Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Transmembrane domain dependent inhibitory function of FcγRIIB

FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of FcγRIIB is also indispensable for its inhibitory function. Indeed, recent epidemiological studies revealed that a non-synonymous single nucleotide polymorphism (rs1050501) within the TM domain of FcγRIIB, responsible for the I232T substitution, is associated with the susceptibility to systemic lupus erythematosus (SLE). In this review, we will summarize these epidemiological and functional studies of FcγRIIB-I232T in the past few years, and will further discuss the mechanisms accounting for the functional loss of FcγRIIB-I232T. Our review will help the reader gain a deeper understanding of the importance of the TM domain in mediating the inhibitory function of FcγRIIB and may provide insights to a new therapeutic target for the associated diseases.

Effect of nerve growth factor on changes of myelin basic protein and functional repair of peripheral nerve following sciatic nerve injury in rats / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury.</p><p><b>METHODS</b>The sciatic nerves of rats were injured by sectioning with shaver,and divided into 3 groups: NGF group (Group A), group of normal saline solution (Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD-4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP.</p><p><b>RESULTS</b>The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B (P<0.05). The MEP was elicited in 76% of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP-positive cells in the Group A than in the Group B in one and four weeks respectively.</p><p><b>CONCLUSIONS</b>NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.</p>

Experimental study on the apoptosis of the astrocytes and the oligodendrocytes induced by Ca(2+) reperfusion / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the apoptosis rules of the astrocytes and oligodendrocytes induced by Ca(2+) reperfusion.</p><p><b>METHODS</b>The apoptosis of purified cultured astrocytes and oligodendrocytes induced by Ca(2+) reperfusion and the relationship between the development of the cell apoptosis and post-reperfusion time was observed.</p><p><b>RESULTS</b>Both the astrocytes and oligodendrocytes were obviously in a time-dependent fashion, and the apoptosis ratios of the oligodendrocytes (39.73%+/-4.16%) were higher than the astrocytes (19.64%+/-4.67%) 24 hours after Ca(2+) reperfusion. The TUNEL positive cells were 13.6+/-1.82 and 21.4+/-1.95 at every visual field of astrocytes and oligodendrocytes respectively 24 hours after Ca(2+) reperfusion.</p><p><b>CONCLUSIONS</b>The astrocytes and oligodendrocytes are similar wi th the development rules on apoptosis and have different susceptiveness to the situation.</p>

Pathological changes of Vessels Following Experimental Anastomosis with Large Blood Vessel Anastomat / 第三军医大学学报

The thoracic aorlae of 39 goats and the inferior venae cavae of 9 goats were anastomosed experimentally with the Large Blood Vessel Anastomat. The pathological changes of these vessels were observed dynamically within one year after the operation. It was found that the Large Blood Vessel Anastomat was rather effective. The vessels anastomosed with this instrument showed a better result than those anastomosed with manual suture.