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排序方式: 共有426条查询结果,搜索用时 15 毫秒
1.
Diego A. Duarte Alexandros Papadimitriou Richard E. Gilbert Kerri Thai Yanling Zhang Mariana A. B. Rosales José B. Lopes de Faria Jacqueline M. Lopes de Faria 《PloS one》2016,11(2)
Bone marrow-derived cells were demonstrated to improve organ function, but the lack of cell retention within injured organs suggests that the protective effects are due to factors released by the cells. Herein, we tested cell therapy using early outgrowth cells (EOCs) or their conditioned media (CM) to protect the retina of diabetic animal models (type 1 and type 2) and assessed the mechanisms by in vitro study. Control and diabetic (db/db) mice (8 weeks of age) were randomized to receive a unique intravenous injection of 5×105EOCs or 0.25 ml thrice weekly tail-vein injections of 10x concentrated CM and Wystar Kyoto rats rendered diabetic were randomized to receive 0.50 ml thrice weekly tail-vein injections of 10x concentrated CM. Four weeks later, the animals were euthanized and the eyes were enucleated. Rat retinal Müller cells (rMCs) were exposed for 24 h to high glucose (HG), combined or not with EOC-conditioned medium (EOC-CM) from db/m EOC cultures. Diabetic animals showed increase in diabetic retinopathy (DR) and oxidative damage markers; the treatment with EOCs or CM infusions significantly reduced this damage and re-established the retinal function. In rMCs exposed to diabetic milieu conditions (HG), the presence of EOC-CM reduced reactive oxygen species production by modulating the NADPH-oxidase 4 system, thus upregulating SIRT1 activity and deacetylating Lys-310-p65-NFκB, decreasing GFAP and VEGF expressions. The antioxidant capacity of EOC-CM led to the prevention of carbonylation and nitrosylation posttranslational modifications on the SIRT1 molecule, preserving its activity. The pivotal role of SIRT1 on the mode of action of EOCs or their CM was also demonstrated on diabetic retina. These findings suggest that EOCs are effective as a form of systemic delivery for preventing the early molecular markers of DR and its conditioned medium is equally protective revealing a novel possibility for cell-free therapy for the treatment of DR. 相似文献
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Gregor Stiglic Petra Povalej Brzan Nino Fijacko Fei Wang Boris Delibasic Alexandros Kalousis Zoran Obradovic 《PloS one》2015,10(12)
Different studies have demonstrated the importance of comorbidities to better understand the origin and evolution of medical complications. This study focuses on improvement of the predictive model interpretability based on simple logical features representing comorbidities. We use group lasso based feature interaction discovery followed by a post-processing step, where simple logic terms are added. In the final step, we reduce the feature set by applying lasso logistic regression to obtain a compact set of non-zero coefficients that represent a more comprehensible predictive model. The effectiveness of the proposed approach was demonstrated on a pediatric hospital discharge dataset that was used to build a readmission risk estimation model. The evaluation of the proposed method demonstrates a reduction of the initial set of features in a regression model by 72%, with a slight improvement in the Area Under the ROC Curve metric from 0.763 (95% CI: 0.755–0.771) to 0.769 (95% CI: 0.761–0.777). Additionally, our results show improvement in comprehensibility of the final predictive model using simple comorbidity based terms for logistic regression. 相似文献
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Shakiru O. Alapafuja Michael S. Malamas Vidyanand Shukla Alexander Zvonok Sally Miller Laura Daily Girija Rajarshi Christina Yume Miyabe Honrao Chandrashekhar JodiAnne Wood Sergiy Tyukhtenko Alex Straiker Alexandros Makriyannis 《Bioorganic & medicinal chemistry》2019,27(1):55-64
Monoacylglycerol lipase (MGL) inhibition provides a potential treatment approach to glaucoma through the regulation of ocular 2-arachidonoylglycerol (2-AG) levels and the activation of CB1 receptors. Herein, we report the discovery of new series of carbamates as highly potent and selective MGL inhibitors. The new inhibitors showed potent nanomolar inhibitory activity against recombinant human and purified rat MGL, were selective (>1000-fold) against serine hydrolases FAAH and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Protein-based 1H NMR experiments indicated that inhibitor 2 rapidly formed a covalent adduct with MGL with a residence time of about 6?h. This interconversion process “intrinsic reversibility” was exploited by modifications of the ligand’s size (length and bulkiness) to generate analogs with “tunable’ adduct residence time (τ). Inhibitor 2 was evaluated in a normotensive murine model for assessing intraocular pressure (IOP), which could lead to glaucoma, a major cause of blindness. Inhibitor 2 was found to decrease ocular pressure by ~4.5?mmHg in a sustained manner for at least 12?h after a single ocular application, underscoring the potential for topically-administered MGL inhibitors as a novel therapeutic target for the treatment of glaucoma. 相似文献
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Alexandros?KanterakisEmail author Jo?l?Kuiper George?Potamias Morris?A.?Swertz 《Source code for biology and medicine》2015,10(1):14
Background
Today researchers can choose from many bioinformatics protocols for all types of life sciences research, computational environments and coding languages. Although the majority of these are open source, few of them possess all virtues to maximize reuse and promote reproducible science. Wikipedia has proven a great tool to disseminate information and enhance collaboration between users with varying expertise and background to author qualitative content via crowdsourcing. However, it remains an open question whether the wiki paradigm can be applied to bioinformatics protocols.Results
We piloted PyPedia, a wiki where each article is both implementation and documentation of a bioinformatics computational protocol in the python language. Hyperlinks within the wiki can be used to compose complex workflows and induce reuse. A RESTful API enables code execution outside the wiki. Initial content of PyPedia contains articles for population statistics, bioinformatics format conversions and genotype imputation. Use of the easy to learn wiki syntax effectively lowers the barriers to bring expert programmers and less computer savvy researchers on the same page.Conclusions
PyPedia demonstrates how wiki can provide a collaborative development, sharing and even execution environment for biologists and bioinformaticians that complement existing resources, useful for local and multi-center research teams.Availability
PyPedia is available online at: http://www.pypedia.com. The source code and installation instructions are available at: https://github.com/kantale/PyPedia_server. The PyPedia python library is available at: https://github.com/kantale/pypedia. PyPedia is open-source, available under the BSD 2-Clause License.6.
