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.

Effects of titanium dioxide nanoparticles and lipopolysaccharide on antioxidant function of liver tissues in mice / 北京大学学报(医学版)

OBJECTIVE@#To compare the effects of different sized titanium dioxide (titanium dioxide, TiO2) on the antioxidant function of liver tissues in mice, and study the effect of TiO2 nanoparticles on the susceptibility of lipopolysaccharide (LPS) on liver tissues.@*METHODS@#Ninety 4-week-old clean-grade male ICR mice were divided into 18 groups, in which the mice were fed for different feed involving ordinary feed, nanometer TiO2 feed which meant the feed including 1% (mass fraction) TiO2 nanoparticles, and submicron TiO2 feed which meant the feed including 1% (mass fraction) TiO2 submicron particles. Respectively, they were fed for 1 month, 3 months and 6 months. On the second day after the feeding, respectively, 0 and 10 mg/kg LPS were given by gavage. The mice were harvested after 4 h and the body weight and liver weight for calculating the liver coefficient were recorded. Then the liver tissue homogenates were prepared for determining the antioxidant indexes including the total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA).@*RESULTS@#The change of body weight in mice was only discovered in group fed for 1 month, which showed significant decrease of body weight in treatment groups compared with control group. And there was no significant change of the liver coefficient in each group. Compared with control groups, nanometer TiO2 groups and submicron TiO2 group, the activity of T-AOC, T-SOD and MDA of nanometer TiO2+LPS group and submicron TiO2+LPS group in which the mice were fed for 1 month and 6 months increased in different degree. And another result was also existing. The MDA activity of liver in different sized treatment groups fed for 3 months decreased. Neither significant difference between the results of different sized TiO2 treatment groups, nor significant difference among different sized TiO2 groups and the control groups were observed.@*CONCLUSION@#Longterm peroral TiO2 nanoparticles and TiO2 submicron particles are more likely to cause damage to the liver in the growing mice, and the damage may be either reductive or oxidative. In addition, small sized TiO2 can increase the susceptibility of mice liver to LPS and the susceptibility will increase with the increase of exposure time.

Clinical study on endoscopic closure of gastrointestinal fistula using the over-the-scope-clip system / 医学研究生学报

Objective Gastrointestinal fistula is a serious complication after operation. It is reported that the over-the-scope-clip(OTSC) can close intestinal full-thickness wall and treat gastrointestinal fistula effectively. This study was to investigate the efficacy of OTSC in the treatment of gastrointestinal fistula.Methods We analyzed the clinical data of 28 postoperative patients with gastrointestinal fistula who underwent endoscopic closure using OTSC in Endoscopy Center of Research Institute of General Surgery in our hospital from October 2014 to October 2017, and recorded the course of disease, the site of gastrointestinal fistula, the diameter of fistula and the efficacy of OTSC. Patients with successful closure were followed up for half a year after hospital discharge to observe the recurrence of fistula.Results Endoscopic closure with OTSC was successful in all the 28 patients without complications like bleeding and falling off. In the sinus tract or digestive tract radiography at 1-2 weeks after OTSC closure, 23 patients were successful in endoscopic closure(82.14%). In the six months′ follow-up of 23 patients with successful treatment, 4 patients were lost to follow-up and 19 patients were successful without recurrence of fistula.Conclusion The endoscopic closure of gastrointestinal fistula using OTSC is safe and effective, avoiding reoperation and reducing trauma.

Expression of proteins in serum and hippocampus after closed brain injury in rats / 法医学杂志

OBJECTIVE@#To explore the difference of expression of proteins between the serum and hippocampus after brain injury in rats.@*METHODS@#Male SD rats were used to establish brain injury model. The changes of proteins expression profile in serum and hippocampus at different time after brain injury were analyzed using weak cationic exchanger (WCX2) chips and immobilized metal affinity capture arrays-Cu (IMAC-Cu) chips by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.@*RESULTS@#A total of 436 protein peaks were detected in serum and 346 protein peaks were detected in hippocampus using WCX2 chips. A total of 229 protein peaks were detected in serum and 345 protein peaks were detected in hippocampus using IMAC-Cu chips. The same 10 protein peaks were respectively detected in serum and hippocampus using WCX2 chips. The same 13 protein peaks were respectively detected in serum and hippocampus using IMAC-Cu chips.@*CONCLUSION@#The changes of protein expression profile in serum and hippocampus are obvious after closed brain injury and show a significant difference. The different proteins detected in serum and hippocampus using the same chip could be biochemical markers for determining brain injury.

