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The ADME profile of AAT was very promising with high
2020-02-10
The ADME profile of AAT-008 () was very promising, with high stability in HLM. The pre-clinical pharmacokinetic properties of AAT-008 were also assessed in rats (Sprague-Dawley, male), dogs (beagle, male), and monkeys (cynomolgus, male). The experimentally determined parameters are summarized in .
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One step in pyrimidine biosynthesis is conversion of
2020-02-10
One step in pyrimidine biosynthesis is conversion of l-dihydroorotate (DHO) to orotate (ORO), under action of the enzyme dihydroorotate dehydrogenase (DHODH, EC 1.3.99.11), which contains a flavine (FMN) as redox cofactor [1]. In this transformation, electrons resulting from DHO oxidation are transf
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DGK is not the only
2020-02-10
DGKε is not the only DGK isoform that has been associated with p53. It has been shown that DGKζ binds to p53 and modulates its activity in both the cytoplasm and the nucleus [39]. In the cytosol DGKζ promotes the degradation of p53 through the ubiquitin-proteosome system [39], also a likely mechanis
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Pulmonary fibroblasts can regulate the wound healing process
2020-02-10
Pulmonary fibroblasts can regulate the wound healing process by secreting and processing extracellular matrix (ECM), chemokines, and cytokines. However, persistent and atypical fibroblast proliferation can result in ECM accumulation and may trigger the onset or development of pulmonary fibrosis [[17
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In this study cell migration in response to
2020-02-08
In this study, cell migration in response to LTD4 exhibited a typical bell-shaped dose-response curve with optimal activity at 10 nM. However, the effect of inhaled CysLTs on airway inflammatory cells in vivo has not been widely reported to date, therefore, the role of CysLTs in the development of a
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br Materials and methods br Results br Discussion Inflammato
2020-02-08
Materials and methods Results Discussion Inflammatory signalling and in particular the arachidonic LDN-212854 australia cascade have been suggested as targets for disease modification, optimization of the therapeutic response, and even restoration of pharmacosensitivity (Potschka, 2010). R
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Bcl functions as a transcription repressor via its N
2020-02-08
Bcl6 functions as a transcription repressor via its N-terminal BTB domain and middle “second repression,” or “RD2” domain (Chang et al., 1996, Seyfert et al., 1996). A loss of function of the BCL6 BTB domain markedly impairs survival and proliferation of mature GC Procainamide HCl in a B cell intri
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To analyze EBI expression and its function in
2020-02-07
To analyze EBI2 expression and its function in T cells in vivo, we created an EGFP reporter/knockout mouse strain, termed EBI2EGFP. This mouse strain in heterozygous configuration allows for a systematic analysis of the expression of EBI2 in distinct cell types in steady-state and under inflammatory
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br Materials and methods br Results br Discussion
2020-02-06
Materials and methods Results Discussion Although no increase in DAPK activity was detected at early time points associated with neuronal apoptosis, it is possible that the spread of apoptosis through the PR957 following HI is not synchronized enough to yield a large, consistent fluctuatio
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br Use of CDK inhibitors in CLL today There
2020-02-06
Use of CDK inhibitors in CLL today There has been explosive development of novel therapeutics for CLL in the last decade and a massive transformation of practice is underway [75]. Most of this development and excitement revolves around B-cell receptor (BCR) signaling inhibitors: the Bruton tyrosi
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In this study we observed
2020-02-06
In this study, we observed alterations in mRNA levels of CRF receptors in the PFCx and Hip during the development of sensitization. In particular, in the Hip both CRF receptors showed significantly increased VX765 when the sensitization condition was established. Similarly, CRF2 receptor increase wa
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PF-00562271 In summary we hypothesize that targeting the A R
2020-02-06
In summary, we hypothesize that targeting the A1R–D1R heterotetramer with heteromer-selective drugs might improve safety and efficacy of the pharmacological therapy for RLS and other motor diseases, resulting in fewer side effects than classical drugs developed for targeting monomeric A1R or D1R.
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Among the other mediators which have been reported
2020-02-05
Among the other mediators which have been reported to play a role in erection are prostaglandins (PGs). Several studies have reported that alprostadil- synthetic PGE1- showed high efficacy in management of erectile dysfunction as it induces corpus cavernosal relaxation. Alprostadil has been first de
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These findings further extend our knowledge of how
2020-02-05
These findings further extend our knowledge of how P4 and/or E2 can mediate anxiety and fear responses. Female rats in behavioral estrous and ovx rats administered systemic P4 and/or E2 demonstrated significantly less anxiety in the open field and/or elevated plus maze, compared to diestrous rats, a
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br Funding br Disclosure of interest br Acknowledgments br I
2020-02-05
Funding Disclosure of interest Acknowledgments Introduction Pulmonary fibrosis (PF) is a chronic disease characterized by extensive deposits of the extracellular matrix (ECM) that can impair the architecture and function of the lungs (Cavazza et al., 2010). Imbalance between the prolifer
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