Taurochenodeoxycholic acid mediates cAMP-PKA-CREB signaling pathway / 中国天然药物

Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.

Mechanisms of anti-inflammation of taurochenodeoxycholic acid based on network pharmacology / 药学学报

To investigate the anti-inflammatory mechanisms of taurochenodeoxycholic acid (TCDCA), the molecule structure file of TCDCA was downloaded from PubChem database, PharmMapper and GeneCards were used to predict and screen the targets of TCDCA. STRING database and Cytoscape software were used to construct protein interactions network. GO and KEGG analysis was preformed through STRING database. The key targets were validated by molecular docking and the targets type was attributed by DisGeNET database. The network showed that 89 targets were involved in 68 biological processes including response to stimulus, multicellular organismal process, single-multicellular organism process, response to chemical, response to organic substance, by adjusting 51 signaling pathways, such as pathways in cancer, progesterone-mediated oocyte maturation, MAPK signaling pathway, proteoglycans in cancer. These findings provide an overview of anti-inflammation of TCDCA, which reflects the characteristic of multi-targets and multi-pathways of TCDCA. It pointed out the direction for further research on anti-inflammatory mechanism of TCDCA.

Changes in subfoveal choroidal thickness after intravitreal injections of ranibizumab for macular edema secondary to retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the changes in subfoveal choroidal thickness ( SFCT ) after intravitreal injections of ranibizumab ( IVR ) for macular edema secondary to retinal vein occlusion ( RVO) . METHODS:Thirty-six eyes of 36 patients with macular edema secondary to RVO) were treated with 0. 5mg IVR monthly for 3mo and received additional IVR as needed over the following 1a period. SFCT of the all eyes ( the affected eyes with RVO and unaffected fellow eyes ) was measured by enhanced depth imaging optical coherence tomography images before and after the IVR. RESULTS: The mean SFCT of the affected eyes with RVO decreased from 246. 7±115. 0μm at baseline to 220. 5±102.0μm at 1mo (P0. 05), 228. 6±127. 0μm at 6mo (P>0.05), 223.6±101.0μm at 12mo(P>0.05). There were statistically significant difference between affected eyes with RVO and unaffected fellow eyes. CONCLUSION: The SFCT is decreased after IVR for macular edema secondary to RVO. IVR seems to affect the hemorheology of the choroid.

Mitochondrial network in the heart

Mitochondria are subcellular organelles that provide energy for the cell. They form a dynamic tubular network and play an important role in maintaining the cell function and integrity. Heart is a powerful organ that supplies the motivation for circulation, thereby requiring large amounts of energy. Thus, the healthiness of cardiomyocytes and mitochondria is necessary for the normal cardiac function. Mitochondria not only lie in the center of the cell apoptotic pathway, but also are the major source of reactive oxygen species (ROS) generation. Mitochondrial morphological change includes fission and fusion that are regulated by a large number of proteins. In this review we discuss the regulators of mitochondrial fission/fusion and their association with cell apoptosis, autophagy and ROS production in the heart.

The wave of first-order kernel and second-order kernel of multifocal electroretinogram stimulated with LED / 眼科

Objective To investigate the waveform of the first-order kernel and second-order kernel of muhifocal electroretinogram stimulated with light emitting diode(LED).Design Prospective,noncomparative,interventional case series.Participant 18 subjects(18 eyes)who had been accepted the mfERG test.Method The patients were devided into two groups,they accepted the muhifocal elec- troretinogram(mfERG)stimulated with cathode ray tube(CRT)and LED using the Roland RETI Scan3.15 system.The first-order kernel or the second-order kernel was analyzed.The stimulation time of LED were changed from 1.7ms to 16.7ms.Five different stimulation time of LED in this study were 1/10(1.7ms),3/10(5ms),5/10(8.3ms),7/10(ll.7ms)and 10/10(16.7ms).Main Outcome Measure The summed responses were observed.The waveform,amplitude and implicit times of mfERG summed response were analyzed.Result The waveforms of the first-order kernel stimulated by LED were similar to those of CRT.In the second-order kernels of mfERG,the wave- forms were obviously different from those stimulated by LED and CRT.The P1 wave stimulated by CRT was sharp,but the P1 wave of LED was broad.The N2 wave of LED was deeper.The amplitude of N1 wave and P1 wave were increased,and their implicit times pro- longed with the stimulation times prolonging.Conclusion In the first-order kernel of mfERG,the waveform of the summed response stimulated by LED was similar to that of LED.In the second-order kernel of mfERG,the waveform stimulated by LED was more com- plicated,may be there were more inner retina information.(Ophthalmol CHN,2006,15:351-355)

Studies on mechanism of antiasthmatic and anti-inflammatory actions of CDCA / 中国中药杂志

<p><b>OBJECTIVE</b>To observe antiasthmatic and anti-inflammatory actions mechanisms of CDCA.</p><p><b>METHOD</b>The content of NO was determined by method of nitroreductase chromatometry in serum and trachea tissue. The content of cAMP was analysed by method of competitive protein-binding assay. The content of PGE2 was determined by method of ultraviolet spectrophotometry.</p><p><b>RESULT</b>CDCA significantly decreased the content of NO of serum and trachea tissue in mice. CDCA increased greatly the content of cAMP of trachea tissue in rats. CDCA significantly decreased the content of PGE2 of trachea and lung tissue in mice.</p><p><b>CONCLUSION</b>Mechanisms of antiasthmatic and anti-inflammatory actions of CDCA are related to increasing the content of cAMP in trachea tissue and decreasing the constituent of NO and PGE2 in body.</p>