Aristolochic acids (AAs) and their derivatives exist in multiple Aristolochiaceae species which had been or are being used as medicinal materials. During the past decades, AAs have received increasing attention due to their nephrotoxicity and carcinogenecity. Elimination of AAs in medicinal materials using biotechnological approaches is important to improve medication safety. However, it has not been achieved because of the limited information of AA biosynthesis available. Here, we report a high-quality reference-grade genome assembly of the AA-containing vine, Aristolochia contorta. Total size of the assembly is 209.27 Mb, which is assembled into 7 pseudochromosomes. Synteny analysis, Ks distribution and 4DTv suggest absences of whole-genome duplication events in A. contorta after the angiosperm-wide WGD. Based on genomic, transcriptomic and metabolic data, pathways and candidate genes of benzylisoquinoline alkaloid (BIA) and AA biosynthesis in A. contorta were proposed. Five O-methyltransferase genes, including AcOMT1–3, AcOMT5 and AcOMT7, were cloned and functionally characterized. The results provide a high-quality reference genome for AA-containing species of Aristolochiaceae. It lays a solid foundation for further elucidation of AA biosynthesis and regulation and molecular breeding of Aristolochiaceae medicinal materials.
Background: Plants produce thousands of chemically diverse secondary metabolites, many of which have valuable pharmaceutical properties. There is much interest in the synthesis of these pharmaceutically-valuable compounds, including the key enzymes and the transcription factors involved. The function and regulatory mechanism of transcription factors in biotic and abiotic stresses have been studied in depth. However, their regulatory roles in the biosynthesis of bioactive compounds, especially in medicinal plants, have only begun. Objective: Here we review what is currently known about how transcription factors contribute to the synthesis of bioactive compounds (alkaloids, terpenoids, flavonoids, and phenolic acids) in medicinal plants. Results and Conclusion: Recent progress has been made in the cloning and characterization of transcription factors in medicinal plants on the genome scale. So far, several large transcription factors have been identified in MYB, WRKY, bHLH, ZIP, AP2/ERF transcription factors. These transcription factors have been predicted to regulate bioactive compound production. These transcription factors positively or negatively regulate the expression of multiple genes encoding key enzymes, and thereby control the metabolic flow through the biosynthetic pathway. Although the research addressing this niche topic is in its infancy, significant progress has been made, and advances in high-throughput sequencing technology are expected to accelerate the discovery of key regulatory transcription factors in medicinal plants. This review is likely to be useful for those interested in the synthesis of pharmaceutically-valuable plant compounds, especially those aiming to breed or engineer plants that produce greater yields of these compounds.
PurposeCapsid protein L2 is the minor capsid protein of human papillomavirus 16 (HPV16). Although L2-based vaccines were developed, the therapeutic effect of recombinant viral capsid protein L2 (rVL2) was still to be illustrated.MethodsWe used glucose uptake and lactate production assay to verify the inhibitory effect of rVL2 on the glucose metabolism in cervical cancer cells. Secondly, we performed gene-chip assay, RT-PCR, and Western blot to determine the role of ITGB7/C/EBPβ signaling pathway in rVL2-mediated glucose metabolism in vitro. Finally, we used an animal model to verify the function of rVL2 in cervical cancer.ResultsWe found that rVL2 reduced glucose uptake and lactate production levels in cervical cancer cells, which caused the inhibition of cell proliferation. rVL2 decreased the expression levels of key metabolic enzymes, including GLUT1, LDHA, and ALDOA, to affect cell metabolism in cervical cancer cells by inhibiting ITGB7/C/EBPβ signaling pathway in vitro and in vivo.ConclusionThese results demonstrated the vital role of rVL2 in the glycolysis-induced cell growth and proliferation via suppressing ITGB7/C/EBPβ signaling axis.
The present study aimed to evaluate the cardioprotective effects of a Rho-kinase inhibitor, Y-27632, and the underlying mechanisms. A rat model of myocardial ischemia-reperfusion (I/R) injury was generated by ligation of the coronary artery, and global ischemia of isolated rat hearts was conducted using the Langendorff system. Staining with triphenyltetrazolium chloride (TTc) and hematoxylin and eosin was performed to analyze the myocardial infarct size and histopathological alterations of the I/R-induced rat heart. In addition, coronary flow, myocardial contractility and an electrocardiogram were analyzed. The effects of Y-27632 on inflammatory cytokines and cardiac enzymes in the serum were assessed by ELISA. The expression of apoptosis-and inflammation-associated proteins was also analyzed via western blotting. Rats in the Y-27632 group exhibited alleviated myocardial I/R injury according to TTc staining and histopathological diagnosis. Additionally, Y-27632 restored the ST segment. The data of coronary flow and myocardial contractility in isolated rat hearts indicated that Y-27632 improved heart function following I/R. The levels of inflammatory cytokines and cardiac enzymes in the serum were downregulated by Y-27632. The mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways were inhibited by Y-27632. Furthermore, apoptosis-associated protein expression in rats and the isolated hearts was effectively inhibited by Y-27632. In conclusion, the findings of the present study indicated that Y-27632 attenuated myocardial injury via inhibiting the activation of the MAPK and NF-κB signaling pathways; thus, apoptosis and the inflammatory response were suppressed.
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