014). The pooled analysis (weighted mean difference = −103.6; 95% CI −199.21 to −7.98; P = 0.034) suggested that patients in the RAT group had less drainage than those in the VAT group. The recurrence rates in both groups were comparable (OR 0.19, 95% CI 0.03–1.20; P = 0.078).
CONCLUSIONS
RAT has advantages over VAT in terms of short-term outcomes such as shorter duration of drainage, less total drainage and a lower rate of conversion. The recurrence rate was comparable between the 2 techniques. Therefore, RAT could be considered as an alternative treatment for diseases of the thymus.
BACKGROUNDInvaginated teeth pose greater challenges in clinical management because of their complex configuration. With advancements in equipment and materials, such as the dental operation microscope, cone-beam computed tomography and mineral trioxide aggregate, the preservation rate of type III dens invaginatus could be greatly increased.
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