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The excellent potencies selectivities and improved PK associ
2024-09-11
The excellent potencies, selectivities and improved PK associated with the piperazine class triggered more extensive off-target screenings of the highlighted compounds. A screen of more than 100 enzymes, receptors, and ion channels resulted in activity at the norepinephrine transporter (NET). This
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In the vasculature it is known that A A and
2024-09-11
In the vasculature, it is known that A2A and A2B adenosine receptors are stimulatory for adenylyl-cyclase, leading to cyclic-AMP (cAMP) production and vasodilation, while the A1 and A3 adenosine receptors are linked to the inhibitory Gi, suppressing adenylyl-cyclase and favoring contraction. However
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br ATX LPA pathway in animal models of rheumatoid
2024-09-10
ATX–LPA pathway in animal models of rheumatoid arthritis Several animal models have been used to characterize the mechanisms involved in the pathogenesis of arthritis and to test new therapeutic strategies. The collagen-induced arthritis (CIA) model (Courtenay et al., 1980, Luross and Williams, 2
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br Involvement of LPA receptors in cancer LPA s effects
2024-09-10
Involvement of LPA receptors in cancer LPA׳s effects are mediated by at least six different G protein-coupled receptors (LPA1–6). Human gastric and ovarian cancers overexpress the mRNA encoding LPA1 and LPA2 compared to healthy tissues [6], [11], [12]. Papillary and follicular thyroid cancers ex
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Phospholipases cleave membrane phospholipids from inflammato
2024-09-10
Phospholipases cleave membrane phospholipids from inflammatory cells, activated platelets, erythrocytes, adipocytes and cancer 76 2 (Aoki et al., 2008, Neidlinger et al., 2006). Several reports have analysed the role of LPA and its receptors in the pathogenesis of RA. Zhao et al. reported that LPA
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In HepG cells compound showed inhibition of total lipid synt
2024-09-10
In HepG2 cells, SLx-2119 receptor showed inhibition of total lipid syntheses with an IC of 8μM. A cell based Alamar Blue cytotoxicity assay was used in parallel to differentiate the effect on the inhibition of lipid synthesis versus potential cytotoxicity. Under identical incubation conditions, comp
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58 4 Oocytes from the African clawed frog Xenopus
2024-09-10
Oocytes from the African clawed frog Xenopus laevis have been widely used as an expression system to study the modulation of NMDA receptors by metabotropic receptors, such as metabotropic glutamate receptors [12], μ opioid receptors [13], insulin receptors [14] and serotonin receptors [15]. No data
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In the nineties we knew that baclofen
2024-09-10
In the nineties we knew that (-)baclofen was the stereo-selective ligand for the GABAB receptor which had been recognised by Norman Bowery as a receptor for GABA, which was different from the GABAA receptor (Hill and Bowery, 1981). GABAB receptor antagonists were also synthesised and made available
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Several alterations have been or can
2024-09-10
Several alterations have been or can be associated to the decreased tolerance of steatotic liver to I/R injury. Previous studies demonstrated that upregulation of the mitochondrial uncoupling protein-2 (UP2) is strictly related to the increase of I/R injury in steatotic liver [4]. UPR induction is c
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In this study we showed that TRIM
2024-09-10
In this study, we showed that TRIM48 promotes ASK1 activation through ubiquitination-dependent degradation of a negative regulator of ASK1 activation, protein arginine methyltransferase 1 (PRMT1). Knocking down TRIM48 suppressed oxidative-stress-induced cell death mediated by ASK1, and the additiona
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The previous reports studied only the apoptosis process in
2024-09-10
The previous reports studied only the apoptosis process in a single cell. In our case we generalized these models inspired by the results of Albeck et al. (2008) and Raychaudhuri et al. (2008), to study the apoptosis cell death after photodynamic therapy in those areas of the tumor that are not expo
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Expression subcellular localization transcriptional activity
2024-09-10
Expression, subcellular localization, transcriptional activity and protein stability of Foxo are regulated by proteins such as STAT3, PKB, JNK and AMPK (Sun et al., 2017; Zhang et al., 2011). STAT3 is a member of the signal transducer and activator of transcription (STAT) protein family that plays c
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Enhancers are short regions of DNA
2024-09-10
Enhancers are short regions of DNA that are bound by DNA-binding proteins (TFs) to increase the likelihood of a particular gene to be expressed. Importantly, enhancers can be identified, and classified, by their patterns of chromatin accessibility and of enrichment in certain histone modifications.
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Furthermore a recently published network meta
2024-09-10
Furthermore, a recently published network meta-analysis including 30 trials in patients with hypertension and diabetes demonstrated that ARBs have efficacy similar to that of ACEIs for all-cause and cardiovascular mortality (HR 0.95, 95% CI 0.73 to 1.30 and HR 1.23, 95% CI 0.64 to 2.78, respectively
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Immunohistochemistry in tissue samples showed the expression
2024-09-10
Immunohistochemistry in tissue samples showed the expression of several nuclear receptor co-activators, including NCOA1, NCOA2, NCOA3, CREBBP, and EP300, in 85–100% of Solamargine australia tumors even some of which lacked AR expression (Boorjian et al., 2009). Knockdown of each co-activator also re
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