there is growing evidence that 5 HT3 receptor polymorphisms subscribe to individual drug response but replication studies are needed. Curiously, in more recent years, a genetic and neurophysiological overlap is postulated between affective disorders, schizophrenia and Cathepsin Inhibitor 1 autism on the one hand and neurogastrointestinal disorders and psychiatric conditions on the other hand. There is no doubt that variation in central and peripheral 5 HT mediated signal pathways plays a role in the pathophysiology of the complicated problems. This is in keeping with the pilot studies we reference in this review. First functional brain imaging studies established the significance of polymorphisms in neural networks of brain areas associated with mental processes and knowledge and learning, as also stated. We consequently draw the conclusion an specific 5 HT3 receptor constitute specifically modulates neural circuits strongly related pain and cognition/emotion perception and therefore makes people more susceptible to these problems. Further studies are warranted to reproduce first findings to organization. Cellular differentiation Pharmacogenetic studies assessing genotypes and 5 HT3 antagonist reaction might date=june 2011 a relationship and allow an individualised therapy later on. Neuroimaging studies and pharmacogenetic techniques concentrating on disease appropriate neural networks will unravel this function of 5 HT3 receptors in these complex issues. 5 HT3 receptor activation by its physiological ligand 5 HT results in cation influx through the open ion channel, which causes depolarisation of the cell. Currently, a selection of selective 5 HT3 agonists including phenylbiguanide and chlorophenylbiguanide exists. Due to their emetogenic and anxiogenic qualities, 5 HT3 agonists have no therapeutic potential. In contrast, 5 HT3 antagonists are currently the gold-standard to deal with CINV. Besides substances which have been built to target 5 HT3 receptors there are also people from various compound classes that Enzalutamide manufacturer are able to modulate 5HT3 receptor function. In this section, we shall concentrate on the impact of these substances including drugs as well as endogenous and natural substances on 5 HT3 receptor function and resulting pathophysiological or therapeutical implications. On the basis of the construction of 5 HT and the non selective antagonist cocaine, bemesetron and tropisetron were created while the first selective high-affinity 5 HT3 antagonists. Currently, the materials tropisetron, ondansetron, granisetron, dolasetron, palonosetron, ramosetron and azasetron are available to take care of CINV and PONV with the latter two being qualified only in the Far East.

The involvement of 5 HT3 receptors in vomiting legislation and emesis is more developed and 5 HT3 antagonists would be the gold standard in treatment of chemotherapy induced nausea and vomiting. A pharmacogenetic review of cancer patients treated with 5 HT3 antagonists addressing this issue found no association of SNPs in with CINV, however, the removal c. 104 102delAGA was seen to be related to CINV. While people carrying the WT allele showed the bottom score, patients homozygous for the deletion had the highest score of vomiting and nausea purchase Lenalidomide after therapy with 5 HT3 antagonists. Identification of individuals carrying the deletion by genotyping could give rise to a different and better hospital treatment of these individuals. In another study, no relationship of this variant to CINV could possibly be found, however the variant p. K163N was strongly related to vomiting. This indicated that the 5 HT3C subunit plays a part in the pathogenesis of CINV. Moreover, a plan in, p. G36A, was recently found to be nominally related to vomiting in the same cohort of patients. Polymorphisms in the genes may consequently serve as predictors for CINV, yet replication in larger study cohorts is anticipated from the scientific community. Postoperative sickness and nausea are unpleasant side effects of general anaesthesia. The genetic effect Skin infection of the 5 HT receptor system to the development of sickness and vomiting has over and over repeatedly been offered. A pilot study confirmed genetic variations in and to become associated with the individual risk of developing PONV. The extent of their functional effect on PONV or whether there’s a functional impact at all couldn’t be answered in this study. Most of the variations found did not reside within the protein coding region of the gene but regulatory effects on mRNA splicing or balance cannot be ignored. Sickness and throwing up are also a concomitant phenomenon during pregnancy. The frequency of nausea and vomiting in pregnancy is approximately 70?80% with as much as 2000 suffering from serious symptoms. Critical throwing up in pregnancy Crizotinib clinical trial continues to be associated with considerable maternal morbidity, micronutrient lack, Wernicke encephalopathy, oesophageal tears and even death. 5 HT3 antagonists have been proven to be effective in treating NVP without increase in the price of miscarriages or malformation in humans. Up to now, these drugs represent a powerful treatment alternative for women with severe symptoms who don’t respond to the usual treatment. The contribution of 5 HT3 receptor polymorphisms in the pathogenesis of NVP has been addressed by a retrospective study. Two SNPs in, rs6807670 and rs6806362, were found to be connected with pregnancy-related sickness. The authors figured distinct subgrouping of expectant mothers experiencing NVP according to the genotype of associated versions may enable individualised antiemetic medication as time goes by.

