The role of lncRNA OIP5-AS1 in cancer development and progression

OIP5-AS1, a conserved lncRNA, has been reported to be involved in several biological and pathological processes, including oncogenesis. OIP5-AS1 exerts its oncogenic or antitumor functions via regulation of different miRNAs in various cancer types. In this review, we describe the dysregulation of OIP5-AS1 expression in a variety of human cancers. Moreover, we discuss the multiple functions of OIP5-AS1 in cancer, including in proliferation, apoptosis, autophagy, ferroptosis, cell cycle, migration, metastasis, invasion, epithelial to mesenchymal transition, angiogenesis, cancer stem cells and drug resistance. Furthermore, we provide a future perspective for OIP5-AS1 research. We conclude that targeting OIP5-AS1 might be a promising cancer therapy approach.

     

Suitability of UK Biobank Retinal Images for Automatic Analysis of Morphometric Properties of the Vasculature

PurposeTo assess the suitability of retinal images held in the UK Biobank - the largest retinal data repository in a prospective population-based cohort - for computer assisted vascular morphometry, generating measures that are commonly investigated as candidate biomarkers of systemic disease.MethodsNon-mydriatic fundus images from both eyes of 2,690 participants - people with a self-reported history of myocardial infarction (n=1,345) and a matched control group (n=1,345) - were analysed using VAMPIRE software. These images were drawn from those of 68,554 UK Biobank participants who underwent retinal imaging at recruitment. Four operators were trained in the use of the software to measure retinal vascular tortuosity and bifurcation geometry.ResultsTotal operator time was approximately 360 hours (4 minutes per image). 2,252 (84%) of participants had at least one image of sufficient quality for the software to process, i.e. there was sufficient detection of retinal vessels in the image by the software to attempt the measurement of the target parameters. 1,604 (60%) of participants had an image of at least one eye that was adequately analysed by the software, i.e. the measurement protocol was successfully completed. Increasing age was associated with a reduced proportion of images that could be processed (p=0.0004) and analysed (p<0.0001). Cases exhibited more acute arteriolar branching angles (p=0.02) as well as lower arteriolar and venular tortuosity (p<0.0001).ConclusionsA proportion of the retinal images in UK Biobank are of insufficient quality for automated analysis. However, the large size of the UK Biobank means that tens of thousands of images are available and suitable for computational analysis. Parametric information measured from the retinas of participants with suspected cardiovascular disease was significantly different to that measured from a matched control group.     

Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and the Risk of Head and Neck Cancer

Aim

To evaluate the association between the EPHX1 Tyr113His and His139Arg polymorphisms in the EPHX1 gene and the risk of head and neck cancer.

Materials and Methods

Studies on the association of EPHX1 Tyr113His and His139Arg polymorphisms with HNC performed up until June 1st, 2014, were identified using a predefined search strategy. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of these associations.

Results

In this meta-analysis, 10 case-control studies, which included 9 studies of Tyr113His (1890 cases and 1894 controls) and 10 studies of His139Arg polymorphisms (1982 cases and 2024 controls), were considered eligible for inclusion. Overall, the pooled results indicated that the EPHX1 Tyr113His polymorphism was significantly associated with increased HNC risk (Tyr/His vs. Tyr/Tyr, OR = 1.26, 95%1.02–1.57;His/His+ Tyr/His vs. Tyr/Tyr, OR = 1.29, 95% I = 1.03–1.61). However, no significant association was found between the His139Arg polymorphism and HNC risk. In the subgroup analysis, a statistically significant association between the EPHX1 Tyr113His polymorphism and HNC was observed in population-based case-control studies (PCC), which involved less than 500 participants and genotype frequencies in HWE. This association showed minimal heterogeneity after excluding studies that were determined to contribute to heterogeneity. After categorizing the studies by publication time, a sensitivity analysis and cumulative meta-analysis of the two associations were conducted, and the results of the two analyses were consistent.

Conclusion

Our meta-analysis suggests that EPHX1 Tyr113His polymorphism may be a risk factor for HNC, while the EPHX1 His139Arg polymorphism has no association with HNC risk.     

Copper and manganese induce yeast apoptosis via different pathways

Metal ions are essential as well as toxic to the cell. The mechanism of metal-induced toxicity is not well established. Here, for the first time we studied two essential nutritional elements, copper and manganese, for their apoptotic effects in yeast Saccharomyces cerevisiae. Although beneficial at subtoxic levels, we demonstrated that at moderately toxic levels, both metals induce extensive apoptosis in yeast cells. At even higher concentrations, necrosis takes over. Furthermore, we investigated the molecular pathways mediating Cu- and Mn-mediated apoptotic action. Mitochondria-defective yeast exhibit a much reduced apoptotic marker expression and better survival under Cu and Mn stress, indicating mitochondria are involved in both Cu- and Mn-induced apoptosis. Reactive oxygen species (ROS) are generated in high amounts in Cu- but not in Mn-induced cell death, and Cu toxicity can be alleviated by overexpression of superoxide dismutase 2, suggesting ROS mediate Cu but not Mn toxicity. Yeast metacaspase Yca1p is not involved in Cu-induced apoptosis, although it plays an important role in the Mn-induced process. A genetic screen identified Cpr3p, a yeast cyclophilin D homologue, as mediating the Cu-induced apoptotic program. Cpr3p mutant seems to eliminate Cu-induced apoptosis without affecting ROS production, while leaving necrosis intact. These results may provide important insight into a detailed understanding at the molecular and cellular level of metal toxicity and metal accumulation diseases.     

