Mechanism and Application of α7 nAChR in Cholinergic Antiinflammatory Pathway / 中国生物化学与分子生物学报

Cholinergic anti-inflammatory pathway in which acetylcholine released as the neurotransmitter, plays an important role in nerve-immune regulation. In this pathway, with the vagus nerve in the central nervous system as a starting point, the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) on the surface of immune cell membrane is the key functional part. The interaction between electrical and chemical signals regulates the inflammation in the body via modulation of the JAK-STAT3, PI3K-Akt and other signaling pathways and the nuclear translocation of NF-κB, leading to inhibition of the release of pro-inflammatory factors and promotion of the release of anti-inflammatory factors. However, the detailed mechanism is far from clear. Studies have shown that the cholinergic anti-inflammatory pathway can be activated by drug targeting α7 nAChR and electrical stimulation of vagus nerve. Activation of α7 nAChR has the advantages of simple operation, less damage and significant effect. The commonly used drugs are selective agonists such as PNU282987 and GTS-21, and non-selective agonists such as nicotine. And this method has been found to play a role in the treatment of peripheral organ inflammatory diseases such as sepsis, ischemia-reperfusion injury, gastroenteritis, osteoarthritis and autoimmune diseases. As a key factor in the cholinergic anti-inflammatory pathways, α7 nAChR has become a potential therapeutic target for many inflammatory diseases. This paper reviewed the anti-inflammatory mechanism and activation mode of α7 nAChR involved in cholinergic anti-inflammatory pathway, as well as its application in inflammatory diseases in recent years, which may provide a reference for future research on its detailed mechanism of action and potential application as a new therapeutic target.

Research progress of famesyltransferase and its inhibitors in cancer therapy / 中国药理学通报

Famesyltransferase, a membrane-associated protein, catalyzes the addition of the 15-carbon fragment of famesyl diphosphate to the cysteine SH group of the CAAX motif containing protein substrates to regulate the function of target proteins through famesylation. As one of the most important target proteins of FTase, oncogenic forms of Ras mutants have been reportedly involved in more than 30% human cancers, and are known to play critical roles in cancer development and progression. Despite decades of research, Ras inhibitors are so elusive that no therapeutic agents directly targeting Ras mutants have been clinically approved, the primary reason for which is the lack of druggable pockets on the surface of Ras. Therefore, FTase, the main regulator of Ras protein, has gradually become a research hotspot, and many FTase inhibitors have been developed, synthesized and used for the treatment of malignant tumors. In the present review, we briefly describe the regulation of Ras functions by FTase and the role of FTase in cancers, and mainly explore the research progress of FTase inhibitors as a promising strategy for cancer therapy.

Prokaryotic expression and purification of recombinant CARD9-MBP fusion protein / 医学研究生学报

Objective　CARD9 can activate several pathways involved in immunity, such as NF-ΚB, MAPK, etc. However the mechanism of this process has not yet been elucidated. For conducting relevant experiments in vitro, a prokaryotic expression vector of CARD9-MBP fusion protein has to been construct, and the fusion protein need to be expressed and purified.　Methods　The coding sequence of CARD9 and MBP genes were amplified by PCR and the recombinant plasmid was correctly inserted into the pET-30a(+) vector. The recombinant plasmid was transformed into E.coli DH5α competent cells and proceeded PCR identification, restriction analysis and gene sequencing. The correct recombinant plasmid was transformed into E.coli BL21(DE3) competent cells. The target protein was induced to express by IPTG under different conditions. Relative molecular weight of the target protein was detected by SDS-PAGE electrophoresis. The CARD9-MBP fusion protein was purified by MBP maltose chromatography column and gel filtration chromatography column, and identificated by MALDI-TOF mass spectrometry after MBP-tag to be removed by HRV3C enzyme.　Results　The CARD9-MBP fusion protein was successfully constructed and confirmed by PCR and restriction analysis. The result of gene sequencing was consistent with the target sequence. The SDS-PAGE electrophoresis showed that the target protein with molecular mass (MR) about 105 000 was successfully induced to express in E.coli BL21 (DE3). A quite pure CARD9-MBP fusion protein was obtained by purification of MBP maltose chromatography column. Identification by MALDI-TOF mass spectrometry demonstrated that the target protein after MBP-tag to be removed by HRV3C enzyme is CARD9 protein. In the later stage, gel filtration chromatography column was used to obtain further pure CARD9-MBP fusion protein.　Conclusion　The prokaryotic expression vector of CARD9-MBP fusion protein was successfully constructed and a large number of soluble protein expressed. The purified target protein can be obtained by purification with MBP maltose chromatography column and gel filtration chromatography column.

Current sharing status of medical data in Hunan Province and its restrictive factors and countermeasures / 中华医学图书情报杂志

The current sharing of medical data and its restrictive factors were surveyed by literature and question-naire investigation and analyzed with statistical analysis tools such as SPSS and Excel, which showed the influence of different restrictive factors on different populations. Certain measures were put forward for speeding up the sha-ring of scientific data, improving the medical treatment and academic level, strengthening the competitive power of hospitals and higher education institutions in Hunan Province.