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One limitation of our study was
2022-08-26

One limitation of our study was that all control dogs had histologic evidence of mild GI inflammation according to established WSAVA guidelines (Washabau et al., 2010), despite being apparently healthy purpose-bred research dogs housed in a controlled environment with no history of vomiting, diarrhe
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Under normal physiological conditions the body has sufficien
2022-08-26

Under normal physiological conditions, the body has sufficient oxygen supply, so glucose can produce large amounts of ATP by aerobic oxidation and oxidative phosphorylation in cells. After SCI, hypoxia ischemia can occur in local tissue, leading to decreasing of intracellular oxygen partial pressure
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In diseased blood vessels increased production of reactive
2022-08-26

In diseased blood vessels, increased production of reactive oxygen species (ROS), such as peroxynitrite, superoxide, and hydrogen peroxide, have been found [[53], [54], [55]]. Peroxynitrite was suggested to alter the redox state of sGC [53] while hydrogen peroxide interfered with the action of NO bu
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1602 Several compounds have been described in
2022-08-26

Several compounds have been described in the literature as inhibitors of the sGC. Among them, methylene blue and LY83583 () are not direct sGC inhibitors, but rather block cGMP formation by generating superoxide anion radicals that deactivate NO. Despite their extensive use in plethora of research s
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br Introduction The discovery that the nitric oxide NO
2022-08-26

Introduction The discovery that the nitric oxide (NO), soluble guanylate cyclase (sGC), and cyclic guanosine monophosphate (cGMP) pathway mediates erection has led to the use of phosphodiesterase type 5 (PDE-5) inhibitors as the gold standard for treating erectile dysfunction (ED) through the inh
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Because of its excellent GPR
2022-08-26

Because of its excellent GPR119 potency, good hERG selectivity and favorable rat t, casr was scaled-up and further profiled. The synthetic protocols described in , were both suitable for a multi-gram scale synthesis of compound . An off-target screen was performed against an extensive panel of 16
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Disrupting the dialog between microbiota and the host
2022-08-26

Disrupting the dialog between microbiota and the host, especially at the level of mucosal immunology, is expected to have profound effects on disease development. By using the AOM+DSS model of colitis-associated CRC, Singh et al. (2014) showed that development of inflammation and CRC are exacerbated
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With this goal in mind we proceeded to
2022-08-26

With this goal in mind, we proceeded to explore the C5-heteroaryl class of pyrazole-acids. Initial efforts, focused on a thiophene replacement, demonstrated little improvement. The 2-thiophene derivative (0.25μM and 0.24μM), a surrogate to the phenyl moiety, demonstrated only a modest boost in acti
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d-glucose Based on work from our labs with mGlu
2022-08-26

Based on work from our labs with mGlu NAMs, and the ability of [3.3.0] systems, such as the octahydropyrrolo[3,4-]pyrrole, to effectively mimic piperazines, we focused our attention on the potential bioisoteric replacement of the [3.1.0] system of and , as well as the piperidine of , with a [3.3.0]
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The aim of our study was to investigate
2022-08-26

The aim of our study was to investigate the polymorphisms of RAGE and glyoxalase I gene and sRAGE serum levels in patients with pathological pregnancy trying to describe the genetic background of pathological pregnancy or to find a new biochemical marker (sRAGE) of these pathological states in pregn
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77 br Brief overview of the glutamate system and
2022-08-26

Brief overview of the glutamate system and rationale for targeting the glycine site of NMDARs In the central nervous system (CNS), glutamate is the major excitatory neurotransmitter and works in concert with gamma-aminobutyric 77 (GABA), the primary inhibitory neurotransmitter. Together, GABA and
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In conclusion we have designed and characterized a novel ser
2022-08-26

In conclusion, we have designed and characterized a novel series of EAAT-blockers, exemplified by (-[4-(2-bromo-4,5-difluorophenoxy)phenyl]--asparagine)—a potent, selective, competitive non-substrate inhibitor of EAAT-2. As one of the most potent and selective EAAT-2 inhibitors identified to date,
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Genetic disruption or pharmacologic inhibition
2022-08-25

Genetic disruption or pharmacologic inhibition of the hepatic glucagon pathway has invariably been shown to increase pancreatic α cell mass. This has been observed in glucagon receptor (GCGR) knockout (Gcgr−/−) mice (Gelling et al., 2003), glucagon knockout mice (Hayashi et al., 2009), prohormone co
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br Conflicts of interests br Acknowledgements We
2022-08-25

Conflicts of interests Acknowledgements We thank Drs. T. Tomita and T. Iwatsubo (Tokyo University, Tokyo, Japan) for anti-presenilin 1-CTF antiserum, Dr. A. Takashima (Gakushuin University, Tokyo, Japan) for anti-Pen-2 antiserum and the laboratory members for helpful comments and discussion. M
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The synthesis of compounds and
2022-08-25

The synthesis of compounds and were achieved according to standard procedures. As shown in , The compound 4-methyl-1-(4-sulfobutyl)quinolonium () was prepared by alkylation reaction. Compounds and were synthesized by substitution reactions between 4-fluorobenzaldehyde and , , '-trimethylethanediamin
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