results also showed attention dependent savings by SB216763 treatment in both mRNA levels and protein expression of IL 6, TNF and IL 1 in LPS stimulated MC3T3 E1 cells, further determining that GSK 3 chemical may prevents the inflammatory reaction in infected osteoblasts. In agreement with this findings, Natsume et al. showed that lithium chloride, another inhibitor of GSK 3, significantly repressed IL 6 release in TNF induced MC3T3 E1 cells. To date, relatively little Afatinib 439081-18-2 information is available about the effect of GSK 3 chemical on modulating the immune actions of osteoblasts. We offer crucial evidence supporting the speculation that the GSK 3 inhibitor might repress the activity of osteoblasts and hence get anti inflammatory potential in inflammatory bone diseases. Moreover, there is a particular meaning to study the anti inflammatory effect of GSK 3 chemical in contaminated osteoblasts. It is recognized that inflammatory bone infection are characterized by local inflammatory response and bone loss, which are caused by pathological bacteria colonization. Gathering evidences have indicated that GSK 3 inhibitors may effectively induce osteoblast differentiation Cellular differentiation in vitro and increase bone mass in vivo. Taken together with our studies, GSK 3 might represent a novel therapeutic target for bone inflammatory disease, with dual roles in promoting bone formation as well as suppressing inflammatory reaction. Thus, it’s of great importance to clarity the regulatory system of GSK 3 inhibitor in infected osteoblasts. It is well-recognized that CD40 is really a tumor necrosis factor receptor superfamily member with predominant service through the NF B signaling pathway. Several lines of evidence show that the service of the NF T has a critical role in up controlling CD40 gene expression subsequent LPS stimulation in dendritic cells, macrophages, and other non immune cell types. But, along with the NF T signaling, increasing current facts suggest that the expression of CD40 can be controlled through a system involving the activation of the STAT 1 signaling pathway. Qin and colleagues suggested that LPS induces CD40 expression supplier JZL184 in macrophages and microglia at the transcriptional level and requires activation of the transcription factors NF W and STAT 1. Equally, Lam and colleagues demonstrated Leptin alone or in cooperation with LPS stimulate CD40 expression through the activation of transcription activators, STAT 1 and NF Bp65, to target the promoter. Our results are in agreement with your previous results showing that LPS stimulation induces the activation of NF W and STAT 1.However, the effects of GSK 3 inhibition on modulating those activities of the 2 signaling pathways are completely different.