Proteomic changes in cerebral cortex of neonatal rats with experimental congenital hypothyroidism / 中华儿科杂志

<p><b>OBJECTIVE</b>To screen differentially expressed brain proteins with proteomic method in cerebral cortex of neonatal rats with congenital hypothyroidism.</p><p><b>METHOD</b>From the 13th day of gestation, pregnant Wistar rats from the experimental group were given intragastrically with 2.5 ml of 1% propylthiouracil daily. Cerebral cortex specimens were collected from the control and hypothyroidism neonatal rats. Two-directional electrophoresis (2-DE) was applied to analyze protein expression diversities between the euthyroid and hypothyroidism neonatal rat cerebral cortex. Protein spots with significantly different expression were screened and identified by mass spectrometry. Radioimmunoassay (RIA) was used to analyze serum FT(3), FT(4) levels of each groups.</p><p><b>RESULT</b>The body weight of hypothyroid neonatal rats were lower than those in the corresponding control group (t = -8.07, P < 0.01). The FT(3) levels of hypothyroid neonatal rats were lower than those in the corresponding control group (t = 5.39, P < 0.01). The FT(4) levels of hypothyroid neonatal rats were lower than those in the corresponding control group (t = 7.62, P < 0.01). Stable 2-DE maps of normal and CH neonatal rat were constantly obtained. The maps were analyzed by software. Seven protein spots with high reproducibility, high resolution and significantly different expression were chosen and identified by mass spectrometry, including collapsing response mediator protein 2, actin related protein 2/3 complex subunit 5, ubiquitin-conjugating enzyme E2-25K, ATP synthase subunit d, Cu-Zn superoxide dismutase, synuclein alpha, and nucleoside diphosphate kinase.</p><p><b>CONCLUSION</b>The value of this research is demonstrated here by the identification of several proteins known to be associated with nerve synapse structures formation, cell survival, metabolism, cell signal transduction, neural differentiation and nerve growth in the central nervous system. Furthermore this study identified several proteins except for collapsing response mediator protein 2 and Cu-Zn superoxide dismutase that have not previously been described in the literature and which may play an important role as either sensitive biomarkers of brain dysfunction caused by congenital hypothyroidism. In congenital hypothyroidism, brain development retardation may be related with some important processes, including abnormal synaptic formation, excess ROS production and apoptosis. The above-mentioned proteins may play critical roles in the processes, which provide valuable clues to clarify the pathogenesis of brain developmental disorders induced by congenital hypothyroidism.</p>

The study in primary cultured astrocytes following fluid percussion injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the morphology alterations and proteomics changes in primary astrocytes following fluid percussion injury.</p><p><b>METHODS</b>Primary cultures of astrocytes were prepared from cerebral hemispheres of 1-3 d-old SD rats, then, astrocytes were randomly divided into control group and injury group which were subjected to (0.2 +/- 0.01) MPa fluid percussion injury. The changes of protein expression pattern in astrocytes between injury and control groups were monitored with two dimensional gel electrophoresis.</p><p><b>RESULTS</b>Astrocytes' s abnonmalities of morphology after injury were apparent. The fluid percussion injury caused astrocytes edema, shrinkage, cell junction disconnection and necrosis at 2 h after injury. 24 h and 48 h after injury, most part of astrocytes's dendrites and soma became hypertrophy and showed a higher rate of cell proliferation. The dynamic proteomics changes were identified and total different 13 spots were detected in this study from the 2DE gels. The different displayed 5 spots were identified via MALDI-TOF: cofilin 1, destrin, phosphoglycerate mutase 1, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10, annexin 1.</p><p><b>CONCLUSION</b>The obvious alteration of morphology and protein expression pattern in primary cultured astrocytes could be induced after fluid percussion injury. The differential proteins detected were probably related to stress responses.</p>

Detection of distinct proteins for brain injury rats serum using a protein chip / 中国应用生理学杂志

