排序方式: 共有293条查询结果,搜索用时 468 毫秒
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Jasmina Makarević Nassim Tawanaie Eva Juengel Michael Reiter Jens Mani Igor Tsaur Georg Bartsch Roman A. Blaheta 《Journal of cellular and molecular medicine》2014,18(7):1460-1466
Molecular tumour targeting has significantly improved anti‐cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of Rapamycin (mTOR) and histone deacetylase (HDAC) inhibition has been shown not only to enhance anti‐tumour potential, but also to prevent resistance development seen under mono‐drug therapy. This investigation was designed to evaluate whether cross‐communication exists between mTOR signalling and epigenetic events regulated by HDAC. DU‐145 prostate cancer cells were treated with insulin‐like growth factor (IGF) to activate the Akt‐mTOR cascade or with the HDAC‐inhibitor valproic acid (VPA) to induce histone H3 and H4 acetylation (aH3, aH4). Subsequently, mTOR, Rictor, Raptor, p70s6k, Akt (all: total and phosphorylated), H3 and H4 (total and acetylated) were analysed by western blotting. Both techniques revealed a link between mTOR and the epigenetic machinery. IGF activated mTOR, Rictor, Raptor, p70s6k and Akt, but also enhanced aH3 and aH4. Inversely, IGFr blockade and knock‐down blocked the Akt‐mTOR axis, but simultaneously diminished aH3 and aH4. VPA treatment up‐regulated histone acetylation, but also activated mTOR‐Akt signalling. HDAC1 and 2 knock‐down revealed that the interaction with the mTOR system is initiated by histone H3 acetylation. HDAC‐mTOR communication, therefore, is apparent whereby tumour‐promoting (Akt/mTORhigh, aH3/aH4low) and tumour‐suppressing signals (Akt/mTORlow, aH3/aH4high) are activated in parallel. Combined use of an HDAC‐ and mTOR inhibitor might then diminish pro‐tumour effects triggered by the HDAC‐ (Akt/mTORhigh) or mTOR inhibitor (aH3/aH4low) alone. 相似文献
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Norris Gregory A. Burek Jasmina Moore Elizabeth A. Kirchain Randolph E. Gregory Jeremy 《The International Journal of Life Cycle Assessment》2021,26(3):528-542
The International Journal of Life Cycle Assessment - The Sustainability and Health Initiative for NetPositive Enterprise (SHINE) project is dedicated to improving the scientific basis for... 相似文献
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Suzana Tihi-Kapidi Adlija auevi Jasmina Fo
o-Solak Maja Malenica Tanja Duji Snijeana Hasanbegovi Nermina Babi Ermin Begovi 《Journal of Medical Biochemistry》2021,40(2):181
BackgroundAltered levels of many hematological parameters have been directly associated with diabetes in adults, while studies on children with type 1 diabetes mellitus are lacking. The aim of this study was to determine hematological indices in diabetic Bosnian children in comparison to healthy controls as well as to correlate their levels to blood glucose and hemoglobin A1c.Methods100 healthy and 100 children with type 1 diabetes mellitus (age 1-18) were included in this study. Complete blood count, hemoglobin A1c, and glucose were tested. Results were analysed by IBM SPSS Statistics version 23.ResultsSignificant differences (p<0.05) between healthy and diabetic children were found in relation to HbA1c, glucose, mean platelet volume, the number of white blood cells and erythrocytes, hematocrit, hemoglobin and MCH values. No gender differences or significant age differences were seen for hemoglobin, hematocrit, and MCV, while platelets, MPV, and MCH differed by age only in healthy children. When diabetic children were classified according to HbA1c levels, significant differences were seen for erythrocyte count and hematocrit value (p=0.013 and 0.019, respectively). The number of erythrocytes and white blood cells correlated significantly with HbA1c (p=0.037 and 0.027, respectively).ConclusionsLower levels of erythrocytes, hematocrit, and hemoglobin in diabetic compared to healthy children indicate possible development of anemia, while higher MCV, MCH, and MPV values indicate an alteration in erythrocyte morphology. Hematological indices could be a useful inexpensive tool in the diagnosis and follow up of type 1 diabetes in children. 相似文献
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Kouadio Ibrahime Sinan Abdurrahman Aktumsek María de la Luz Cádiz-Gurrea Francisco Javier Leyva-Jiménez Álvaro Fernández-Ochoa Antonio Segura-Carretero Jasmina Glamocilja Marina Sokovic Marija Nenadić Gokhan Zengin 《化学与生物多样性》2021,18(8):e2100299
