Dieckol exerts anticancer activity in human osteosarcoma (MG-63) cells through the inhibition of PI3K/AKT/mTOR signaling pathway

BackgroundOsteosarcoma (OS) is the most common malignant bone cancer with more metastasis and increased occurrence in children and teen-agers and being responsible for more number of morbidity and mortality worldwide.ObjectiveThe current exploration was planned study the in vitro anticancer actions of dieckol against human OS MG-63 cells via PI3K/AKT/mTOR signaling inhibition.MethodologyThe cytotoxicity of dieckol was scrutinized by MTT assay. Effects of dieckol on the ROS accumulation, apoptotic cell death, and MMP level in the MG-63 cells were studied by respective fluorescence staining assays. The levels of proliferative, inflammatory, and apoptotic markers in the dieckol treated MG-63 cells were scrutinized by marker specific kits. The expressions of PI3K, AKT, and mTOR was assayed by RT-PCR.ResultsThe MTT assay revealed that the dieckol dose dependently prevented MG-63 cells viability and the IC50 was found at 15 µM. Dieckol treatment effectively reduced the MMP level and improved the ROS generation and apoptosis in MG-63 cells. Dieckol also regulated the proliferative (cyclin D1), inflammatory (COX-2, IL-6, TNF-α, and NF-κB), and apoptotic (caspase-3, Bax, Bcl-2) markers in the MG-63 cells. The PI3K/AKT/mTOR signaling in the MG-63 cells were effectively inhibited by the dieckol treatment.ConclusionIn conclusion, our findings from this study recommends that the dieckol could be a talented anticancer candidate for the OS management in the future.     

普氏原羚分布、种群和保护现状

普氏原羚(Procapra przewalskii)是青藏高原特有物种, 为了掌握该物种的分布和种群状况, 我们于2014-2015年采用全面调查和直接计数的方法, 对普氏原羚的分布、种群和保护现状进行了调查。结果如下: 普氏原羚分布在青海湖周边12个隔离的分布点, 与全国第一次野生动物资源调查的结果相比, 有多个新的分布点被发现, 分布范围和面积扩大; 调查共发现1,238只普氏原羚, 与2010年以后的调查结果相比, 种群数量维持在一个稳定的水平。然而, 仅有4个分布点位于青海湖国家级自然保护区范围内。尽管刚察县成立了青海湖普氏原羚特护区, 天峻县成立了普氏原羚自然保护站, 但现有的管护力度仍然不够, 且缺乏系统的管理规划。我们建议在天峻县布哈河上游的生格-快尔玛地区成立普氏原羚自然保护区; 同时建立适当的生态补偿机制, 协调保护与社区发展的矛盾; 鉴于目前圈养种群发展迅速, 建议在历史分布区选取合适的地点进行人工繁育个体的迁地放归。     

P300 binds to and acetylates MTA2 to promote colorectal cancer cells growth

MTA2 is a member of metastasis associated family, which is highly expressed in several solid tumors and associated with tumor cells migration and invasion. Here, we report that MTA2 is acetylated at K152 and histone acetyltransferase p300 binds to and acetylates MTA2. Furthermore, mutation of the MTA2 acetylation site inhibits the growth of colorectal cancer cells and migration and invasion of Rat1 fibroblasts. These results reveal a novel post-translational regulation of MTA2 by the way of p300-dependent acetylation, which is important for tumor cells growth and migration and provides a potential target for clinical cancer research.     

Inhibition of 26S protease regulatory subunit 7 (MSS1) suppresses neuroinflammation

Recently, researchers have focused on immunosuppression induced by rifampicin. Our previous investigation found that rifampicin was neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In this study, using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we discovered that 26S protease regulatory subunit 7 (MSS1) was decreased in rifampicin-treated microglia. Western blot analysis verified the downregulation of MSS1 expression by rifampicin. As it is indicated that the modulation of the ubiquitin-26S proteasome system (UPS) with proteasome inhibitors is efficacious for the treatment of neuro-inflammatory disorders, we next hypothesized that silencing MSS1 gene expression might inhibit microglial inflammation. Using RNA interference (RNAi), we showed significant reduction of IkBα degradation and NF-kB activation. The production of lipopolysaccharides-induced pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide, cyclooxygenase-2, and prostaglandin E(2) were also reduced by MSS1 gene knockdown. Taken together, our findings suggested that rifampicin inhibited microglial inflammation by suppressing MSS1 protein production. Silencing MSS1 gene expression decreased neuroinflammation. We concluded that MSS1 inhibition, in addition to anti-inflammatory rifampicin, might represent a novel mechanism for the treatment of neuroinflammatory disorders.     

Prediction of Nodal Involvement in Primary Rectal Carcinoma without Invasion to Pelvic Structures: Accuracy of Preoperative CT,MR, and DWIBS Assessments Relative to Histopathologic Findings

Objective

To investigate the accuracy of preoperative computed tomography (CT), magnetic resonance (MR) imaging and diffusion-weighted imaging with background body signal suppression (DWIBS) in the prediction of nodal involvement in primary rectal carcinoma patients in the absence of tumor invasion into pelvic structures.

Methods and Materials

Fifty-two subjects with primary rectal cancer were preoperatively assessed by CT and MRI at 1.5 T with a phased-array coil. Preoperative lymph node staging with imaging modalities (CT, MRI, and DWIBS) were compared with the final histological findings.

Results

The accuracy of CT, MRI, and DWIBS were 57.7%, 63.5%, and 40.4%. The accuracy of DWIBS with higher sensitivity and negative predictive value for evaluating primary rectal cancer patients was lower than that of CT and MRI. Nodal staging agreement between imaging and pathology was fairly strong for CT and MRI (Kappa value = 0.331 and 0.348, P<0.01) but was relatively weaker for DWIBS (Kappa value = 0.174, P<0.05). The accuracy was 57.7% and 59.6%, respectively, for CT and MRI when the lymph node border information was used as the criteria, and was 57.7% and 61.5%, respectively, for enhanced CT and MRI when the lymph node enhancement pattern was used as the criteria.

Conclusion

MRI is more accurate than CT in predicting nodal involvement in primary rectal carcinoma patients in the absence of tumor invasion into pelvic structures. DWIBS has a great diagnostic value in differentiating small malignant from benign lymph nodes.