基于NGS的染色质测序在肿瘤研究中的应用

染色质是真核生物细胞核内由核酸和蛋白质组成的复合结构,有着精密且复杂的三维结构。染色质除基本的DNA序列外,内部还存在着不同化学修饰,DNA-蛋白质相互作用,DNA-DNA相互作用和DNA-RNA相互作用,以上这些若发生改变都可能在肿瘤发生发展过程中起到至关重要的作用。通过不同的染色质测序方法,可以解析出这些改变,并进一步加深研究者对肿瘤形成机制的理解,最终应用于肿瘤的治疗。本文对常见的染色质测序技术部分原理和应用进行综述。     

Development of a fluorescent probe hydrolysis-insulated isothermal PCR for rapid and sensitive on-site detection of African swine fever virus

Highlights
1. A probe-based insulated isothermal PCR (iiPCR) assay was developed for rapid and onsite detection of ASFV.
2. The developed iiPCR showed similar sensitivity and specificity with OIE recommended real-time PCR.
3. Blood samples could be directly applied as PCR template in iiPCR without DNA extraction.     

Endothelial S1pr1 regulates pressure overload‐induced cardiac remodelling through AKT‐eNOS pathway

Cardiac vascular microenvironment is crucial for cardiac remodelling during the process of heart failure. Sphingosine 1‐phosphate (S1P) tightly regulates vascular homeostasis via its receptor, S1pr1. We therefore hypothesize that endothelial S1pr1 might be involved in pathological cardiac remodelling. In this study, heart failure was induced by transverse aortic constriction (TAC) operation. S1pr1 expression is significantly increased in microvascular endothelial cells (ECs) of post‐TAC hearts. Endothelial‐specific deletion of S1pr1 significantly aggravated cardiac dysfunction and deteriorated cardiac hypertrophy and fibrosis in myocardium. In vitro experiments demonstrated that S1P/S1pr1 praxis activated AKT/eNOS signalling pathway, leading to more production of nitric oxide (NO), which is an essential cardiac protective factor. Inhibition of AKT/eNOS pathway reversed the inhibitory effect of EC‐S1pr1‐overexpression on angiotensin II (AngII)‐induced cardiomyocyte (CM) hypertrophy, as well as on TGF‐β‐mediated cardiac fibroblast proliferation and transformation towards myofibroblasts. Finally, pharmacological activation of S1pr1 ameliorated TAC‐induced cardiac hypertrophy and fibrosis, leading to an improvement in cardiac function. Together, our results suggest that EC‐S1pr1 might prevent the development of pressure overload‐induced heart failure via AKT/eNOS pathway, and thus pharmacological activation of S1pr1 or EC‐targeting S1pr1‐AKT‐eNOS pathway could provide a future novel therapy to improve cardiac function during heart failure development.     

Topoisomerase I‐Mediated Antiproliferative Activity of 10‐Substituted and 12‐Substituted Homocamptothecins

Homocamptothecin (hCPT) is an E‐ring modified camptothecin (CPT) analogue, which showed pronounced inhibitory activity of topoisomerase I. In search of novel hCPT‐type anticancer agents, two series of hCPT derivatives were synthesized and evaluated in vitro against three human tumor cell lines. The results indicated that the 10‐substituted hCPT derivatives had a considerably higher cytotoxic activity than the 12‐substituted ones. Among the 10‐substituted compounds, 8a, 8b, 9b , and 9i showed an equivalent or even more potent activity than the positive control drug topotecan against the lung cancer cell line A‐549. Moreover, the hCPT analogues 8a and 8b exhibited a higher topoisomerase I inhibitory activity than CPT at a concentration of 100 μM .     

Aluminum Tolerance in Moso Bamboo (<Emphasis Type="Italic">Phyllostachys pubescens</Emphasis>)

Moso bamboo (Phyllostachys pubescens) is widely distributed in the acid soil region of Southern China, where great potential of aluminum (Al) toxicity exists. To evaluate the Al tolerance of Moso bamboo, seed germination and root elongation were compared with two rice cultivars, and physical and physiological damages were examined under various levels of Al stress. Results showed that Moso bamboo seed germination was inhibited when Al concentration increased to 500 μM, and the median lethal concentration was 2,000 μM. Comparatively, the rice seed germination was not inhibited even at a concentration of 2,000 μM Al. Aluminum accumulated mainly in the cell wall of root apices, and entered into protoplasts as treating time prolonged and/or Al concentration increased, which resulted in apoptosis. The bamboo root epidermis degraded significantly in the presence of 2,000 μM Al. In conclusion, Moso bamboo is moderately weak in Al tolerance.     

Synthesis of novel steroidal agonists,partial agonists,and antagonists for the glucocorticoid receptor

Adverse effects of glucocorticoids could be limited by developing new compounds that selectively modulate anti-inflammatory activity of the glucocorticoid receptor (GR). We have synthesized a novel series of steroidal GR ligands, including potent agonists, partial agonists and antagonists with a wide range of effects on inhibiting secretion of interleukin-6. Some of these new ligands were designed to directly impact conformational stability of helix-12, in the GR ligand-binding domain (LBD). These compounds modulated GR activity and glucocorticoid-induced gene expression in a manner that was inversely correlated to the degree of inflammatory response. In contrast, compounds designed to directly modulate LBD epitopes outside helix-12, led to dissociated levels of GR-mediated gene expression and inflammatory response. Therefore, these new series of compounds and their derivatives will be useful to dissect the ligand-dependent features of GR signaling specificity.