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Prostaglandin E PGE is involved
2020-03-11
Prostaglandin E2 (PGE2) is involved in several biological processes such as renal function, inflammation, angiogenesis, and tumor growth. The various biological effects of PGE2 are mediated by the so-called E-type prostanoid receptors (EP1 to EP4). Among these, the EP4 receptor has been well studied
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We should also note that oxygen pressure
2020-03-11
We should also note that oxygen pressure of Krebs solution bubbled with 95% O2+5% CO2 as we used in our study is reported to around 400 mmHg in several studies [48], [49], which is higher than normal arterial O2 pressure (80–100 mmHg). Although superoxide generation at elevated O2 tensions are noted
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br Introduction Our understanding of how ligands interact wi
2020-03-11
Introduction Our understanding of how ligands interact with G protein coupled receptors is evolving, particularly the recognition that some have the ability to preferentially activate a subset of intracellular signalling cascades – so called pathway biased ligands [1]. Additionally, it is now ac
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Metal ions are known not to be necessary
2020-03-11
Metal ions are known not to be necessary for catalytic activity of serine proteinases. Nevertheless, Co2+ and Ca2+ ions were found to stabilize glutamyl endopeptidase molecule [1], [7], [19]. In our previous study, we have described significant stimulating effect of Ca2+, Mg2+, and Co2+ on biosynthe
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A factor that complicates the use of human liver cells
2020-03-10
A factor that complicates the use of human liver Ezatiostat hydrochloride is one of variability, which arises in part because many of the human liver samples available for research show various stages of a variety of disease states (steatosis (fatty liver), cirrhosis, carcinogenesis in adjacent tis
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Several highly potent CysLT receptor antagonists with large
2020-03-10
Several highly potent CysLT1 receptor antagonists with large structural PFI-2 synthesis have been developed. Beyond antagonists with structures analogous to cysteinyl leukotrienes, other subclasses comprise: (a) hydroxyacetophenones, (b) indoles and indazoles, (c) quinolines, benzothiazoles, and th
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It would be very useful if unphosphorylated CK
2020-03-10
It would be very useful if unphosphorylated CK1s could be prepared using an E. coli expression system without the troublesome in vitro phosphatase treatment. So far, it has been shown that coexpressed λPPase, a Mn2+-dependent protein phosphatase that can dephosphorylate phospho-Ser/Thr/Tyr [20,21],
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MTX and MTXPGs block the activity of the key enzyme
2020-03-10
MTX and MTXPGs block the activity of the key enzyme DHFR (Fig. 1), which converts folates to their active forms – dihydrofolate (DHF) and tetrahydrofolate (THF). MTXPGs also potently inhibit thymidylate synthase (TS). Furthermore, during dTMP synthesis, TS utilizes the cofactor 5,10-methylene THF, w
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cyclin dependent kinases br Fragment based drug discovery FB
2020-03-10
Fragment-based drug discovery (FBDD) is a powerful method to discover drug leads and has been widely adopted in both academia and industry. FBDD can be used to explore chemical cyclin dependent kinases space with libraries which are smaller in size, producing drug leads with high ligand-binding e
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On the other hand p responds to environmental
2020-03-10
On the other hand, p38 responds to environmental stress, including ultraviolet light, heat, osmotic shock, and inflammatory cytokines (Pearson et al., 2001, Kumar et al., 2003), and is activated in astrocytes after ischemia-like injury (Yung and Tolkovsky, 2003, Niu et al., 2009). Moreover, p38 acti
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Introduction Cysteinyl leukotrienes CysLTs LTC
2020-03-10
Introduction Cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4, are 5-lipoxygenase pathway metabolites of arachidonic AM095 and deeply involved in bronchial asthma via activation of CysLT1 receptors [1], [2]. Specific CysLT1 receptor antagonists, including pranlukast [3], [4] and montelukast [5
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Beside the previously reported Topo I inhibition time
2020-03-10
Beside the previously reported Topo I inhibition, time and concentration dependent CRM1 inhibitory properties of klavuzon derivatives have been shown as a second mechanism of action in this work. Especially, compounds 3 and 20 are the most effective derivatives and they completely inhibit CRM1 activ
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In the current study although EP agonist was
2020-03-10
In the current study, although EP4 agonist was the most effective in relaxing corpus cavernosum, it did not affect the neuronally-mediated relaxation. On the other hand, both alprostadil and iloprost, which were less effective as direct relaxants, potentiated EFS-induced relaxation of rat corpus cav
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As shown in Figs a
2020-03-10
As shown in Figs. 3(a) and (b), with the SO effect, the absolute values of the VDEs change by at most 0.19eV. Table 1 also shows that the observed peak splitting energies in the Sm-Ho complexes were reproduced even without the SO effect. Considering its significant importance in the electronic struc
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br Loss of Chk sensitizes cells to
2020-03-09
Loss of Chk 1 sensitizes in the same way to hypoxia/reoxygenation In contrast to Chk 2, studies have identified Chk 1 as being phosphorylated in an ATR-dependent manner at residue serine 345 during hypoxia [18]. More recently, siRNA mediated inhibition of Chk 1 signaling was found to sensitize ce
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