7.
Polychronis Kotoglou Alexandros Kalaitzakis Patra Vezyraki Theodore Tzavaras Lampros K. Michalis Francoise Dantzer Jae U. Jung Charalampos Angelidis 《Cell stress & chaperones》2009,14(4):391-406
For many years, there has been uncertainty concerning the reason for Hsp70 translocation to the nucleus and nucleolus. Herein,
we propose that Hsp70 translocates to the nucleus and nucleoli in order to participate in pathways related to the protection
of the nucleoplasmic DNA or ribosomal DNA from single-strand breaks. The absence of Hsp70 in HeLa cells, via Hsp70 gene silencing
(knockdown), indicated the essential role of Hsp70 in DNA integrity. Therefore, HeLa Hsp70 depleted cells were very sensitive
in heat treatment and their DNA breaks were multiple compared to that of control HeLa cells. The molecular mechanism with
which Hsp70 performs its role at the level of nucleus and nucleolus during stress was examined. Hsp70 co-localizes with PARP1
in the nucleus/nucleoli as was observed in confocal studies and binds to the BCRT domain of PARP1 as was revealed with protein–protein
interaction assays. It was also found that Hsp70 binds simultaneously to XRCC1 and PARP-1, indicating that Hsp70 function
takes place at the level of DNA repair and possibly at the base excision repair system. Making a hypothetical model, we have
suggested that Hsp70 is the molecule that binds and interrelates with PARP1 creating the repair proteins simultaneously, such
as XRCC1, at the single-strand DNA breaks. Our data partially clarify a previously unrecognized cellular response to heat
stress. Finally, we can speculate that Hsp70 plays a role in the quality and integrity of DNA.
Outlining prior scientific knowledge on the subject and novel information: The role of Hsp70 translocation to the nucleus
and nucleolus during heat stress has been nearly unknown. It has been proposed that this biological phenomenon is correlated
to Hsp70-chaperoning activity. Furthermore, some previous observations in yeast have revealed that Rad9 complexes—Rad9 being
the prototype DNA-damage checkpoint gene—contain Ssa1 and or Ssa2 chaperone proteins, both reconstituting the functions of
the corresponding Hsp70 in mammalian cells. Here, we propose that Hsp70 translocates to the nuclei/nucleoli during heat stress,
binds to PARP-1 and/or XRCC1, and protects HeLa cells from increased single-strand DNA breaks. 相似文献
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Jeannie Hwang Crista Adamson David Butler David R. Janero Alexandros Makriyannis Ben A. Bahr 《Life sciences》2010,86(15-16):615-623
AimsThis review posits that fatty acid amide hydrolase (FAAH) inhibition has therapeutic potential against neuropathological states including traumatic brain injury; Alzheimer's, Huntington's, and Parkinson's diseases; and stroke.Main methodsThis proposition is supported by data from numerous in vitro and in vivo experiments establishing metabolic and pharmacological contexts for the neuroprotective role of the endogenous cannabinoid (“endocannabinoid”) system and selective FAAH inhibitors.Key findingsThe systems biology of endocannabinoid signaling involves two main cannabinoid receptors, the principal endocannabinoid lipid mediators N-arachidonoylethanolamine (“anandamide”) (AEA) and 2-arachidonoyl glycerol (2-AG), related metabolites, and the proteins involved in endocannabinoid biosynthesis, biotransformation, and transit. The endocannabinoid system is capable of activating distinct signaling pathways on-demand in response to pathogenic events or stimuli, thereby enhancing cell survival and promoting tissue repair. Accumulating data suggest that endocannabinoid system modulation at discrete targets is a promising pharmacotherapeutic strategy for treating various medical conditions. In particular, neuronal injury activates cannabinoid signaling in the central nervous system as an intrinsic neuroprotective response. Indirect potentiation of this salutary response through pharmacological inhibition of FAAH, an endocannabinoid-deactivating enzyme, and consequent activation of signaling pathways downstream from cannabinoid receptors have been shown to promote neuronal maintenance and function.SignificanceThis therapeutic modality has the potential to offer site- and event-specific neuroprotection under conditions where endocannabinoids are being produced as part of a physiological protective mechanism. In contrast, direct application of cannabinoid receptor agonists to the central nervous system may activate CB receptors indiscriminately and invite unwanted psychotrophic effects. 相似文献