Rac1 phrase construct sequences transporting the Q61L and T17N strains and a Rac activity assay kit were purchased from Upstate. Briefly, RAW 264. 7 macrophages were cultured in 6 cm dishes. After reaching confluence, cells were treated with the vehicle and PGN, or pre-treated with specific inhibitors as indicated followed closely by PGN. After incubation, cells were washed twice in ice-cold phosphate buffered saline and deubiquitination assay solubilized in extraction buffer containing 10mM Tris, 140mM NaCl, 2mM PMSF, 5mM DTT, 0. 50-year NP 40, 0. 05mM pepstatin A, and 0. 2mM leupeptin. Samples of equal amounts of protein were subjected to SDS PAGE, then transferred onto a polyvinylidene fluoride membrane whichwas then incubated in TBST buffer containing five minutes non-fat milk. Proteins were visualized by distinct primary antibodies and then incubated with horseradish peroxidase or alkaline phosphataseconjugated secondary antibodies. Immunoreactivity was detected using enhanced chemiluminescence or NBT/BCIP following the manufacturers directions. Quantitative data were obtained using a densitometer with Image Pro Plus image analysis pc software programs. RAW 264. 7 cells were grown in 6 cm dishes. After reaching confluence, cells were treated with 30 g/ml PGN for your indicated time intervals or pretreated with certain inhibitors as indicated accompanied by PGN. After incubation, cells were washed twice with ice cold PBS, lysed in 1 ml of lysis buffer containing 20mM Tris HCl, 1mM MgCl2, 125mM Cholangiocarcinoma NaCl, 10 percent Triton X100, 1mM PMSF, 10 g/ml leupeptin, 10 g/ml aprotinin, 25mM glycerophosphate, 50mM NaF, and 100 M sodium orthovanadate, and centrifuged at 14,000 g for 30min. The beads were washed three times with lysis buffer and two times with kinase buffer containing 20mM MgCl2, 20mM HEPES, and 2mM DTT, and centrifuged at 8000 g for 5 min. The reactions were performed by incubating immunoprecipitated beads with 20 m of kinase buffer supplemented with 50 g/ml of histone H2B, 20 M ATP, and 3 Ci of ATP at 30 C for 30 min. Twenty microliters of the reaction mixtureswas analyzed by 15-week Ganetespib manufacturer SDS PAGE followed by autoradiography. Rac activity was measured utilizing a Rac activity assay system. The assay was performed in line with the manufacturers directions. Shortly, cells were washed twice with ice-cold PBS and lysed in 1ml of magnesium lysis buffer, 150mM NaCl, five full minutes lgepal CA 630, 10mM MgCl2, 5mM EDTA, 10 % glycerol, 10 g/ml aprotinin, and 10 g/ml leupeptin and centrifuged at 14,000 g for 30min. Lysate was incubated with 5 g of PAK1 p21 binding site agarose at 4 C over night. The beads were centrifuged at 8000 g for 5 min and washed three times with MLB lysis buffer. Destined Rac proteins were then solubilized in 20 m of 2 Laemmli sample buffer and quantitatively detected by Western blotting utilizing mouse monoclonal anti Rac together with the ECL system.

In a reaction to cytokine deprivation or cellular damage by UV irradiation, BimEL and BimL are released from the dynein motor complex, allowing them to bind and translocate to Bcl 2 like survival facets. At least for apoptosis induced by cytokine treatment, BimL and BimEL look like more crucial than BAD. In contrast to BAD mice, Bim mice show an extreme accumulation of cells that depend on cytokines for their survival such as macrophages, lymphocytes and granulocytes. Cathepsin Inhibitor 1 Furthermore, Bim lymphocytes and neurons are resistant to cytokine withdrawal in culture. However, since other aspect dependent cell types such as erythrocytes don’t accumulate in Bim rats, still another BH3 only protein such as BAD may cooperate with Bim to sense cytokine starvation signs. Exactly why is Bim sequestered to the dynein motor complex of microtubules and maybe not to other cellular scaffolds? Since DCL1/LC8 is in large excess over Bim, it seems unlikely the BH3 only protein regulates the microtubule motor protein in healthier cells. By contrast, some Metastatic carcinoma apoptotic stimuli including cytokine removal use a pressure on the microtubular system that is then thought by Bim. Similarly, taxol, a microtubule polymerizing drug may trigger the release of Bim from LC8 and its relationship with Bcl 2/Bcl xL. Thus, by being bound to an essential macromolecular structure such as the microtubules, Bim is ideally placed to become a stress indicator and communicator of the stress signal to the multidomain Bcl 2 proteins. Because Bim is produced together with DLC1, we think that post translational modification of components of the dynein motor complex that usually bind DLC1 unleash Bim. Such a choice could be the cyclin dependent protein kinase CDK5. Recently, the idea of cytoskeletal sequestration is identified with another BH3 just protein, called Bmf. Instead of being bound to microtubules, this protein interacts with the dynein light chain of the actin cytoskeleton (-)-MK 801 centered myosin V motor complex in healthier cells. Their release from this interaction and complex with Bcl xL and Bcl 2 isn’t triggered by cytokine elimination but by having less the treatment and extracellular matrix with drugs which depolymerize actin. Again, as for Bim, Bmf is released along with DLC2 suggesting a change of components of the myosin V engine to which DLC2 is bound in healthy cells. Such a modification might be achieved by enzymes that influence myosin V function such as calmodulin kinase of the cystein protease calpain. Bim, and possibly also Bmf, are nevertheless not merely regulated by alterations in subcellular localization but also by transcriptional induction, the same as Noxa/PUMA and EGL 1. As an example, Bim is just a powerful killer in thymocytes, and Bouillet et al. Demonstrate that TCR causing of thymocytes advances the expression of Bim by about three fold.

