The clinically used glitazones (rosiglitazone and pioglitazone) for type 2 diabetes mellitus therapy have been linked to serious side effects such as fluid retention, congestive heart failure, weight gain, bone loss, and an increased risk of bladder cancer. The complete activation of PPAR-γ receptors in target tissues is linked to these effects. Many studies have demonstrated that partial PPAR-γ activators (GW0072, PAT5A, GQ16) give equivalent therapeutic benefits to full PPAR-γ agonists without the associated side effects. These breakthroughs cleared the path for the development of partial agonists or selective PPAR-γ modulators (SPPARγMs). This study combined pharmacophore modeling, molecular docking, and an adipogenesis experiment to identify thiazolidine analogs as SPPARMs/partial agonists. A custom library of 220 molecules was created and virtual screened to discover 90 compounds as SPPARγMs/ partial agonists. The chosen eight compounds were synthesized and tested for adipogenesis using 3T3L1 cell lines. These compounds' partial agonistic activity was evaluated in 3T3L1 cell lines by comparing their capacity to stimulate PPAR-γ mediated adipogenesis to that of a full agonist, rosiglitazone. The findings of the adipogenesis experiment demonstrate that all eight compounds examined had a partial potential to stimulate adipogenesis when compared to the full agonist, rosiglitazone. The current investigation identified eight possible PPAR-γ partial agonists or SPPARγMs that may be effective in the treatment of type 2 diabetes mellitus.

2019-01-01·Journal of Clinical and Experimental Dentistry

Does comsumption of staining drinks compromise the result of tooth whitening?

Article

作者: Dias, Marlon-Ferreira ; Lins-Filho, Paulo-Cardoso ; Silva, Marianna-Falcão ; Guimarães, Renata-Pedrosa ; Nogueira, Jhones-Suelone-Pontes

BACKGROUNDAfter dental bleaching procedures dentists commonly advise patients to reduce the consumption of beverages that may cause the teeth to stain, however, the effectiveness of teeth whitening may not be directly affected by diet.MATERIAL AND METHODSIt was evaluated through in vitro study whether contact with dyes through in-office bleaching sessions with 35% hydrogen peroxide would influence the effectiveness of treatment. Sixty bovine incisors were randomly assigned into 5 groups (n = 12) according to contact frequency and type of dye solutions. All dental elements received three in-office bleaching sessions with 35% hydrogen peroxide one week apart. Except for GCTRL (control), all experimental groups were submerged in dyes (coffee or wine) for 5 min once a day. In groups GC24 and GW24 contact with the dyes was made from 24 hours after each bleaching session, while in groups GC72 and GW72, from 72 hours. The color was measured with a digital spectrophotometer. Data were expressed as statistics: mean and standard deviation.RESULTSContact with dyes during in-office bleaching treatment with 35% hydrogen peroxide did not influence the staining averages after three bleaching sessions. The speed of the whitening effect was influenced by contact with coffee from 24 hours after the sessions and with wine from 24 hours and 72 hours after the whitening session. The whitening result was reversed after one week for all groups, especially for groups that came in contact with red wine either 24 hours or 72 hours after session and coffee after 24 hours.CONCLUSIONSContact with dyes during in-office bleaching treatment did not influence the final staining averages after three bleaching sessions although there was influence on speed of the whitening effect between the sessions. Key words:Tooth bleaching, hydrogen peroxide, spectrophotometry.

2015-11-01·Journal of Computer-Aided Molecular Design3区 · 生物学

Extracting ligands from receptors by reversed targeted molecular dynamics

3区 · 生物学

Article

作者: Wolf, Romain M

Short targeted MD trajectories are used to expel ligands from binding sites. The expulsion is governed by a linear increase of the target RMSD value, growing from zero to an arbitrary chosen final RMSD that forces the ligand to a selected distance outside of the receptor. The RMSD lag (i.e., the difference between the imposed and the actual RMSD) can be used to follow barriers encountered by the ligand during its way out of the receptor. The force constant used for the targeted MD can transform the RMSD lag into a strain energy. Integration of the (time-dependent) strain energy over time yields a value with the dimensions of "action" (i.e, energy multiplied by time) and can serve as a measure for the overall effort required to extract the ligand from its binding site. Possibilities to compare (numerically and graphically) the randomly detected exit pathways are discussed. As an example, the method is tested on the exit of bisphenol A from the human estrogen-related receptor [Formula: see text] and of GW0072 from the peroxysome proliferator activated receptor.

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