Dentonnash6371

Post-aortic left brachiocephalic vein (PALBV) is one of the rare congenital vessel abnormalities associated with congenital heart disease. As only a few reports of surgical treatment for thymic tumor in patients with PALBV are available, this study reports the case of a patient with PALBV who underwent surgical treatment for thymoma. In a 60-year old woman, a nodule in the anterior mediastinum was detected on chest computed tomography (CT) during examination for arrhythmia. Thymoma was suspected, and surgical resection was considered. PALBV was detected on a contrast CT scan before surgery. Video-assisted thoracoscopic surgery was used to perform thymectomy using the subxiphoid dual-port approach. This method provided an appropriate view of the operative field and made it easy to confirm the presence of PALBV and identify the thymic veins branching off from the internal thoracic vein.Legumain is a newly discovered lysosomal cysteine protease that can cleave asparagine bonds and plays crucial roles in regulating immunity and cancer metastasis. HRS-4642 mouse Legumain has been shown to be highly expressed in various solid tumors, within the tumor microenvironment and its levels are directly related to tumor metastasis and poor prognosis. Therefore, legumain presents as a potential cancer therapeutic drug target. In this study, we have identified esomeprazole and omeprazole as novel legumain small molecule inhibitors by screening an FDA approved-drug library. These compounds inhibited enzyme activity of both recombinant and endogenous legumain proteins with esomeprazole displaying the highest inhibitory effect. Further molecular docking analysis also indicated that esomeprazole, the S- form of omeprazole had the most stable binding to legumain protein compared to R-omeprazole. Transwell assay data showed that esomeprazole and omeprazole reduced MDA-MB-231 breast cancer cell invasion without effecting cell viability. Moreover, an in vivo orthotopic transplantation nude mouse model study showed that esomeprazole reduced lung metastasis of MDA-MB-231 breast cancer cells. These results indicated that esomeprazole has the exciting potential to be used in anti-cancer therapy by preventing cancer metastasis via the inhibition of legumain enzyme activity. Graphical abstract.Multiple myeloma (MM) is a devastating disease with low survival rates worldwide. The mean lifetime of patients may be extendable with new drug alternatives. Aurora A kinase (AURKA) is crucial in oncogenesis, because its overexpression or amplification may incline the development of various types of cancer, including MM. Therefore, inhibitors of AURKA are innovative and promising targets. Natural compounds always represented a valuable resource for anticancer drug development. In the present study, based on virtual drug screening of more than 48,000 natural compounds, the antibiotic deschloro-chlorotricin (DCCT) has been identified to bind to AURKA with even higher binding affinity (free bindung energy -12.25 kcal/mol) than the known AURKA inhibitor, alisertib (free binding energy -11.25 kcal/mol). The in silico studies have been verified in vitro by using microscale thermophoresis. DCCT inhibited MM cell lines (KMS-11, L-363, RPMI-8226, MOLP-8, OPM-2, NCI-H929) with IC50 values in a range from 0.01 to 0.12 μM. Furthermore, DCCT downregulated AURKA protein expression, induced G2/M cell cycle arrest and disturbed the cellular microtubule network as determined by Western blotting, flow cytometry, and fluorescence microscopy. Thus, DCCT may be a promising lead structure for further derivatization and the development of specific AURKA inhibitors in MM therapy.C-reactive protein (CRP) has been studied extensively for association with a large number of non-infectious diseases and outcomes. We aimed to evaluate the breadth and validity of associations between CRP and non-infectious, chronic health outcomes and biomarkers. We conducted an umbrella review of systematic reviews and meta-analyses and a systematic review of Mendelian randomization (MR) studies. PubMed, Scopus, and Cochrane Database of Systematic Reviews were systematically searched from inception up to March 2019. Meta-analyses of observational studies and MR studies examining associations between CRP and health outcomes were identified, excluding studies on the diagnostic value of CRP for infections. We found 113 meta-analytic comparisons of observational studies and 196 MR analyses, covering a wide range of outcomes. The overwhelming majority of the meta-analyses of observational studies reported a nominally statistically significant result (95/113, 84.1%); however, the majority of the meta-analyses displayed substantial heterogeneity (47.8%), small study effects (39.8%) or excess significance (41.6%). Only two outcomes, cardiovascular mortality and venous thromboembolism, showed convincing evidence of association with CRP levels. When examining the MR literature, we found MR studies for 53/113 outcomes examined in the observational study meta-analyses but substantial support for a causal association with CRP was not observed for any phenotype. Despite the striking amount of research on CRP, convincing evidence for associations and causal effects is remarkably limited.In the present study, we investigated whether electroporation could be used for one-step multiplex CRISPR/Cas9-based genome editing, targeting IL2RG and GHR in porcine embryos. First, we evaluated and selected guide RNAs (gRNAs) by analyzing blastocyst formation rates and genome editing efficiency. This was performed in embryos electroporated with one of three different gRNAs targeting IL2RG or one of two gRNAs targeting GHR. No significant differences in embryo development rates were found between control embryos and those subjected to electroporation, irrespective of the target gene. Two gRNAs targeting IL2RG (nos. 2 and 3) contributed to an increased biallelic mutation rate in porcine blastocysts compared with gRNA no. 1. There were no significant differences in the mutation rates between the two gRNAs targeting GHR. In our next experiment, the mutation efficiency and the development of embryos simultaneously electroporated with gRNAs targeting IL2RG and GHR were investigated. Similar embryo development rates were observed between embryos electroporated with two gRNAs and control embryos.