RETRACTED ARTICLE: Relationship between inflammatory cytokines and risk of depression,and effect of depression on the prognosis of high grade glioma patients

Journal of Neuro-Oncology - Depression is found to be associated with up-regulation of inflammatory cytokines. However, the relationship in high grade glioma (HGG) patients is still unclear. In...     

胡椒碱胶囊自乳化释药系统的处方筛选及体外质量评价

摘 要 目的： 研究胡椒碱自乳化释药系统的处方及其体外特性。方法: 通过溶解度、处方配伍试验以及伪三元相图的绘制来筛选处方,并考察空白处方、含药处方对自乳化效率的影响以及自乳化后乳滴的粒度分布,考察了胡椒碱自乳化胶囊的溶出速率和稳定性。结果: 胡椒碱自乳化胶囊的最终处方为油酸乙酯、Tween 80、Transcutol P,三者之比为30∶55∶15（w∶w∶w）,药物为辅料总量的2.5%,粒径约为90 nm,胡椒碱自乳化胶囊60 min溶出度是自制的胶囊剂6倍;低温和常温稳定性考察药物含量无明显变化。结论:所制备的胡椒碱自乳化胶囊自乳化效率高、能力强、性质稳定,体外溶出率高。     

The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice

AIM:To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE^+/- mice (AChE knockout mice) of various ages.METHODS:Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 μmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE^+/- mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer.RESULTS:Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE^+/- mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE^+/- mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05).CONCLUSION:In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.     

Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Pharmaceutical Research - Antigens were conjugated on the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles to induce systemic and mucosal immune responses after nasal...     

Function of phosphorylation of NF-kB p65 ser536 in prostate cancer oncogenesis

Majority of prostate cancer (PCa) patients carry TMPRSS2/ERG (T/E) fusion genes and there has been tremendous interest in understanding how the T/E fusion may promote progression of PCa. We showed that T/E fusion can activate NF-kB pathway by increasing phosphorylation of NF-kB p65 Ser536 (p536), but the function of p536 has never been studied in PCa. We report here that active p536 can significantly increase cell motility and transform PNT1a cells (an immortalized normal cell line), suggesting p536 plays a critical role in promoting PCa tumorigenesis. We have discovered a set of p536 regulated genes, among which we validated the regulation of CCL2 by p536. Based on all evidence, we favor that T/E fusion, NF-kB p536 and CCL2 form a signaling chain. Finally, PNT1a cells (not tumorigenic) can form tumors in SCID mice when overexpressing of either wild type or active p65 in the presence of activated AKT, demonstrating synergistic activities of NF-kB and AKT signals in promoting PCa tumorigenesis. These findings indicate that combination therapies targeting T/E fusion, NF-kB, CCL2 and/or AKT pathways may have efficacy in T/E fusion gene expressing PCa. If successful, such targeted therapy will benefit more than half of PCa patients who carry T/E fusions.     

Involvement of Ras GTPase-activating protein SH3 domain-binding protein 1 in the epithelial-to-mesenchymal transition-induced metastasis of breast cancer cells via the Smad signaling pathway

In situ models of epithelial-to-mesenchymal transition (EMT)-induced carcinoma develop into metastatic carcinoma, which is associated with drug resistance and disease recurrence in human breast cancer. Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), an essential Ras mediator, has been implicated in cancer development, including cell growth, motility, invasion and apoptosis. Here, we demonstrated that the upregulation of G3BP1 activates the EMT in breast cancer cells. Silencing Smads almost completely blocked this G3BP1-induced EMT, suggesting that this process depends on the Smad signaling pathway. We also found that G3BP1 interacted with the Smad complex. Based on these results, we proposed that G3BP1 might act as a novel co-factor of Smads by regulating their phosphorylation status. Moreover, knockdown of G3BP1 suppressed the mesenchymal phenotype of MDA-MB-231 cells in vitro and suppressed tumor growth and lung metastasis of 4T1 cells in vivo. Our findings identified a novel function of G3BP1 in the progression of breast cancer via activation of the EMT, indicating that G3BP1 might represent a potential therapeutic target for metastatic human breast cancer.     

Targeting protein arginine methyltransferase 5 inhibits colorectal cancer growth by decreasing arginine methylation of eIF4E and FGFR3

Protein arginine methyltransferases (PRMTs) plays critical roles in cancer. PRMT5 has been implicated in several types of tumors. However, the role of PRMT5 in cancer development remains to be fully elucidated. Here, we provide evidence that PRMT5 is overexpressed in colorectal cancer (CRC) cells and patient-derived primary tumors, correlated with increased cell growth and decreased overall patient survival. Arginine methyltransferase inhibitor 1 (AMI-1)strongly inhibited tumor growth, increased the ratio of Bax/Bcl-2, and induced apoptosis in mouse CRC xenograt model. AMI-1 also induced apoptosis and decreased the migratory activity in several CRC cells. In CRC xenografts AMI-1 significantly decreased symmetric dimethylation of histone 4 (H4R3me2s), a histone mark of type II PRMT5, but not the expression of H4R3me2a, a histone mark of type I PRMTs. These results suggest that the inhibition of PRMT5 contributes to the antitumor efficacy of AMI-1. Chromatin immunoprecipitation (ChIP) identified FGFR3 and eIF4E as two key genes regulated by PRMT5. PRMT5 knockdown reduced the levels of H4R3me2s and H3R8me2s methylation on FGFR3 and eIF4E promoters, leading to decreased expressions of FGFR3 and eIF4E. Collectively, our findings provide new evidence that PRMT5 plays an important role in CRC pathogenesis through epigenetically regulating arginine methylation of oncogenes such as eIF4E and FGFR3.