The perfect solution is structure of Bax is quite similar to that of Bcl 2 like survival facets. As in Bcl 2 and Bcl xL, a hydrophobic pocket is formed by the BH1 BH3 domains in to which a peptide from still another protein might bind. The N terminus is relatively non structured, and while a BH4 area was initially not expected by the amino acid sequence, the general orientation Fostamatinib molecular weight of the equivalent location in Bax with respect to the remaining protein is identical to that in Bcl xL. A vital distinction between Bcl xL and Bax can be found in the place. In Bax, this helix is less packed for the hydrophobic core than in Bcl xL. This causes it to be easier for the domain to rotate about its axis to expose the remains from the hydrophobic core, making them accessible for binding to the hydrophobic lines of Bcl 2 like survival factors. This freedom of the BH3 domain is crucial for the professional apoptotic activity of Bax like elements since trading this region from Bax to Bcl 2 changed Bcl 2 to a death agonist despite the existence of the BH4 region. Yet another difference involving the construction of Bax and Bcl 2/Bcl xL is the fact that the former may be established having its hydrophobic membrane anchoring C terminus. Why was this possible? All three proteins are located on intracellular membranes because of hydrophobic C final transmembrane domain which mediates both membrane targeting Infectious causes of cancer and membrane insertion. Perhaps, the C termini of Bcl xL and Bcl 2 are exposed to solvent immediately after protein synthesis, and they consequently must be immediately targeted to membranes in order to prevent protein clustering and precipitation. By comparison, the C terminal tail of Bax is folded back in the hydrophobic pocket of the compound in an identical way as the Bak BH3 peptide binds to Bcl xL, except that the directional perception of the peptide is opposite to that of the C terminal helix of Bax. By this process, Bax is prevented from binding to membranes in addition to to other proteins, and releasing the C terminus ubiquitin conjugation can provoke both mitochondrial targeting and conversation with essential pro apoptotic binding partners. Nevertheless, mitochondrial re-distribution of Bax does not only occur in apoptotic cells as has recently been postulated. Subcellular localization studies of many different cell types in tissues and in culture revealed that even though Bax is very abundant in the cytosol of tissues, it’s equally distributed between mitochondria and the cytosol in most cultured cells. This suggests that there should be a mobile protein or a post translational modification which causes the unleashment of the C terminus and the targeting of Bax to mitochondria when cells are transferred from areas to in vitro cultures. On the basis of the design of Bax, we propose that this type of element could liberate the C terminus by fighting at the hydrophobic pocket.

finding indicates that there is an increase in NADPH consumption, and that is in all probability necessary for GSH synthesis. It really is well known that imatinib is metabolized via conjugation with GSH catalyzed by glutathione S transferase enzymes. Hence, met inhibitor GSH accumulation may possibly have an effect on imatinib catabolism as well as this kind of other biological functions as intracellular signaling. In actual fact, GSH has an effect on activation of anti apoptotic MAP kinase and NF ?B signaling. Interestingly, NAD H:quinone oxidoreductase is one of the proteins that we observed to get under expressed in KCL22R cells. Nqo2 is actually a cytosolic flavoprotein that carries out the two electron reduction of quinones applying electron donors such as nicotinamide riboside and it is known to get involved in the metabolic activation and/or detoxification of xenobiotics, whilst its precise physiological part remains uncertain. Chemical proteomic profiling in K562 CML cells confirmed many recognized imatinib targets including Abl and Src kinases, and recognized the receptor tyrosine kinase DDR1, which is associated with tumor progression and metastasis, and oxidoreductase Nqo2 as novel targets of imatinib.

Another study showed that Nqo2 is bound and inhibited by imatinib in K562 cells and in CML sufferers. On the other hand, the effect of Nqo2 binding within the efficacy of imatinib stays unknown. In this context, it truly is conceivable that the differential expression of Nqo2 across Plastid KCL22R and KCL22S cells could influence imatinib metabolism. An additional statistically relevant molecular perform we recognized is associated to translation regulator activity. The human elongation factor1 delta, currently being a translator regulator, is involved in the constructive regulation on the I kappaB kinase/NFkappaB cascade. In imatinib resistant CML individuals, the NF ?B cellular pathway is activated in the Bcr Abl independent fashion.

