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The fine interplay among post translational modifications an
2022-04-19
The fine interplay among post-translational modifications and intersection with other pathways, such as PI3K–AKT, has a crucial role in the regulation of GLI activity and in the generation of their repressor forms 40, 41, 42. In addition to β-TrCP, for example, other E3 ligases belonging to the real
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The most classic case of acquired and relapsing
2022-04-19
The most classic case of acquired and relapsing epilepsy is temporal lobe epilepsy (TLE), which originates from the hippocampal formation, a structure situated in the mesial temporal lobe (Majores et al., 2007). Our experiment used the prominent pilocarpine-induced TLE model. Systemic administration
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PBI is an agonist of
2022-04-19
PBI-4050 is an agonist of GPR40 and acts as an antagonist or inverse agonist of GPR84. It cannot be excluded that other targets besides GPR40 and GPR84 could be implicated in the mechanism of action of PBI-4050 and could be explored in future studies. However, the present study, and in particular th
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MMV s distinct mode of inhibition addresses key impediments
2022-04-19
MMV019313's distinct mode of inhibition addresses key impediments in the development of PfFPPS/GGPPS inhibitors as antimalarial drugs. First, it is the first non-bisphosphonate inhibitor of Plasmodium FPPS/GGPPS with drug-like physicochemical properties satisfying the “Rule of 5” (Van Voorhis et al.
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There are several basic science studies that aim
2022-04-19
There are several basic science studies that aim to investigate potential mechanisms behind the reduced incidence of MI in factor Xa inhibitor treated patients. Perzborn et al. reported that in-vitro addition of rivaroxaban reduced tissue-factor induced platelet aggregation (Perzborn, Heitmeier, & L
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Potential platelet related mechanisms that might explain an
2022-04-19
Potential platelet-related mechanisms that might explain an augmented risk of MI in dabigatran treated patients have been investigated: Enhanced platelet reactivity is known to be associated with the risk of MI (Mangiacapra et al., 2018) and catalytically active thrombin is a potent stimulus to indu
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Otamixaban H O induced astrocyte ATP release through lysosom
2022-04-19
H2O2 induced astrocyte ATP release through lysosome exocytosis. The LDH assay and electric microscope results indicated that the increase of extracellular ATP concentration was not due to the cell rupture, but the alternations in cell activities. In addition, when lysosome exocytosis was blocked by
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In vitro studies suggest that the increase in
2022-04-19
In vitro studies suggest that the increase in Hx activity seen in normal pregnancy may contribute to the down-regulation of the vascular expression of Angiotensin II receptor 1 thereby promoting a relaxed and dilated maternal vascular bed [25]. It has further been suggested that the decreased Hx act
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In order for cytokines to exert any effect on
2022-04-18
In order for cytokines to exert any effect on the NSC population, they must first bind to specific receptors on the cell surface. Numerous pro- and anti-inflammatory cytokines are able to exert effects on the NSC population, including IL-1β through IL-1R1 and IL-1R2, TNFα through TNFR1 and TNFR2, IL
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The compounds described in this paper were prepared using a
2022-04-18
The compounds described in this paper were prepared using a modular approach that allowed diversification of R or R at the final step (). Route A involved amide coupling of -butyl 4-(methylamino)piperidine-1-carboxylate with phenyl acetic acids (step a) using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-m
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SGCs tightly ensheath the soma of DRG neurons Costa and
2022-04-18
SGCs tightly ensheath the soma of DRG neurons (Costa and Moreira, 2015, Hanani, 2005, Takeda et al., 2009). Intimate associations between SGCs and neurons facilitate bidirectional regulation of SGC function and neuronal excitability. After nerve injury, neuronal hyperexcitability can result in SGC a
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The HRTOF MS of showed a quasi molecular ion
2022-04-18
The HRTOF-MS of showed a quasi-molecular ion peak at / 525.3044 [M+Na], corresponding to a quasi-molecular formula of CHNONa (Calcd for CHNONa: 525.3053). IR absorptions at 1680 and 1522cm suggested the presence of amide functions. Based on an analysis of 1D and 2D NMR spectra, the presence of one p
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The glycine receptor is an ionotropic
2022-04-18
The glycine receptor is an ionotropic neurotransmitter receptor coupled to a chloride ion channel. Glycine receptors are typically described as inhibitory and distributed in the spinal cord and brainstem, though mRNA transcription labelling studies in rats show expression in the hippocampus, cingula
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CEP-32496 HSOR belonging to the aldoketo reductase superfami
2022-04-18
3α-HSOR, belonging to the aldoketo reductase superfamily, is a rate-limiting enzyme for the synthesis of 3α-reduced steroids, such as allopregnanolone and tetrahydrodeoxycorticosterone. 3α-HSOR was extensively expressed in the spinal dorsal horn and was upregulated following peripheral nerve injury,
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Next we focused on B part the
2022-04-18
Next, we focused on B-part, the phthalazine ring. While both nitrogen atoms of the phthalazine ring were found to be important (data not shown), replacing the benzene ring of the phthalazine part was attempted, and shows the results of the substituted pyridazine rings with bearing 2-methoxy benzene
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