The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application. 相似文献
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Banko MR Allen JJ Schaffer BE Wilker EW Tsou P White JL Villén J Wang B Kim SR Sakamoto K Gygi SP Cantley LC Yaffe MB Shokat KM Brunet A 《Molecular cell》2011,44(6):878-892
The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in?vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells. 相似文献
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Marković ZS Dimitrić Marković JM Milenković D Filipović N 《Journal of molecular modeling》2011,17(10):2575-2584
Density functional theory calculations were performed to evaluate the antioxidant activity of baicalein. The conformational
behaviors of both the isolated and the aqueous-solvated species (simulated with the conductor-like polarizable continuum solvation
model) were analyzed at the M052X/6-311 + G(d,p) level. The most stable tautomers of various forms of baicalein displayed
three IHBs between O4 and OH5, O5 and OH6, and O6 and OH7. The most stable tautomer of the baicalein radical was obtained
by dehydrogenating the hydroxyl at C6, while the most stable anion tautomer was obtained by deprotonating the C7 hydroxyl
in gaseous and aqueous phases. The expected antioxidant activity of baicalein was explained by its ionization potentials (IPs)
and homolytic O–H bond dissociation enthalpies (BDEs), which were obtained via the UM052X optimization level of the corresponding
radical species. Heterolytic O–H bond cleavages (proton dissociation enthalpies, PDEs) were also computed. The calculated
IP, BDE, and PDE values suggested that one-step H-atom transfer, rather than sequential proton loss–electron transfer or electron
transfer–proton transfer, would be the most favorable mechanism for explaining the antioxidant activity of baicalein in the
gas phase and in nonpolar solvents. In aqueous solution, the SPLET mechanism was more important. 相似文献
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How DNA Polymerase X Preferentially Accommodates Incoming dATP Opposite 8-Oxoguanine on the Template
Benedetta Sampoli Benítez Zachary?R. Barbati Karunesh Arora Jasmina Bogdanovic Tamar Schlick 《Biophysical journal》2013,105(11):2559-2568
The modified base 8-oxo-7,8-dihydro-2′-deoxyguanosine (oxoG) is a common DNA adduct produced by the oxidation of DNA by reactive oxygen species. Kinetic data reveal that DNA polymerase X (pol X) from the African swine fever virus incorporates adenine (dATP) opposite to oxoG with higher efficiency than the non-damaged G:C basepair. To help interpret the kinetic data, we perform molecular dynamics simulations of pol X/DNA complexes, in which the template base opposite to the incoming dNTP (dCTP, dATP, dGTP) is oxoG. Our results suggest that pol X accommodates the oxoGsyn:A mispair by sampling closed active conformations that mirror those observed in traditional Watson-Crick complexes. Moreover, for both the oxoGsyn:A and oxoG:C ternary complexes, conformational sampling of the polymerase follows previously described large subdomain movements, local residue motions, and active site reorganization. Interestingly, the oxoGsyn:A system exhibits superior active site geometry in comparison to the oxoG:C system. Simulations for the other mismatch basepair complexes reveal large protein subdomain movement for all systems, except for oxoG:G, which samples conformations close to the open state. In addition, active site geometry and basepairing of the template base with the incoming nucleotide, reveal distortions and misalignments that range from moderate (i.e., oxoG:Asyn) to extreme (i.e., oxoGanti/syn:G). These results agree with the available kinetic data for pol X and provide structural insights regarding the mechanism by which this polymerase can accommodate incoming nucleotides opposite oxoG. Our simulations also support the notion that α-helix E is involved both in DNA binding and active site stabilization. Our proposed mechanism by which pol X can preferentially accommodate dATP opposite template oxoG further underscores the role that enzyme dynamics and conformational sampling operate in polymerase fidelity and function. 相似文献