Uncovering the Molecular Mechanism of Actions between Pharmaceuticals and Proteins on the AD Network

<div><p>This study begins with constructing the mini metabolic networks (MMNs) of beta amyloid (Aβ) and acetylcholine (ACh) which stimulate the Alzheimer’s Disease (AD). Then we generate the AD network by incorporating MMNs of Aβ and ACh, and other MMNs of stimuli of AD. The panel of proteins contains 49 enzymes/receptors on the AD network which have the 3D-structure in PDB. The panel of drugs is formed by 5 AD drugs and 5 AD nutraceutical drugs, and 20 non-AD drugs. All of these complexes formed by these 30 drugs and 49 proteins are transformed into dyadic arrays. Utilizing the prior knowledge learned from the drug panel, we propose a statistical classification (dry-lab). According to the wet-lab for the complex of amiloride and insulin degrading enzyme, and the complex of amiloride and neutral endopeptidase, we are confident that this dry-lab is reliable. As the consequences of the dry-lab, we discover many interesting implications. Especially, we show that possible causes of Tacrine, donepezil, galantamine and huperzine A cannot improve the level of ACh which is against to their original design purpose but they still prevent AD to be worse as Aβ deposition appeared. On the other hand, we recommend Miglitol and Atenolol as the safe and potent drugs to improve the level of ACh before Aβ deposition appearing. Moreover, some nutrients such as NADH and Vitamin E should be controlled because they may harm health if being used in wrong way and wrong time. Anyway, the insights shown in this study are valuable to be developed further.</p></div

The derived data regarding similarity and free energy based on mean <i>m</i> and standard deviation <i>σ</i>.

<p>The derived data regarding similarity and free energy based on mean <i>m</i> and standard deviation <i>σ</i>.</p

(A) The general form of MMN of a stimulus. (B) The MMN of Aβ. (C) The MMN of ACh. (D) The MMN of tau protein.

<p>The stimuli (middle products), enzymes, and receptors are highlighted with red, orange, and green colors, respectively.</p

The values of similarity and free energy based on 30 drugs on their targets.

<p>In which <i>x</i>₁ is the value of similarity output from ILbind, and <i>x</i>₂ is the minimal free energy output from VINA for each complex formed by a drug and a protein ranging to the panels</p

The inhibition rate and quenching efficiency and value of IC50 for 5-(N, N-Dimethyl) amiloride hydrochloride and amiloride HCl dehydrate binding to IDE and NEP compared with its controlling drug Bacitracin A and DL-Thiophan, respectively.

<p>The inhibition rate and quenching efficiency and value of IC50 for 5-(N, N-Dimethyl) amiloride hydrochloride and amiloride HCl dehydrate binding to IDE and NEP compared with its controlling drug Bacitracin A and DL-Thiophan, respectively.</p

(A) COX-2 complexes in the NSAIDs only. (B) COX-2 complexes in the NSAIDs and NAI. (C) ACE in complex with the intrinsic ligands only. (D) ACE in complex with the intrinsic ligands and NAI.

<p>(A) COX-2 complexes in the NSAIDs only. (B) COX-2 complexes in the NSAIDs and NAI. (C) ACE in complex with the intrinsic ligands only. (D) ACE in complex with the intrinsic ligands and NAI.</p

The AD network generated based on three mini metabolic networks.

<p>For clearly understanding this graph, we state the nodes and edges as follows: enzymes, stimuli, precursors and receptors are the nodes. In which, enzymes are shown by orange ovals, stimuli and their precursors are shown by cyan boxes, and receptors are shown by green ovals. The edges are consisted of three kinds of arrows. In which, green arrows with “+” indicates the up-regulating or activating relationship, while blue arrows with “–” means the down-regulating or inhibiting relationship. The black arrows are the normal up- and down- stream relationship.</p

The seven areas (H₀- H₆) of complexes to be recommended or rejected.

<p>H₀ is colored with red, H₁ is colored with orange, H₂ is colored with yellow, H₃ is colored with green. H₄ is colored with blue, H₅ is colored with purple, and H₆ is blank.</p

Cavum septum pellucidum and first-episode psychosis: A meta-analysis

<div><p>Objectives</p><p>To investigate the prevalence and changes of cavum septum pellucidum (CSP) in first-episode psychosis (FEP) patients.</p><p>Methods</p><p>Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify eligible studies comparing FEP patients and healthy controls from inception to Feb 29, 2016.</p><p>Results</p><p>Ten cross-sectional studies and three longitudinal studies reported in ten articles met our criteria. Our meta-analysis found no significant differences in the prevalence of either “any CSP” (OR = 1.41; 95% CI 0.90–2.20; p = 0.13; I² = 52.7%) or “large CSP” (OR = 1.10; 95% CI 0.77–1.58; p = 0.59; I² = 24.1%) between FEP patients and healthy controls. However, the heterogeneity analysis of the prevalence of “any CSP” suggested bias in outcome reporting.</p><p>Conclusions</p><p>The results based on current evidence suggest it is unclear whether “any CSP” is a risk factor for FEP due to the heterogeneity of the studies. There is insufficient evidence to support that “large CSP” is a possible risk factor for FEP.</p></div

Recognition by spectrum of simple groups C (p) (2)

It is proved that, if G is a finite group that has the same set of element orders as the simple group Cp(2) for prime p &gt; 3, then G/O2(G) is isomorphic to Cp(2). © 2012 Pleiades Publishing, Ltd