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142.
It is well established that Foxo3a is a fundamental module of signal transduction pathways regulating erythropoiesis; however, precise mechanism which regulates its physiological function still remains unclear. Here, our results revealed that the nuclear localization and stability of Foxo3a were modulated by the physical interaction of PKC and p38 signaling elements and that direct interactions led to phosphorylation of threonine residue(s) in Foxo3a. In addition, our findings revealed that the sequential activity of Foxo3a by guanosine 5′-triphosphate can impede cellular proliferation and suppress p73 expression as oncoprotein in K562 cells; thus identifying Foxo3a as a tumor suppressor in these p53 null cells. However, down-regulation of Foxo3a-dependent p73 expression causes cell differentiation along the erythroid lineage. Collectively, our findings suggest that restoration of Foxo3a function by pharmacological agents under the influence of specific activated protein kinases might constitute a potential therapeutic strategy for combating the CML disease. 相似文献
143.
Joulia Alizadeh-Rahrovi Alireza Shayesteh Azadeh Ebrahim-Habibi 《Journal of biological physics》2015,41(4):349-366
Glycoproteins are formed as the result of enzymatic glycosylation or chemical glycation in the body, and produced in vitro in industrial processes. The covalently attached carbohydrate molecule(s) confer new properties to the protein, including modified stability. In the present study, the structural stability of a glycoprotein form of myoglobin, bearing a glucose unit in the N-terminus, has been compared with its native form by the use of molecular dynamics simulation. Both structures were subjected to temperatures of 300 and 500 K in an aqueous environment for 10 ns. Changes in secondary structures and RMSD were then assessed. An overall higher stability was detected for glycomyoglobin, for which the most stable segments/residues were highlighted and compared with the native form. The simple addition of a covalently bound glucose is suggested to exert its stabilizing effect via increased contacts with surrounding water molecules, as well as a different pattern of interactions with neighbor residues.
Electronic supplementary material
The online version of this article (doi:10.1007/s10867-015-9383-2) contains supplementary material, which is available to authorized users. 相似文献144.
Improved production of erythromycin by Saccharopolyspora erythraea by various plant oils 总被引:1,自引:0,他引:1
Various plant oils (50 g l–1) increased the production of erythromycin by Saccharopolyspora erythraea. Maximum titer of erythromycin in media containing black cherry kernel, walnut, rapeseed, olive and cottonseed oils and control medium were 3.5, 2.8, 2.6, 2.1, 1.9, 0.7 g l–1, respectively. Erythromycin production media containing rapeseed or cottonseed oil was growth-dependent but not in other media used. 相似文献
145.
Hadi Esmaily Azadeh Hosseini-Tabatabaei Reza Rahimian Reza Khorasani Maryam Baeeri Ahmadreza Barazesh-Morgani Nargues Yasa Yassaman Khademi Mohammad Abdollahi 《Central European Journal of Biology》2009,4(2):204-213
Inflammatory bowel disease (IBD) is a multifactorial disease with an unknown etiology characterized by oxidative stress, leucocyte
infiltration and a rise in inflammatory cytokines. In this study, we have investigated the effects of silymarin, a mixture
of several flavonolignans with established antioxidant and anti-inflammatory properties, on trinitrobenzene sulphonic acid
(TNBS)-induced colitis in rats. Experimental colitis was induced in male Wistar-albino rats by delivering TNBS to the distal
colon. All the medicines were administered by gavage for seven days. Thirty-six male rats were divided into six groups containing
six rats in each one. Control rats received only TNBS. In the treated groups, animals were given different doses of silymarin
(40, 80, and 160 mg/kg). Dexamethasone (1 mg/kg) was used as the positive treatment. Colonic status was investigated seven
days post induction of colitis through macroscopic, histological, and biochemical analyses. Amelioration of the morphological
signs including macroscopic damage, necrotic area, and histology were seen subsequent to treating animals with silymarin.
These observations were accompanied by a significant reduction in the degree of both neutrophil infiltration, indicated by
decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malodialdehyde content in inflamed
colon as well as a decrease in levels of inflammatory cytokines (TNF-α and IL-1β). The results of the present study reveal
that the beneficial effect of silymarin in bowel cells is mediated through its anti-oxidant and anti-inflammatory potentials. 相似文献
146.
Martina Klevstig Bani Mukhopadhyay Mattias Bergentall Resat Cinar Marcus Ståhlman Natasha Sikanic Joshua K Park Sumit Deshmukh Azadeh M Harzandi Tim Kuijpers Morten Grøtli Simon J Elsässer Brian D Piening Michael Snyder Ulf Smith Jens Nielsen Fredrik Bäckhed George Kunos Mathias Uhlen Jan Boren Adil Mardinoglu 《Molecular systems biology》2017,13(8)
We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co‐expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver‐specific genes co‐expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver‐specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver‐specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin‐like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development. 相似文献
147.