<p><b>AIM</b>To explore the alteration of serum protein fingerprinting of rats subjected brain injury.</p><p><b>METHODS</b>Male Sprague-Dawley rats were randomly divided into seven groups, ie, normal control group, sham operation group, injury 4 h, 8 h, 12 h, 24 h and 48 h groups. The change of protein pattern in serum was monitored with weak cationic exchanger chip and surface-enhanced laser desorption ionization-time of flight-mass spectrometry.</p><p><b>RESULTS</b>The reduction of 5648 Da protein expression was detected at 4 h, 8 h or 12 h after injury (P < 0.01, compared with control and sham operation) and recovery at 24 h or 48 h. The increase of 9681 Da protein expression was detected at 4 h, 8 h or 12 h after injury (P < 0.05, compared with control and sham operation) and recovery at 24 h or 48 h.</p><p><b>CONCLUSION</b>The alteration of protein expression in serum could be induced after brain injury.</p>

The expression of growth hormone release factor gene carried with PLGA microspheres in muscle tissue and its effect on mouse growth / 生物工程学报

Injectable sustained-release pcDNA3-GRF (1-32) microspheres were prepared by double emulsion-in liquid evaporation process,using biodegrable poly lactic-co-glycolic acid as carrier. The enrapment efficiency, mean particle size, drug content thus prepared were 69%, 2.20 microm, 8% and 70% respectively. The result of transfection in vivo showed that after 30 days, accumulative increased body weights on the group injected with pcDNA3-GRF (1-32) microspheres was significantly higher than those group injected with naked plasmid (12.87%), plasmid-empty microspheres (19.72%) and saline (58.58%) respectively. PCR and RT-PCR showed that the expression level of GRF gene on the group injected with pcDNA3-GRF (1-32) microspheres was the highest. GRF gene released by microspheres was still detected after 30 days. In conclusion, pcDNA3-GRF (1-32) microspheres have a controlled release effect and GRF gene could be successfully transfected into muscle cells of mouse by microspheres with higher efficacy and stronger biological function.

C-mycprotein expression upregulated by 2-(3-estrone-N-ethyl piperazine-methyl) tetracycline in bone / 药学学报

<p><b>AIM</b>To study the effect of XW630 on expression of pro-oncogene c-myc in the long bones of fetal mice in vitro for postulating the mechanism by which XW630 exerts its effect on bone.</p><p><b>METHODS</b>The fetuses of pregnant mice were removed on day 16 of gestation, the long bones of the forelimbs of female fetal mice were freed of muscle and soft tissue and cultured in a specific device for 48 h in BGJb medium treated with 1 x 10(-7), 1 x 10(-8) and 1 x 10(-9) mol.L-1 XW630 in the final medium. After cultured for 48 h, the long bones were harvested and immunohistochemical analysis was performed for determination of c-Myc protein expression in epiphyseal plates. The areas of positive cells in the resting zone, proliferative zone and hypertrophic zone in epiphyseal plate were determined under image analytic system.</p><p><b>RESULTS</b>When the concentration of XW630 in the medium was 1 x 10(-9) mol.L-1, the area of c-Myc positive cells increased in the proliferative zone compared with 1 x 10(-9) mol.L-1 in the estrone group, significant increase was also observed in the resting zone compared with the control group. When the concentration of XW630 in medium was 1 x 10(-8) or 1 x 10(-7) mol.L-1, stronger expression than that in the control group and the estrone group at the same concentration was observed in each of the three zones.</p><p><b>CONCLUSION</b>The estrogenic effect of XW630 on bone was stronger than that of estrone. XW630 may promote proliferation and differentiation of chondroncytes by promoting c-Myc protein expression in chondroncytes. Thus, endochondral bone formation was enhanced.</p>

Underground Part-Obturated Environment and Human Health / 环境与健康杂志

Objective To observe the effect of underground part-obturated environment on human health. Methods 12 testees were chosen to undergo the experiment of 6 days in the part-obturated situation. The microclimate blood routine immunological items and the symptoms were investigated. Results In the part-obturated environment the average temperature was 15.2 ℃ the humidity was 75.5% the velocity of the wind was 0.06 m/s. Among the testees one was found had higher WBC number three had higher lymphocytes number. During the experiment the average value of CD3+ CD8+ and B cell were 60.05% 26.04% and 10.41% respectively the NK cell was higher compared with the controlbefore the experiment the differences were significant P