Synthesis, biological activity and mechanism of action of novel allosecurinine derivatives as potential antitumor agents.

Cancer with low survival rates is the second main cause of death among all diseases in the world and consequently, effective antineoplastic agents are urgently needed. Allosecurinine is a plant-derived indolicidine securinega alkaloid shown bioactivity. The object of this study is to investigate synthetic allosecurinine derivatives with considerable anticancer capacity against nine human cancer cell lines as well as mechanism of action. We synthesized twenty-three novel allosecurinine derivatives and evaluated their antitumor activity against nine cancer cell lines for 72 h by MTT and CCK8 assays. FCM was applied to analyze the apoptosis, mitochondrial membrane potential, DNA content, ROS production, CD11b expression. Western blot was selected to analyze the protein expression. Structure-activity relationships were established and potential anticancer lead BA-3 which induced differentiation of leukemia cells towards granulocytosis at low concentration and apoptosis at high concentration was identified. Mechanism studies showed that mitochondrial pathway mediated apoptosis within cancer cells with cell cycle blocking was induced by BA-3. In addition, western blot assays revealed that BA-3 induced expression of the proapoptotic factor Bax, p21 and reduced the levels of antiapoptotic protein such as Bcl-2, XIAP, YAP1, PARP, STAT3, p-STAT3, and c-Myc. Collectively, BA-3 was a lead compound for oncotherapy at least in part, through the STAT3 pathway. These results were an important step in further studies on allosecurinine-based antitumor agent development.

Manual compass measurement and trigonometric determination of proptosis.

PURPOSE: To determine the accuracy of manual compass measurement and trigonometric determination of proptosis (MCMATDP). METHODS: This agreement study included 120 eyes without eye diseases or injury of 60 patients who visited the ophthalmic clinic of Peking University Shenzhen Hospital from February 2020 to June 2020. The absolute values of proptosis were measured by MCMATDP and computed tomography (CT). The differences between the two methods were shown by Bland-Altman plot. RESULTS: The cohort comprised 25 males and 35 females (average age 38.3 years). The absolute value of proptosis measured by CT was correlated with the MCMATDP. Further analysis showed that a 95% limit of agreement (LoA) was - 0.53 to 0.60 mm in the right eye and - 0.46 to 0.55 mm in the left eye between CT and MCMATDP. In addition, the 95% LoA was - 0.49 to 0.60 mm in both eyes between the two methods. All points were < 5% in Bland-Altman plots. CONCLUSIONS: Compared to CT, MCMATDP is rather consistent in proptosis measurement. The new method is feasible in clinical practice when measuring proptosis. With the development of non-contact intelligent measurement software and the continuous improvement in measurement accuracy, a non-invasive, simple, and inexpensive measurement mode is true based on the theory of MCMATDP.

Pharmacological activity and mechanism of pyrazines.

Heterocycles are common in the structure of drugs used clinically to deal with diseases. Such drugs usually contain nitrogen, oxygen and sulfur, which possess electron-accepting capacity and can form hydrogen bonds. These properties often bring enhanced target binding ability to these compounds when compared to alkanes. Pyrazine is a nitrogen-containing six-membered heterocyclic ring and many of its derivatives are identified as bioactive molecules. We review here the most active pyrazine compounds in terms of their structure, activity in vitro and in vivo (mainly antitumor activity) and the reported mechanisms of action. References have been downloaded through Web of Science, PubMed, Science Direct, Google Scholar and SciFinder Scholar. Publications reporting only the chemistry of pyrazine derivatives are beyond the scope of this review and have not been included. We found that compounds in which a pyrazine ring was fused into other heterocycles especially pyrrole or imidazole were the highly studied pyrazine derivatives, whose antineoplastic activity had been widely investigated. To the best of our knowledge, this is the first review of pyrazine derivatives and their bioactivity, especially their antitumor activity. This review should be useful for those engaged in development of medications based on heterocyclic compounds especially those based on pyrazine.

The feasibility analysis of calculating proptosis by simple Pythagorean theorem.

PURPOSE: We propose a new method to analyze the feasibility of calculating proptosis on the basis of simple Pythagorean theorem. METHOD: This is a non-inferiority trial, and the registration number is ChiCTR1900026490. The absolute value of proptosis of two eyes of patients without eye injury or diseases visiting our clinic from December 2017 to June 2019 was measured by computed tomography, Hertel exophthalmometer, and by simple Pythagorean theorem. With the application of MedCalc software version 19.0.4, the differences between these methods in two eyes were showed by Bland and Altman plot. RESULTS: A 95% limit of agreement between computed tomography and Hertel exophthalmometer is -0.7 to 0.62 mm in right eye proptosis. A total of 4.44% (4/90) points were outside 95% limit of agreement. Similarly, the same method was used to compare the proptosis between computed tomography and other ways. We also compared the proptosis measured by homolateral and heterolateral simple Pythagorean theorem method in order to find out the consistence between them. The points in all Bland and Altman plots were lower than 5%, which means that the results of comparison between any two methods had a good consistency in the measurement of proptosis of both eyes. CONCLUSION: Pythagorean theorem can be applied to evaluate proptosis and has a good consistency comparing with computed tomography and the Hertel exophthalmometer. The method can be used for measuring proptosis of unilateral orbital, maxillofacial trauma, and dysplasia accurately. It is practical in clinical use of proptosis assessment because of its accuracy, reliability, and simplicity.