This pathway, therefore, may be enhanced from the hedgehog pathway inhibitor above expression of EEF1D, as shown on this paper. To characterize the molecular networks that involve the proteins identified on this research, we analyzed our data working with IPA program. Examination of network one exhibits that a number of differentially expressed proteins are connected with Erk signaling. The Raf/MEK/ERK pathway influences chemotherapeutic drug resistance. We discovered that the level of phosphorylated Erk 1/ two is higher in KCL22R cells than in KCL22S cells. This suggests that activation of Erk occurred in KCL22R cells, in line by using a study exhibiting that the Bcr Abl independent activation of Erk 1/2 might contribute to imatinib resistance in K562 cells. Network 1 includes many tension response and chaperone proteins. Specifically, the heat shock proteins Hsp70, Hsp60, Hsp27 and Grp78 are differentially expressed in KCL22R and KCL22S cells.

Mechanisms through which signaling by aberrantly activated ALK cooperates with MYCN overexpression to boost neuroblastoma development stay undefined, posing a major obstacle to the development of effective focused treatments for this devastating disease. We’ve created a transgenic zebrafish model by which overexpression of human MYCN within the PSNS causes tumors within the fish analog of the adrenal medulla that closely resemble human neuroblastoma. Applying this type system, we initiated studies to discover mechanistically the relationship (-)-MK 801 between MYCN overexpression and mutationally triggered ALK during neuroblastoma pathogenesis in the PSNS. We first isolated a 5. 2 kb promoter fragment upstream of the coding sequence of the dopamine b hydroxylase gene, which encodes the rate limiting enzyme for noradrenalin activity. This fragment was utilized to drive expression of enhanced green fluorescent protein in a stable zebrafish transgenic line, Tg, given DbH in this article. In juvenile and adult transgenic zebrafish, EGFP was particularly expressed by sympathetic neurons of the superior cervical ganglia, the first sympathetic ganglion to build up in early embryogenesis, and by each constant segmental ganglion of the sympathetic chain. EGFP was Retroperitoneal lymph node dissection also indicated by sympathoadrenal cells of the interrenal gland, the zebrafish equivalent of the human adrenal gland. In the interrenal gland, the EGFP expressing cells could be visualized inside a distinct area in the ventral aspect of the head kidney, intermixed with adrenal cortical cells that are TH and EGFPnegative. The uniqueness of EGFP expression for sympathoadrenal cells when influenced by the dbh promoter fragment is confirmed by coexpression of endogenous TH, another molecule expressed by chromaffin cells and sympathetic nerves. Zebrafish Expressing MYCN Develop Neuroblastoma Using a coinjection technique, we produced a stable transgenic zebrafish point, Tg, given MYCN in this specific article, that overexpresses the human MYCN order Avagacestat gene fused to EGFP under control of the dbh promoter. In MYCN transgenic fish the growth of cells as tumors created expressing EGFP was readily detectable in living fish by immunofluorescence microscopy. EGFP tumor masses were present in the anterior stomach, akin to the interrenal gland, and were composed of small, undifferentiated, spherical tumor cells with hyperchromatic nuclei, usually forming nests. Cyst cells were strongly immunoreactive for TH and the neuronal markers Synaptophysin and Hu, indicating their PSNS related neuronal origin. Regular interrenal chromaffin cells also expressed TH, but not Hu or Synaptophysin, indicating the neuroblastomas arose from sympathetic neuroblast precursors and not chromaffin cells, as may be the case in human neuroblastoma.

Ase1 GFP partially colocalized with Spc29 CFP in 78% of smallbudded cells with unseparated SPBs and was not detectable within the remaining cells. Whilst this staining may well reflect Ase1 localization to your intranuclear MTs, it isn’t doable to immediately determine whether Ase1 localizes to the SPBs or even the nuclear MTs in these cells since the nuclear MTs are quick before spindle assembly. Regardless, the visual appeal of Ase1 temporally precedes SPB separation, consistent using a purpose for Ase1 in spindle assembly. We next analyzed Ase1GFP Anastrozole ic50 in ipl1 315 cells and discovered that, in contrast to 78% on the wild style cells, it was only noticeable in 54% on the ipl1 315 little budded cells. Ipl1 for that reason regulates the localization of Ase1 on the time of spindle assembly, consistent with these proteins acting collectively to regulate spindle assembly. Bipolar spindle assembly is vital for chromosome segregation and necessitates the action of your BimC kinesins, a conserved family of plus end motor proteins.

