21 research outputs found
Molecular level activation insights from a NR2A/NR2B agonist
<div><p>N-methyl D-aspartate receptors (NMDARs), a subclass of glutamate receptors have broad actions in neural transmission for major brain functions. Overactivation of NMDARs leading to “excitotoxicity” is the underlying mechanism of neuronal death in a number of neurological diseases, especially stroke. Much research effort has been directed toward developing pharmacological agents to modulate NMDAR actions for treating neurological diseases, in particular stroke. Here, we report that Alliin, a sulfoxide in fresh garlic, exhibits affinity toward NR2A as well as NR2B receptors based on virtual screening. Biological activities of Alliin on these two receptors were confirmed in electrophysiological studies. Ligand-binding site closure, a structural change precluding ion channel opening, was observed with Alliin during 100 ns molecular dynamics simulation. Alliin interactions with NR2A and NR2B suggest that residues E/A413, H485, T690, and Y730 may play important roles in the conformation shift. Activation of NR2A and NR2B by Alliin can be differentiated from that caused by glutamate, the endogenous neurotransmitter. These characteristic molecular features in NR2A and NR2B activation provide insight into structural requirements for future development of novel drugs with selective interaction with NR2A and NR2B for treating neurological diseases, particularly stroke.</p></div
Distributions of the demographic characteristics and the comorbid diseases between patients with and without Parkinson’s disease (PD) and their crude odds ratios.
<p>Distributions of the demographic characteristics and the comorbid diseases between patients with and without Parkinson’s disease (PD) and their crude odds ratios.</p
The adjusted odds ratios (95% CIs) of PM10 exposure for a later PD onset in subjects with and without any comorbid diseases, and in all subjects.
<p>The adjusted odds ratios (95% CIs) of PM10 exposure for a later PD onset in subjects with and without any comorbid diseases, and in all subjects.</p
The adjusted odds ratios of the exposure to PM<sub>10</sub> and a later PD onset by comorbid diseases.
<p>Ref: T1 level (PM<sub>10</sub> ≤ 54 μg/m<sup>3</sup>; OR = 1). *: P < 0.05; **: P < 0.01; ***: P < 0.001.</p
Distributions of demographic variables and comorbidities in breast cancer patients with and without propensity score matching.
<p>Distributions of demographic variables and comorbidities in breast cancer patients with and without propensity score matching.</p
Crude and adjusted hazard ratios and 95% confidence intervals of the incidence of acute pancreatitis in tamoxifen users and nonusers according to a time-dependent Cox regression model without propensity score matching.
<p>Crude and adjusted hazard ratios and 95% confidence intervals of the incidence of acute pancreatitis in tamoxifen users and nonusers according to a time-dependent Cox regression model without propensity score matching.</p
Baseline characteristics of the septicaemia group and the control cohort.
†<p>ICD9 003.1, 036.2 & 038.</p><p>Chi-square test.</p
Hazard ratios for the development of stroke associated with septicaemia by age and gender.
<p>HR: hazard ratio, CI: confidence interval; *<i>p</i><0.05; **<i>p</i><0.01; ***<i>p</i><0.001.</p><p>The interaction <i>p</i> between age and septicaemia was <0.05 for all strokes, ischaemic and haemorrhagic stroke.</p><p>The interaction <i>p</i> between gender and septicaemia was 0.042 for haemorrhagic stroke but interaction <i>p</i> for all strokes and ischaemic stroke was >0.05.</p
Hazard ratios for development of stroke associated with septicaemia.
<p>HR: hazard ratio, CI: confidence interval.</p><p>*<i>p</i><0.05; **<i>p</i><0.01; ***<i>p</i><0.001.</p