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We have previously disclosed the discovery of a
2020-09-27
We have previously disclosed the discovery of a 7-azaindole-3-acetic Meropenem CRTh2 antagonist chemotype 1 from HTS and its subsequent optimization to give 2 as a potent and orally bioavailable inhibitor of eosinophil shape change (SC) in human whole blood. Subsequent to disclosure of that work, ot
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Multiple lines of evidence now indicate that mitochondrial
2020-09-27
Multiple lines of evidence now indicate that mitochondrial decay is a fundamental factor that leads to alterations in energy metabolism in the aged heart (Hagen et al., 2002, Judge and Leeuwenburgh, 2007, Lesnefsky et al., 2001c). Nevertheless, the exact biochemical events that cause such an alterat
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VHb expression in recombinant E coli expressing P
2020-09-27
VHb expression in recombinant E. coli expressing P4H improved Hyp production, presumably by enhancing oxygen transfer. VHb expression contributed to improving growth and extending the period of exponential growth in both shaker flask culture and bioreactor fermentation. A similar phenomenon was also
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br Funding This work was
2020-09-25
Funding This work was supported by the National Natural Science Foundation of China (grant number 81671411); Beijing Natural Science Foundation (grant number 7162062); Beijing Nova Program Interdisciplinary Cooperation Projects (grant number Z161100004916045); Beijing Municipality Health Technolo
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br Oxidoreductase like MEM for
2020-09-25
Oxidoreductase-like MEM for prodrug activation Future outlook Although MEM-mediated prodrug activation has been performed by different MEMs and prodrugs, and their effectiveness have been proved in vivo, only a few types of MEMs or prodrugs have been explored in prodrug activation until now [2
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br Results br Discussion br Materials and Methods br Acknowl
2020-09-25
Results Discussion Materials and Methods Acknowledgment This work was funded by the Collaborative Research Centre (SFB) 807 of the German Research Foundation (DFG) and supported by the state of Hessen (Center for Biomolecular Magnetic Resonance) and the German Research Foundation (DO545/
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The redox sensitive transcription factor NF
2020-09-25
The redox sensitive transcription factor NF-κB is reported to play a crucial role in the COPD pathogenesis via up regulating the expression of several cytokines, chemokines, growth factors, and adhesion molecules [71]. Incidentally, we and others have shown that PARP-1 modulates the NF-κB activation
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br Introduction Esophageal squamous cell carcinoma ESCC is o
2020-09-25
Introduction Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in East Asia and is a leading cause of cancer-related death worldwide.1, 2 Surgery is widely used for treatment in localized disease, where it can provide definitive management and potential cure. Tre
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br Ubiquitylation of the TGF
2020-09-25
Ubiquitylation of the TGFβ/BMP pathway components Ubiquitylation is a reversible post-translational modification that is essential in many cellular regulatory mechanisms [20], [21]. During the ubiquitylation cascade, ubiquitin is attached to target proteins through the concerted actions of an E1-
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Introduction Rotavirus RV a member of Reoviridae
2020-09-25
Introduction Rotavirus (RV), a member of Reoviridae family, is a non-enveloped virus which has a double-stranded RNA genome of 11 segments surrounded by three concentric protein layers. It has been reported to cause estimated 25% of moderate-to-severe illnesses (Kotloff et al., 2013) and 30% of tot
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In this context we initiated a program to develop new
2020-09-24
In this context, we initiated a program to develop new antiviral chemotypes towards a host factor implicated in 5-Ethynyl-2\'-deoxyuridine replication: the host (human) dihydrofolate reductase (DHFR) [21]. We recently identified this enzyme as the molecular target of 1-aryl-4,6-diamino-1,2-dihydrot
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The changes in the chemokine receptors CCR
2020-09-24
The changes in the chemokine receptors CCR-5 and CXCR-4 in women and men with PTSD are completely different. In the group of women with PTSD alone the level of this benfotiamine increased six times, whereas, in women with APD and PTSD, the level of the receptor CCR-5 was eight times higher than in t
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Furthermore haplotypes formed by rs rs rs
2020-09-24
Furthermore, haplotypes formed by rs6269, rs4633, rs4818, and rs4680 of the COMT gene constitute a central COMT locus haploblock that is associated with the enzymatic activity of COMT [8]. The SNPs rs6269 and rs4818, which are located in the central COMT locus haploblock, have been observed to be as
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So what can we glean from this illuminative foray
2020-09-24
So what can we glean from this illuminative foray into how Chk1 and MK2 participate in checkpoint control? First and foremost, this work reveals that GDC-0623 deficient in the tumor suppressor p53 contain two spatially distinct G2/M phase checkpoint control kinase networks. This provides compelling
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Berner et al used a meta analysis to
2020-09-24
Berner et al used a meta-analysis to show that sildenafil resulted in an effect of 9.65-point improvement. Tadalafil could be pooled into an effect of 8.52-point improvement, and vardenafil showed an effect of 7.50-point improvement. In our present studies, 200 mg udenafil resulted in an effect of 8
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