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High-throughput virtual screening of novel dihydropyrimidine monastrol analogs reveals robust structure-activity relationship to kinesin Eg5 binding thermodynamics

Shern et al. | Jan 20, 2021

High-throughput virtual screening of novel dihydropyrimidine monastrol analogs reveals robust structure-activity relationship to kinesin Eg5 binding thermodynamics

As cancer continues to take millions of lives worldwide, the need to create effective therapeutics for the disease persists. The kinesin Eg5 assembly motor protein is a promising target for cancer therapeutics as inhibition of this protein leads to cell cycle arrest. Monastrol, a small dihydropyrimidine-based molecule capable of inhibiting the kinesin Eg5 function, has attracted the attention of medicinal chemists with its potency, affinity, and specificity to the highly targeted loop5/α2/α3 allosteric binding pocket. In this work, we employed high-throughput virtual screening (HTVS) to identify potential small molecule Eg5 inhibitors from a designed set of novel dihydropyrimidine analogs structurally similar to monastrol.

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Honey Bee Pollen in Allergic Rhinitis Healing

Bjelajac et al. | Jun 24, 2020

Honey Bee Pollen in Allergic Rhinitis Healing

The most common atopic disease of the upper respiratory tract is allergic rhinitis. It is defined as a chronic inflammatory condition of nasal mucosa due to the effects of one or more allergens and is usually a long-term problem. The purpose of our study was to test the efficiency of apitherapy in allergic rhinitis healing by the application of honey bee pollen. Apitherapy is a branch of alternative medicine that uses honey bee products. Honey bee pollen can act as an allergen and cause new allergy attacks for those who suffer from allergic rhinitis. Conversely, we hoped to prove that smaller ingestion of honey bee pollen on a daily basis would desensitize participants to pollen and thus reduce the severity of allergic rhinitis.

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Heavy Metal Contamination of Hand-Pressed Well Water in HuNan, China

Long et al. | Oct 20, 2019

Heavy Metal Contamination of Hand-Pressed Well Water in HuNan, China

Unprocessed water from hand-pressed wells is still commonly used as a source of drinking water in Chenzhou, the “Nonferrous Metal Village” of China. Long et al. conducted a study to measure the heavy metal contamination levels and potential health effects in this area. Water samples were analyzed through Inductively Coupled Plasma Optical Emission Spectroscopy (ICPOES) and the concentrations of 20 metal elements. Results showed that although none of the samples had dangerous levels of heavy metals, the concentrations of Al, Fe, and Mn in many locations substantially exceeded those suggested in the Chinese Drinking Water Standard and the maximum contaminant levels of Environmental Protection Agency (EPA). The authors have made an important discovery regarding the water safety in HuNan and their suggestions to install water treatment systems would greatly benefit the community.

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Computational development of aryl sulfone compounds as potential NNRTIs

Zhang et al. | Oct 12, 2022

Computational development of aryl sulfone compounds as potential NNRTIs

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors that bind to the HIV reverse transcriptase and prevent replication. Indolyl aryl sulfones (IAS) and IAS derivatives have been found to be highly effective against mutant strains of HIV-1 reverse transcriptase. Here, we analyzed molecules designed using aryl sulfone scaffolds paired to cyclic compounds as potential NNRTIs through the computational design and docking of 100 novel NNRTI candidates. Moreover, we explored the specific combinations of functional groups and aryl sulfones that resulted in the NNRTI candidates with the strongest binding affinity while testing all compounds for carcinogenicity. We hypothesized that the combination of an IAS scaffold and pyrimidine would produce the compounds with the best binding affinity. Our hypothesis was correct as the series of molecules with an IAS scaffold and pyrimidine exhibited the best average binding affinity. Additionally, this study found 32 molecules designed in this procedure with higher or equal binding affinities to the previously successful IAS derivative 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide when docked to HIV-1 reverse transcriptase.

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The non-nutritive sweeteners acesulfame potassium and neotame slow the regeneration rate of planaria

Russo et al. | Nov 29, 2023

The non-nutritive sweeteners acesulfame potassium and neotame slow the regeneration rate of planaria
Image credit: Russo et al. 2023

The consumption of sugar substitute non-nutritive sweeteners (NNS) has dramatically increased in recent years. Despite being advertised as a healthy alternative, NNS have been linked to adverse effects on the body, such as neurodegenerative diseases (NDs). In NDs, neural stem cell function is impaired, which inhibits neuron regeneration. The purpose of this study was to determine if the NNS acesulfame potassium (Ace-K) and neotame affect planaria neuron regeneration rates. Since human neurons may regenerate, planaria, organisms with extensive regenerative capabilities due to stem cells called neoblasts, were used as the model organism. The heads of planaria exposed to either a control or non-toxic concentrations of NNS were amputated. The posterior regions of the planaria were observed every 24 hours to see the following regeneration stages: (1) wound healing, (2) blastema development, (3) growth, and (4) differentiation. The authors hypothesized that exposure to the NNS would slow planaria regeneration rates. The time it took for the planaria in the Ace-K group and the neotame group to reach the second, third, and fourth regeneration stage was significantly greater than that of the control. The results of this study indicated that exposure to the NNS significantly slowed regeneration rates in planaria. This suggests that the NNS may adversely impact neoblast proliferation rates in planaria, implying that it could impair neural stem cell proliferation in humans, which plays a role in NDs. This study may provide insight into the connection between NNS, human neuron regeneration, and NDs.

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Trajectories Between Cigarette Smoking and Electronic Nicotine Delivery System Use Among Adults in the U.S.

Primack et al. | Apr 30, 2020

Trajectories Between Cigarette Smoking and Electronic Nicotine Delivery System Use Among Adults in the U.S.

In this study, the authors characterized the trends of cigarette use amongst people who do and don't use electronic nicotine delivery systems (or ENDS). This was done to help determine if the use of ENDS is aiding in helping smokers quit, as the data on this has been controversial. They found that use of ENDS among people either with or without previous cigarette usage were more likely to continue using cigarettes in the future. This is important information contributing to our understanding of ways to effectively (and not effectively) reduce cigarette use.

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