Ouafa Najyb Sonia Do Carmo Azadeh Alikashani Eric Rassart 《Molecular neurobiology》2017,54(6):3948-3963
Excitotoxicity due to the excessive activation of glutamatergic receptors leads to neuronal dysfunction and death. Excitotoxicity has been implicated in the pathogenesis of a myriad of neurodegenerative diseases with distinct etiologies such as Alzheimer’s and Parkinson’s. Numerous studies link apolipoprotein D (apoD), a secreted glycoprotein highly expressed in the central nervous system (CNS), to maintain and protect neurons in various mouse models of acute stress and neurodegeneration. Here, we used a mouse model overexpressing human apoD in neurons (H-apoD Tg) to test the neuroprotective effects of apoD in the kainic acid (KA)-lesioned hippocampus. Our results show that apoD overexpression in H-apoD Tg mice induces an increased resistance to KA-induced seizures, significantly attenuates inflammatory responses and confers protection against KA-induced cell apoptosis in the hippocampus. The apoD-mediated protection against KA-induced toxicity is imputable in part to increased plasma membrane Ca2+ ATPase type 2 expression (1.7-fold), decreased N-methyl-d-aspartate receptor (NMDAR) subunit NR2B levels (30 %) and lipid metabolism alterations. Indeed, we demonstrate that apoD can attenuate intracellular cholesterol content in primary hippocampal neurons and in brain of H-apoD Tg mice. In addition, apoD can be internalised by neurons and this internalisation is accentuated in ageing and injury conditions. Our results provide additional mechanistic information on the apoD-mediated neuroprotection in neurodegenerative conditions. 相似文献
148.
Fatemeh Ebrahimi Hadi Esmaily Maryam Baeeri Azadeh Mohammadirad Saeed Fallah Mohammad Abdollahi 《Central European Journal of Biology》2008,3(2):135-142
Inflammatory bowel disease (IBD) is a chronic recurrent disease of the digestive tract with an unknown etiology. The aim of
this study was to examine the possible protective effects of N-acetylcysteine (NAC) in the mouse model of IBD by measuring
specific biomarkers in the colon cells. Colitis was induced by administration of dextran sodium sulfate (DSS) in drinking
water (3%) for 7 days. Three doses of NAC (106, 160, and 240 mg/kg) were given after induction of colitis (4 days post DSS)
for 4 days by gavage. Lipid peroxides (LP), total antioxidant power (TAP), total thiol molecules (TTM), tumor necrosis factor-α
(TNF-α), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT) were measured in the colon homogenate of the treated
animals. NAC (160 and 240 mg/kg) significantly decreased LP, TNF-α, NO and increased TTM, SOD, and CAT. The TAP was also increased
by NAC (240 mg/kg). It is concluded that moderate to high doses of NAC improves cellular biomarkers of IBD in mice. Further
studies should be trialled in humans suffering from two common inflammatory bowel disease called ulcerative colitis and Crohn’s
disease. 相似文献
149.
Background
High throughput gene expression data from spotted cDNA microarrays are collected by scanning the signal intensities of the corresponding spots by dedicated fluorescence scanners. The major scanner settings for increasing the spot intensities are the laser power and the voltage of the photomultiplier tube (PMT). It is required that the expression ratios are independent of these settings. We have investigated the relationships between PMT voltage, spot intensities, and expression ratios for different scanners, in order to define an optimal scanning procedure. 相似文献150.
In solving the gene prioritization problem, ranking candidate genes from most to least promising is attempted before further experimental validation. Integrating the results of various data sources and methods tends to result in a better performance when solving the gene prioritization problem. Therefore, a wide range of datasets and algorithms was investigated; these included topological features of protein networks, physicochemical characteristics and blast similarity scores of protein sequences, gene ontology, biological pathways, and tissue-based data sources. The novelty of this study lies in how the best-performing methods and reliable multi-genomic data sources were applied in an efficient two-step approach. In the first step, various multi-genomic data sources and algorithms were evaluated and seven best-performing rankers were then applied to prioritize candidate genes in different ways. In the second step, global prioritization was obtained by aggregating several scoring schemes.The results showed that protein networks, functional linkage networks, gene ontology, and biological pathway data sources have a significant impact on the quality of the gene prioritization approach. The findings also demonstrated a direct relationship between the degree of genes and the ranking quality of the evaluated tools. This approach outperformed previously published algorithms (e.g., DIR, GPEC, GeneDistiller, and Endeavour) in all evaluation metrices and led to the development of GPS software. Its user-friendly interface and accuracy makes GPS a powerful tool for the identification of human disease genes. GPS is available at http://gpsranker.com and http://LBB.ut.ac.ir. 相似文献