1. X Wu, W Guo, L Wu, Y Gu, L Gu, S Xu, X Wu, Y Shen, Y Ke, R Tan, Y Sun*, Q Xu*. Selective sequestration of STAT1 in the cytoplasm via phosphorylated SHP-2 ameliorates murine experimental colitis. J Immunol 2012, 189(7): 3497-3507. (*share correspondence-authorship) 

Highlight: The side effects of current immunosuppressive drugs have impeded the development of therapies for immune diseases. Selective regulation of STAT signaling is an attractive strategy for treating immune disorders. This paper used a small-molecule compound fusaruside to explore possible means of targeting STAT1 for the treatment of Th1-mediated inflammation. The fusaruside-induced ability of pY-SHP-2 to selectively sequestrate STAT1 from recruitment to IFN-γ receptor is independent of its function as a phosphatase, demonstrating a novel role for SHP-2 in regulating both STAT1 signaling and Th1-type immune responses. These findings could lead to increased options for the treatment of Crohn’s disease and other Th1-mediated inflammatory diseases.

2. W Guo, W Liu, S Hong, H Liu, C Qian, Y Shen, X Wu, Y Sun*, Q Xu*. Mitochondria-dependent apoptosis of Con A-activated T lymphocytes induced by asiatic acid for preventing murine fulminant hepatitis. PLoS ONE 2012; 7(9): e46018. (*share correspondence-authorship)

Highlight: Selectively  facilitating  apoptosis  of  activated  T  cells  is  essential  for  the  clearance  of  pathogenic  injurious  cells  and subsequent efficient resolution of inflammation. However, few chemicals have been reported to trigger apoptosis of activated T cells for the treatment of hepatitis without affecting quiescent T cells. This study reported that asiatic acid, a natural triterpenoid, selectively triggered apoptosis of concanavalin A (Con A)-activated T cells in a mitochondria-dependent manner. Taken together, our results demonstrated that the ability of asiatic acid to induce apoptosis of activated T cells and its potential use in the treatment of T-cell-mediated inflammatory diseases.

3. W Li, R Song, X Fang, L Wang, W Chen, P Tang, B Yu, Y Sun*, Q Xu*. SBF-1, a synthetic steroidal glycoside, inhibits melanoma growth and metastasis through blocking interaction between PDK1 and AKT3. Biochem Pharmacol 2012; 84: 172-181. (*share correspondence-authorship) 

Highlight: This paper demonstrate that SBF-1, a synthetic steroidal glycoside, has a strong antitumor activity against melanoma cells in vitro and in vivo. Its mechanism underlying such antitumor effect is related to the blockage of the interaction between PDK1 and AKT3.

4.XF Wu, XX Wu, WJ Guo, Q Luo, YH Gu, Y Shen, RX Tan, Y Sun*, Q Xu*. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice via inducing apoptosis of activated T lymphocytes. Toxicol Appl Pharma 2012; 263: 296-302. (*share correspondence-authorship)

Highlight: This paper aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation.

5. XX Wu, Y Sun*, WJ Guo, YH Gu, XF Wu, Y Shen, RX Tan, Q Xu*. Rebuilding the balance of STAT1 and STAT3 signalings by fusaruside, a cerebroside compound, for the treatment of T cell-mediated fulminant hepatitis in mice. Biochem Pharmacol, 2012; 84: 1164-1173. (*share correspondence-authorship)

Highlight: Dysregulation of signal transducer and activator of transcription (STAT) signaling is usually associated with intricate immune diseases and rebuilding the balance of STAT1 and STAT3 signalings is being explored as a useful approach for the treatment of these diseases. However, few chemicals have been reported to rebuild the balance of these two signalings for immune hepatitis therapy. This study reported that fusaruside, a new kind of cerebroside isolated from an endophytic fungus Fusarium sp. IFB-121 in Quercus variabilis, significantly ameliorated concanavalin A (Con A)-induced T cell-mediated fulminant hepatitis in mice through rebuilding the balance of STAT1 and STAT3 signaling. These results suggest that fusaruside is potentially useful for the treatment of T cell-mediated human liver disorders.

6.H Liu, R Xu, L Feng, W Guo, N Cao, C Qian, P Teng, L Wang, X Wu, Y Sun, J Li, Y Shen, Q Xu. A novel chromone derivative with anti-inflammatory property via inhibition of ROS-dependent activation of TRAF6-ASK1-p38 pathway. PLoS ONE 2012; 7(8): e37168.

Highlight: The p38 MAPK signaling pathway plays a pivotal role in inflammation. Targeting p38 MAPK may be a potential strategy for the treatment of inflammatory diseases. In the present  study, we show that a novel chromone derivative, DCO-6, significantly reduced lipopolysaccharide (LPS)-induced inflammation. Blockade of the upstream events required for p38 MAPK action by DCO-6 may provide a new therapeutic option in the treatment of inflammatory diseases.

7. W Guo, W Liu, G Chen, S Hong, C Qian, N Xie, X Yang, Y Sun*, Q Xu*. Water-soluble andrographolide sulfonate exerts anti-sepsis action in mice through down-regulating p38 MAPK, STAT3 and NF-κB pathways. Int Immunopharmcaol, 2012; 14: 613-619. (*share correspondence-authorship)

Highlight: Andrographolide is a prescribed drug used for preventing and treating the common cold, influenza, viral infections or allergies. However, its poor water solubility enormously limits its bioavailability. This study aimed at examining and comparing the effect of andrographolide sulfonate (trade name: Xi-Yan-Ping Injection), a water-soluble form made from andrographolide through sulfonating reaction, on the treatment of murine sepsis model induced by lipopolysaccharide (LPS). These results reveal that andrographolide sulfonate ameliorates sepsis in mice through suppressing p38 MAPK, STAT3 and NF-κB pathways and suggest that andrographolide sulfonate has an advantage of andrographolide for the treatment of endotoxin shock.


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