Protective role of brain CYP2J in diverse Parkinson disease animal models / 中国药理学与毒理学杂志

OBJECTIVE CYP2 family including CYP2C and CYP2J is the predominant arachidonic acid (AA) epoxygenase, and the epoxidation of AA produces four regioisomeric cis-epoxyeicosatrienoic acids (5,6-, 8,9-, 11,12-, and 14,15-EET). Human CYP2J2 is one of the main CYP isoforms expressed in brain, but CYP2C8 was present at a low level. The aim of this study is to investigate the roles of brain CYP2J in Parkinson disease. METHODS Rats received the right-unilaterally injection with concentrated LV-CYP2J3 or LV-EGFP in the substantia nigra (SN) at 3 d before LPS or 6-OHDA treatment. The animals were tested for rotational behavior with the dopaminergic agonist apomorphine dissolved in sterile saline at 14 and 21 d after LPS injection. The influence of CYP2J-dependent derivative, 14,15-EET, on the genes related with oxidative stress was assayed in SH-SY5Y cells. RESULTS CYP2J overexpression or 14,15-EET treatment significantly increased the levels of SOD1, CAT, GPX1, NRF2 and KEAP1 in neurons. TLR4- MyD88 signaling pathway was involved the down- regulation of CYP2J by LPS. The binding of p-CREB with the promoter of CYP2J was inhibited by the LPS treatment. The loss of dopami?nergic neurons in the right SN induced by LPS or 6- OHDA was significantly decreased by CYP2J3 transfection at 21 d after LPS injection. Compared with LPS or 6-OHDA group, the number of the rotation of rats was decreased by 42.6% and 60.7% by CYP2J3 transfection at 14 d after LPS or 6-OHDA injection;meanwhile, the rotation number was decreased by 12.7% and 21.3% at 21 d. The accumulation of alpha synuclein induced by LPS was significantly decreased by CYP2J3 transfection. The mRNA levels of SOD1, CAT, GPX1, NRF2 and KEAP1 in SN were decreased by LPS, which was attenuated by the injection of LV-CYP2J3. CONCLUSION Brain CYP2J can play a protective role in the damage of the inflammation and oxidative stress to the dopaminergic neurons. Brain CYP2J- dependent derivatives from AA may have therapeutic effects in Parkinson disease via the up- regulation of the antioxidant system in neurons.

Analysis of the efficacy of three treatment options for cesarean scar pregnancy management.

AIM: To assess three different methods in treating patients with cesarean scar pregnancy (CSP). METHODS: We evaluated pre-, intra- and postoperative conditions of 124 CSP patients in one of the three treatment groups, of which 37 patients underwent uterine curettage by hysteroscopy under ultrasound monitoring (group 1), 28 patients were treated with methotrexate followed by hysteroscopy (group 2) and 59 cases underwent uterine arterial embolization followed by hysteroscopy (group 3). The treatment options were determined based on the patients' conditions. RESULTS: Among all three groups, group 3 (uterine arterial embolization followed by hysteroscopy) had the least intraoperative blood loss and the highest success rate with curettage, but the highest hospitalization cost. Group 1 (only hysteroscopy) had the shortest length of hospitalization and the lowest cost, but the highest intraoperative blood loss and slowest recovery. Group 2 (methotrexate followed by hysteroscopy) had the longest period of hospitalization, and other indexes had fallen in between the other two groups. CONCLUSION: Among the three methods, uterine arterial embolization followed by hysteroscopy is the safest and most efficient method without considering the cost of hospitalization. Patients with a low level of ß-hCG may consider choosing hysteroscopy under ultrasound monitoring or methotrexate followed by hysteroscopy. The advantage is low cost of hospitalization; however, patients may be under relatively higher surgical risks and lower first time surgical success rate, especially for patients treated by hysteroscopy under ultrasound monitoring.

The antitumor effect of the toll-like receptor 3 ligand polyinosinic-cytidylic acid as an adjuvant.

Although polyinosinic-polycytidylic acid (poly(I:C)) has been applied in tumor immunity as a Toll-like receptor 3 (TLR3) ligand, the interaction between poly(I:C) and TLR3 is still unclear, as are the mechanisms underlying the antitumor effect of poly(I:C). Our aim was to investigate the interaction between poly(I:C) and TLR3, as well as the mechanisms underlying the antitumor effect of poly(I:C). NK92 cells were maintained in medium (untreated group), or medium containing E7(44-62) (E7 group) or E7(44-62)+poly(I:C) (poly(I:C)/E7 group), and we measured the expression of TLR3 mRNA, p-p65, and IκB-α protein. The cells were first incubated in medium alone or medium containing TLR3 monoclonal antibody, and then in medium containing poly(I:C)/E7. Finally, we measured the level of interferon-beta (INF-ß) in the supernatant and determined the tumor cell-killing effect of the NK92 cells. At 1 h, the expression of TLR3 mRNA in the poly(I:C)/E7 group was markedly higher than that in the untreated and E7 groups (P < 0.05). When compared with the poly(I:C)/E7 group, the expression of IκB-α was dramatically increased in the E7 and untreated groups, and the expression of p-p65 was dramatically decreased in the E7 and untreated groups (all P < 0.05). At 24 h, INF-ß content and tumor cell-killing activity in the poly(I:C)/E7 group were markedly higher than those in the untreated group (P < 0.001, <0.05, respectively). Treatment with TLR3 monoclonal antibody significantly inhibited poly(I:C)/E7-induced INF-ß secretion and tumor cell-killing activity in NK92 cells (P < 0.001, <0.05, respectively). The interaction between poly(I:C) and TLR3 plays an important role in the antitumor immunity of NK92 cells. In addition, the interaction between poly(I:C) and TLR3 increases INF-ß expression, which may be attributed to the activation of NFκB.

Is an idea different from cake: can you have it and eat it, too? A violation of permanence in information consumption.

One of the basic features of information is permanence. This feature states that the consumption of information by one consumer does not affect the availability of that information to other consumers. We present examples in two studies indicating that both laymen and experts of information exchange may be motivated to make choices that violate the permanence feature in accepting (Study 1) and offering (Study 2) information. When they possess, but have not yet consumed information, people may suffer from the appearance of wastefulness. This apparent wastefulness may provide a potential explanation for the observed violation of the permanence feature. Our findings indicate that, as the material age evolves into the information age, information-exchange behavior has not evolved significantly away from material-exchange behavior.