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Considering these reports and with
2021-09-01
Considering these reports, and with the aim of further investigating the mechanism by which the cAMP-Epac/PKA pathway activates eNOS, we have performed imaging experiments evaluating the effect of drugs that increase cAMP or modify its signalling pathways (PKA or Epac activators and inhibitors) on b
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Although MMP might be a downstream target
2021-09-01
Although MMP-9 might be a downstream target of Src kinase signaling (Liu and Sharp, 2011), a direct connection has not been established. We showed for the first time that, in the collagenase-induced ICH model, Src kinase signaling regulates MMP-9 activity and mediates EP1R toxicity. Consistent with
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The prospects of the use of this novel approach for
2021-09-01
The prospects of the use of this novel approach for the selective local thermo-activation of enzymes include biomedical and biotechnological applications. As NPs could be engineered to gain access to Benztropine mesylate through the endosomal compartment [47] or through non-endocytotic pathways [48
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Downregulation of tumor suppressors is a
2021-09-01
Downregulation of tumor suppressors is a major factor that leads to tumorigenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a common tumor suppressor, the blz of which is often downregulated or even absent in the majority of human cancers, functions as a phosphatase to dephos
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A range of therapies exists for the
2021-08-31
A range of therapies exists for the treatment of inflammation-driven diseases, which can be summarized as non-steroidal anti-inflammatory drugs (NSAIDs), corticoids and steroidal-related drugs (Ward et al., 2008). Despite of these notable successes, there are still major unmet medical needs in the t
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br Funding This work was
2021-08-31
Funding This work was supported by grants to A.S. from the Swedish Cancer Foundation, Sweden (Grant number: CAN, 2015/637), the Swedish Medical Council, Sweden (Grant number: 2017- 01274), the Foundations at Skåne University Hospital, Sweden and to KB, SRS, NC, BCS, and SS from the Royal Physiogr
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CDK S phosphorylation status influences the differential cel
2021-08-31
CDK5-S47 phosphorylation status influences the differential cellular proliferation versus migration response: Previous work from our laboratory has shown CDK5 to be a critical determinant of the cellular proliferation-migration dichotomy whereby CDK5 activation downstream of stimulated epidermal gro
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Next we evaluated the therapeutic potential of compound
2021-08-31
Next, we evaluated the therapeutic potential of compound () using the mouse model of collagen-induced arthritis (CIA model), which is the pathological model for RA. Consequently, oral once-daily dosing of 3 mg/kg reduced the overall progression of the clinical score, including inflammation and bone
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Among the various neurotransmitter systems pointed
2021-08-31
Among the various neurotransmitter systems pointed out to play a role in the mediation of defensive and antinociceptive responses elicited by environmentally aversive stimuli, the neuropeptide corticotropin-releasing factor or hormone (CRF or CRH) has attracted the interest of many researchers inves
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AR-12 P H is a nonheme
2021-08-31
P4H is a nonheme iron(II) dioxygenase that uses O2 and α-ketoglutarate as co-substrates (Fig. 1A). The three-dimensional structure of mammalian P4H is unknown. We reasoned that an electrophilic analog of α-ketoglutarate could serve as an irreversible inhibitor of the enzyme and, hence, a useful prob
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Introduction Prolyl hydroxylation is a widely
2021-08-31
Introduction Prolyl hydroxylation is a widely observed post translational modification in collagen, an abundant animal protein. The high content (~13% per chain of the triple helical structure) of 4-hydroxyproline (Hyp,O) in collagen, togather with the natural abundance of collagen has led to the e
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During ischemia the impact of CK on mitochondria varies
2021-08-31
During ischemia, the impact of CK2 on mitochondria varies in different organs/tissues. For example, CK2α upregulation during ischemia leads to disrupted mitochondrial homeostasis and mediates cardiomyocyte ischemic injury [31]. Specifically, ischemia/reperfusion (I/R) progressively increases CK2α to
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puromycin selection concentration As the primary model we
2021-08-31
As the primary model we selected LDL-receptor knockout mice because these resemble the human plasma lipoprotein profile more closely. Currently, genetic models with reduced milk cholesterol content, which mimic cholesterol-free formula feeding, are unavailable. Thus, instead of modifying milk choles
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br Acknowledgements This work was
2021-08-31
Acknowledgements This work was supported in part by JSPS KAKENHI Grant Number 26292031. Introduction The Cys-loop receptors constitute an important superfamily of ligand-gated ion EPZ015666 (LGICs) and mediate synaptic transmission in both invertebrate and vertebrate nervous systems (Jones e
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The reduction of the calcium response to AVP
2021-08-31
The reduction of the calcium response to AVP could be also due to a PKA-mediated effect of desensitization of IP3R, as described in rat megakaryocytes [41]. Furthermore, PKA activation inhibits intracellular Ca release in mouse pancreatic acinar cells [42] or in rat cerebellum [43]. The phosphorylat
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