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Multi targeting agents are of major interest in modern drug
2022-04-11

Multi-targeting agents are of major interest in modern drug design and discovery. Design of such compounds can be applied to H3R antagonists for the purpose of achieving optimum efficiency as performed for some preclinical candidates such as recently for contilisant (Bautista-Aguilera et al., 2017;
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This crosstalk may be responsible for the
2022-04-11

This crosstalk may be responsible for the beneficial effects of histamine H2 receptor inverse agonists on Manidipine 2HCl pathologies and may also explain unwanted effects of these drugs on other tissues. In this way, Allen et al. reported an anaphylactoid reaction following cessation of high-dose
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br Methods br Results br Discussion Exercise
2022-04-11

Methods Results Discussion Exercise results in a remarkable redistribution of blood flow, which increases in active skeletal muscles but decreases in the splanchnic circulation. The regional blood flow in the kidney, spleen, stomach and intestine was measured by using the microsphere techni
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Dormancy is a physiological state when
2022-04-11

Dormancy is a physiological state when viable seeds do not germinate. Seed stratification, a commonly used technique, is used for dormancy removal and can be performed in moisture for an experimentally revealed time at warm or cold temperatures. All conditions depends on plant species (Dębska et al.
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We previously evaluated the immuno modulatory
2022-04-11

We previously evaluated the immuno-modulatory efficacy of GSNO in different EAE models and reported prophylactic and therapeutic efficacy of GSNO against the clinical disease of EAE [22], [36]. GSNO inhibited the IL-6-induced STAT3 activation (Tyr705 phosphorylation) by S-nitrosylation of the STAT3
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br Results and discussion br Conclusions
2022-04-11

Results and discussion Conclusions In summary, we generated analogues of the hit compounds 1–3, studied their structure–activity relationships, and created a series of highly potent GPR55 agonists. The most potent agonists among the series were 17a-b, 17e, 17g and 17l with EC50 values below 10
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In summary our findings support the hypothesis
2022-04-11

In summary, our findings support the hypothesis that activation of GPR55 protects against deficits in neurogenesis induced by inflammatory insult both in vitro and in vivo through direct targeting of NSCs. Better understanding of the mechanisms by which GPR55 provides neuroprotection is critically n
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Our last area of exploration was the piperidine core as
2022-04-11

Our last area of exploration was the piperidine core as shown in . We rationalised that the basicity of the nitrogen (measured p=7.0) may be responsible for the affinity for the hERG receptor and we therefore sought to moderate this by incorporation of electronegative groups at the 3-position. To th
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To test our refinement protocol we considered a
2022-04-11

To test our refinement protocol, we considered a benchmark set of 12 N-linked glycan-containing protein structures determined by X-ray crystallography at resolutions ranging between 1.9 Å and 3.5 Å and comprising a total of 133 glycan units. We identified four incorrect anomeric configurations and 2
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br Introduction Atherothrombosis is associated
2022-04-11

Introduction Atherothrombosis is associated with the presence of a low-grade, subclinical smoldering inflammatory response [1]. Several inflammatory markers, among them high-sensitive C-reactive protein (hs-CRP) [2], the erythrocyte sedimentation rate (ESR) [3], fibrinogen concentrations [4], int
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The lactam compounds including ceftriaxone CEF have shown
2022-04-11

The β-lactam compounds, including ceftriaxone (CEF), have shown to attenuate drug-seeking in several drugs of abuse including methamphetamine [31], cocaine [32,33], nicotine [34] and morphine [35]. Moreover, in our laboratory, we have shown that CEF can reduce chronic alcohol drinking via upregulati
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A pooled overall survival analysis at year
2022-04-09

A pooled overall survival analysis at 1year showed no difference in survival between the two study arms, although these studies were not designed or powered to demonstrate a survival benefit. Among the 979 total patients in both ROMANA 1 and 2, about 55% continued on to the ROMANA 3 trial. That tria
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Amongst oxidants that we have studied
2022-04-09

Amongst oxidants that we have studied, PMS is unique in having a greater effect in deoxygenated cells. The resulting phenotype shows some similarities with the increased cation permeability shown by deoxygenated sickle Riboflavin [27]. It is interesting to consider why PMS has this effect. PMS func
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In an immunohistochemical analysis of gastric cancer samples
2022-04-09

In an immunohistochemical analysis of 117 gastric cancer samples, reduced Cx43 and E-cadherin expression were shown to contribute to the development of primary gastric cancer; however, increased Cx43 and E-cadherin expression contributed to lymph node metastasis [13]. In primary urothelial Safingol
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These observations are of particular interest in the
2022-04-09

These observations are of particular interest in the context of recent conceptual changes regarding the mechanisms by which different types of leukocytes contribute to atherogenesis. Over the last decade, the paradigm of the predominant circulatory origin of lesional macrophages has been challenged
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