RESUMO
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
RESUMO
The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe conditions. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected whole-body metabolism of the patients. In particular, malic acid of the TCA cycle and carbamoyl phosphate of urea cycle reveal the altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in fatal patients compared with mild patients. And more importantly, guanosine monophosphate (GMP), which is mediated by not only GMP synthase but also CD39 and CD73, is significant changed between healthy subjects and COVID-19 patients, as well as between the mild and fatal groups. In addition, the dyslipidaemia was observed in COVID-19 patients. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID- 19 and potential therapeutic targets, as well as important resource for further studies of COVID-19 pathogenesis.
RESUMO
<p><b>OBJECTIVE</b>To recognize changes in the contents of ingredients of Andrographis Tablet in the process of production.</p><p><b>METHOD</b>Adopting TLCS, TLC, HPLC to detect effective contents of ingredients which are produced in every stage of process of Andrographis Table's production.</p><p><b>RESULT</b>Handling with the fresh Herba Andrographis according to current pharmacopeoia's technology, it showed that only dehyandrographolide can be detected. It indicated that the main factor that leads to chemical change is the heating process in the process of production.</p><p><b>CONCLUSION</b>Avoiding heating treatment or reducing heating treatment time is the main factor to protect the effective ingredients.</p>