In budding yeast, the Cin8 and Kip1 BimC kinesins act in parallel Papillary thyroid cancer spindle assembly pathways, with Cin8 creating the main contribution to spindle assembly. Right here we report that the Ipl1 protein kinase along with the spindle midzone protein Ase1 also grow to be crucial for spindle assembly while in the absence of Cin8. A Separation of Perform Allele Reveals a Function for Ipl1/Aurora in Spindle Assembly Remarkably, our evaluation on the ipl1 315 allele that is lethal during the absence of cin8 established that it truly is proficient in all of the previously recognized MT based mostly functions of Ipl1. Whilst cin8 mutants arrest in mitosis on account of spindle checkpoint activation, the inviability of cin8 ipl1 315 cells was not because of a lack of checkpoint action. As an alternative, cin8 ipl1 315 double mutants arrest with duplicated but unseparated SPBs.

The requirement for Ipl1 to assemble spindles in c-Met kinase inhibitor the absence of Cin8 just isn’t one of a kind to ipl1 315 because the ipl1 321 mutation is also lethal with cin8 mutants. On the other hand, to our knowledge this is the very first instance of an ipl1 mutant which is particularly defective in just one of the regarded Ipl1 functions. Ipl1 315 is made up of a single mutation within the catalytic domain, primary to decreased kinase action. Due to the fact Ipl1315 also exhibited a decreased interaction with its activator, Sli15, we propose the altered interaction leads for the reduction in Ipl1 kinase exercise. We have been stunned the reduction in kinase exercise did not have an impact on other Ipl1 functions, given that all other mutants we have now studied also have decreased kinase activity.

On the other hand, Ipl1 315 retains 2 fold a lot more kinase activity than Ipl1 321, suggesting that better amounts of Ipl1 kinase exercise are necessary for its spindle assembly perform than for its other functions, quite possibly resulting from a limiting substrate.

it can activate mononuclear and dendritic cells to start the anti viral defense and stop the apoptosis of virus-infected cells. Liver fibrosis and its finish stage cirrhosis represent the ultimate common pathways of practically all chronic liver diseases. Today, for your functions of Treg and Th17 cells throughout HBV disease Cathepsin Inhibitor 1 and their intrinsic developing links, the importance of Treg/Th17 balance is often discussed in CHB pathogenesis. Under situations, the cytokines and growth facets in microenvironments might stimulate mitogen activated protein kinase pathways in T cells. To date, three different MAPK pathways have been identified in mammalian cells: the extracellular signal regulated kinase pathway, the h Jun amino terminal kinase pathway and the p38 MAPK pathway. Recent studies have implicated that phosphatidylinositide 3 kinase /AKT pathway activation can be a essential requirement for T cell proliferation and cell cycle progression. PI3K/AKT and mapk/erk pathways are crucial in transferring extracellular concept via membrane destined ligands, transmembrane receptors and cytoplasmic Metastatic carcinoma secondary messengers into cell nucleus, ergo controlling the gene expression that controls many important cellular processes including cell proliferation and apoptosis are important objectives for antifibrogenic treatments. Glycyrrhizin, the main active component of licorice root, is often used in Asia to take care of patients with chronic hepatitis. GL could promote cell growth of hepatocytes therefore it could be utilized to aid liver regeneration after liver damage. Besides, GL have anti viral, anti cancer and immunomodulatory capabilities. In individuals with chronic hepatitis C, intravenous administration of GL can decrease lcd aminotransaminase degrees, therefore preventing following hepatocellular carcinoma as well as liver fibrosis progression. Our previouswork had shown purchase Enzalutamide that GL could prevent hepatotoxin induced liver damage and cirrhosis via inhibition of NF kappaB binding activity, cell proliferation and collagen production of HSCs. However, the activity of GL hasn’t been completely elucidated in liver fibrosis. Here this study was made both in vivo and in vitro to research whether GL might regulate CD4 T-cell response via PI3K/AKT, ERK and JNK transmission pathways in mouse liver fibrosis models. Six or eight week-old female BALB/c rats weighing 18?20 g were obtained from the Shanghai Laboratory Animal Centre and maintained under specific pathogen free conditions with a 12-hour light/dark cycle and allowed free access to water and food. Concanavalin An and glycyrrhizin were obtained from Sigma Chemical Co. and dissolved in pyrogen free phosphate buffered saline and saline, respectively.