Evaluation of Environmental Safety Concentrations of DMSA Coated Fe(2)O(3)-NPs Using Different Assay Systems in Nematode Caenorhabditis elegans

Dimercaptosuccinic acid (DMSA) coating improves the uptake efficiency presumably by engendering the Fe(2)O(3)-NPs. In the present study, we investigated the possible environmental safety concentrations of Fe(2)O(3)-NPs using different assay systems in nematode Caenorhabditis elegans with lethality, development, reproduction, locomotion behavior, pharyngeal pumping, defecation, intestinal autofluorescence and reactive oxygen species (ROS) production as the endpoints. After exposure from L4-larvae for 24-hr, DMSA coated Fe(2)O(3)-NPs at concentrations more than 50 mg/L exhibited adverse effects on nematodes. After exposure from L1-larvae to adult, DMSA coated Fe(2)O(3)-NPs at concentrations more than 500 μg/L had adverse effects on nematodes. After exposure from L1-larvae to day-8 adult, DMSA coated Fe(2)O(3)-NPs at concentrations more than 100 μg/L resulted in the adverse effects on nematodes. Accompanied with the alterations of locomotion behaviors, ROS production was pronouncedly induced by exposure to DMSA coated Fe(2)O(3)-NPs in the examined three assay systems, and the close associations of ROS production with lethality, growth, reproduction, locomotion behavior, pharyngeal pumping, defecation, or intestinal autofluorescence in nematodes exposed to DMSA coated Fe(2)O(3)-NPs were confirmed by the linear regression analysis. Moreover, mutations of sod-2 and sod-3 genes, encoding Mn-SODs, showed more susceptible properties than wild-type when they were used for assessing the DMSA coated Fe(2)O(3)-NPs-induced toxicity, and the safety concentrations for DMSA coated Fe(2)O(3)-NPs should be defined as concentrations lower than 10 μg/L in sod-2 and sod-3 mutant nematodes.     

鹿茸多肽药理作用研究

鹿茸多肽(PAP)是从鹿茸中提出的含有促进骨和软骨细胞分裂的各种多肽因子。离体实验表明,PAP(10～50μg/ml)对离体培养的家兔肋软骨和人胚关节软骨以及鸡胚头盖骨成骨样细胞都有很强的促进有丝分裂作用。整体实验表明,PAP对大鼠挠骨骨折有明显促愈合作用;对大鼠背部皮肤缺损有加速修复作用;对大鼠后肢骨折处骨髓巨噬细胞吞噬功能有促进作用;但对大鼠角叉菜胶性足肿胀和小鼠二甲苯性耳廓肿胀均无抗炎症作用。     

Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and is involved in chronological aging

Apoptosis-inducing factor (AIF) and AIF-homologous mitochondrion-associated inducer of death (AMID) are both mitochondrial flavoproteins that trigger caspase-independent apoptosis. Phylogenetic analysis suggests that these two proteins evolutionarily diverge back from their common prokaryote ancestor. Compared with AIF, the proapoptotic nature of AMID and its mode of action are much less clarified. Here, we show that overexpression of yeast AMID homologue internal NADH dehydrogenase (NDI1), but not external NADH dehydrogenase (NDE1), can cause apoptosis-like cell death, and this effect can be repressed by increased respiration on glucose-limited media. This result indicates that the regulatory network of energy metabolism, in particular the cross-talk between mitochondria and the rest of the cell, is involved in Ndi1p-induced yeast cell apoptosis. The apoptotic effect of NDI1 overexpression is associated with increased production of reactive oxygen species (ROS) in mitochondria. In addition, NDI1 overexpression in sod2 background causes cell lethality in both fermentable and semifermentable media. Interruption of certain components in the electron transport chain can suppress the growth inhibition from Ndi1p overexpression. We finally show that disruption of NDI1 or NDE1 decreases ROS production and elongates the chronological life span of yeast, accompanied by the loss of survival fitness. Implication of these findings for Ndi1p-induced apoptosis is discussed.     

Postnatal changes in the expression of serotonin 2A receptors in various brain stem nuclei of the rat.

Previously, we reported a critical period [around postnatal day (P) 12-13 in the rat] in respiratory network development when distinct neurochemical, metabolic, and physiological changes occur. Since serotonin 2A (5-HT(2A)) receptors play an important role in respiratory modulation, we hypothesized that they may undergo developmental adjustments during the critical period. Semi-quantitative immunohistochemical analyses were conducted in labeled neurons in a number of brain stem nuclei with or without known respiratory functions from P2 to P21 in rats. Our data indicate that the expressions of 5-HT(2A) receptors in neurons of the pre-B?tzinger complex, the nucleus ambiguus, and the hypoglossal nucleus were maintained within a relatively narrow range between P2 and P21, with a dip at P3-P4 and a significant reduction only at P12. This change was not observed in the nonrespiratory cuneate nucleus. These results suggest that reduced expressions of 5-HT(2A) receptors at P12 contributes to neurochemical imbalance within brain stem respiratory nuclei at that time and may be involved in decreased hypoxic ventilatory response at this critical period of development.