Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria

Hutchinson–Gilford progeria syndrome (HGPS), a fatal premature aging disease, is caused by a single‐nucleotide mutation in the LMNA gene. Previous reports have focused on nuclear phenotypes in HGPS cells, yet the potential contribution of the mitochondria, a key player in normal aging, remains unclear. Using high‐resolution microscopy analysis, we demonstrated a significantly increased fraction of swollen and fragmented mitochondria and a marked reduction in mitochondrial mobility in HGPS fibroblast cells. Notably, the expression of PGC‐1α, a central regulator of mitochondrial biogenesis, was inhibited by progerin. To rescue mitochondrial defects, we treated HGPS cells with a mitochondrial‐targeting antioxidant methylene blue (MB). Our analysis indicated that MB treatment not only alleviated the mitochondrial defects but also rescued the hallmark nuclear abnormalities in HGPS cells. Additional analysis suggested that MB treatment released progerin from the nuclear membrane, rescued perinuclear heterochromatin loss and corrected misregulated gene expression in HGPS cells. Together, these results demonstrate a role of mitochondrial dysfunction in developing the premature aging phenotypes in HGPS cells and suggest MB as a promising therapeutic approach for HGPS.     

广西北海拉关木挥发物的ATD-GC/MS分析及安全性评价

速生红树植物拉关木具有优良的耐盐抗污染特性,但其自身吸收海水污染物后对周边环境及人类是否安全引人关注,尤其是该树种释放的挥发性成分在嗅觉方面是否安全有待评价。该研究以其活体无损伤幼龄及成年枝叶(无花、开花及带果状态)的挥发物为对象,用动态顶空密闭循环吸附捕集方式采集样品后,经全自动热脱附—气相色谱/质谱(ATD-GC/ MS)联用分析。结果表明：拉关木挥发物由萜烯、酮、羧酸等化合物组成,其中萜烯所占比例最高,而最优势成分α-蒎烯在各试样中的相对百分含量均在3/4左右,β-水芹烯、β-蒎烯等其它萜烯也具有较高含量,为10％~15％及在5％以上,萜烯类成分的存在与有关红树植物提取物化学成分的文献报道相吻合。试样中的其它少量成分呈松木、冬青、柑橘、桉树等香韵,部分成分具有中等强度的香比强值(ASV),如莰烯(250)、苯甲醛(500)、苯乙酮(200)、壬醛(550)、水杨酸甲酯(450)等,部分成分的 ASV值较低,如萜品油烯(异松油烯,120)、辛酸(100)、壬酸(100)、对伞花烃(80)等,但对总体气味均有一定的贡献度。由于拉关木挥发物中的各种成分总体有益于人体健康,且在日用香料香精产品中可广泛应用。因此,该树种在嗅觉方面安全、无毒,适合沿海植被恢复、景观及“芳香化”营造等,应用前景良好。     

西洋梨水孔蛋白基因家族的全基因组鉴定及表达分析

水孔蛋白(AQPs,aquaporins)是高效转运水分子的膜内在蛋白,具有丰富的多样性,在调控植物的水分关系中有重要作用。本研究利用西洋梨(Pyrus communis L.‘Bartlett’)基因组数据库,通过生物信息学手段鉴定西洋梨PcAQPs基因家族成员;并利用MEGA 6.0.5软件,采用邻接法构建系统发育树;利用GSDS 2.0软件进行基因结构分析,MEME程序进行Motif分析,AgBase v2.00程序进行GO分析;采用半定量RT-PCR技术研究PcAQPs基因组织表达情况。结果表明,西洋梨基因组中共有54个PcAQPs家族成员,均含有AQP特征结构域和保守的Motif基序,根据基因结构及系统进化分析可分为PIP、TIP、NIP和SIP等4个亚家族。不同基因间结构差别较大,但聚类关系较近的基因其结构类似。GO分析发现,多数PcAQPs基因具有转运蛋白活性,参与物质转运、应激反应、发育和代谢等生物学过程,但不同亚家族成员构成的细胞组分及参与的生物学过程具有明显差异。半定量结果表明,大多数PcAQPs基因在根、茎、叶和果实中均有表达,而且不同基因家族、不同基因间的组织表达模式存在差异。该研究为今后西洋梨PcAQPs基因的克隆和功能分析奠定了基础。     

Cerebral Glioma Grading Using Bayesian Network with Features Extracted from Multiple Modalities of Magnetic Resonance Imaging

Many modalities of magnetic resonance imaging (MRI) have been confirmed to be of great diagnostic value in glioma grading. Contrast enhanced T1-weighted imaging allows the recognition of blood-brain barrier breakdown. Perfusion weighted imaging and MR spectroscopic imaging enable the quantitative measurement of perfusion parameters and metabolic alterations respectively. These modalities can potentially improve the grading process in glioma if combined properly. In this study, Bayesian Network, which is a powerful and flexible method for probabilistic analysis under uncertainty, is used to combine features extracted from contrast enhanced T1-weighted imaging, perfusion weighted imaging and MR spectroscopic imaging. The networks were constructed using K2 algorithm along with manual determination and distribution parameters learned using maximum likelihood estimation. The grading performance was evaluated in a leave-one-out analysis, achieving an overall grading accuracy of 92.86% and an area under the curve of 0.9577 in the receiver operating characteristic analysis given all available features observed in the total 56 patients. Results and discussions show that Bayesian Network is promising in combining features from multiple modalities of MRI for improved grading performance.     

Covered versus Uncovered Self-Expandable Metal Stents for Managing Malignant Distal Biliary Obstruction: A Meta-Analysis

Aim

To compare the efficacy of using covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (UCSEMSs) to treat objective jaundice caused by an unresectable malignant tumor.

Methods

We performed a comprehensive electronic search from 1980 to May 2015. All randomized controlled trials comparing the use of CSEMSs and UCSEMSs to treat malignant distal biliary obstruction were included.

Results

The analysis included 1417 patients enrolled in 14 trials. We did not detect significant differences between the UCSEMS group and the CSEMS group in terms of cumulative stent patency (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.19–4.53; p = 0.93, I² = 0%), patient survival (HR 0.77, 95% CI 0.05–10.87; p = 0.85, I² = 0%), overall stent dysfunction (relative ratio (RR) 0.85, M-H, random, 95% CI 0.57–1.25; p = 0.83, I² = 63%), the overall complication rate (RR 1.26, M-H, fixed, 95% CI 0.94–1.68; p = 0.12, I² = 0%) or the change in serum bilirubin (weighted mean difference (WMD) -0.13, IV fixed, 95% CI 0.56–0.3; p = 0.55, I² = 0%). However, we did detect a significant difference in the main causes of stent dysfunction between the two groups. In particular, the CSEMS group exhibited a lower rate of tumor ingrowth (RR 0.25, M-H, random, 95% CI 0.12–0.52; p = 0.002, I² = 40%) but a higher rate of tumor overgrowth (RR 1.76, M-H, fixed, 95% CI 1.03–3.02; p = 0.04, I² = 0%). Patients with CSEMSs also exhibited a higher migration rate (RR 9.33, M-H, fixed, 95% CI 2.54–34.24; p = 0.008, I² = 0%) and a higher rate of sludge formation (RR 2.47, M-H, fixed, 95% CI 1.36–4.50; p = 0.003, I² = 0%).

Conclusions

Our meta-analysis indicates that there is no significant difference in primary stent patency and stent dysfunction between CSEMSs and UCSEMSs during the period from primary stent insertion to primary stent dysfunction or patient death. However, when taking further management for occluded stents into consideration, CSEMSs is a better choice for patients with malignant biliary obstruction due to their removability.