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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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Interleukin family (IL-2 and IL-1β) as predictive biomarkers in Indian cancer patients: A proof of concept study

Parthasarathy et al. | Apr 03, 2023

Interleukin family (IL-2 and IL-1β) as predictive biomarkers in Indian cancer patients: A proof of concept study
Image credit: National Cancer Institute

Here, recognizing that the immune response to cancer results in biomarkers that can be used to assess the immune status of cancer patients, the authors investigated the concentrations of key cytokines (TH1 and TH2 cytokines) in healthy controls and cancer patients. They identified significant changes in resting and activated cytokine profiles, suggesting that data of biomarkers such as these could serve as a starting point for further treatment with regard to a patient's specific immune profile.

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Impact of daf-25 and daf-11 Mutations on Olfactory Function in C. elegans

Gardner et al. | Feb 02, 2019

Impact of daf-25 and daf-11 Mutations on Olfactory Function in C. elegans

Cilia are little hair-like protrusions on many cells in the human body, including those lining the trachea where they play a role in clearing our respiratory tract of mucous and other irritants. Genetic mutations that impair ciliary function have serious consequences on our well-being making it important to understand how ciliary function is regulated. By using a simple organism, such as the worm C. elegans that use cilia to move, the authors explore the effect of certain genetic mutations on the cilia of the worms by measuring their ability to move towards or away from certain odorants.

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How does light affect the distribution of Euglena sp. and Tetrahymena pyriformis

Singh et al. | Mar 03, 2022

How does light affect the distribution of <em>Euglena sp.</em> and <em>Tetrahymena pyriformis</em>

In this article, the authors explored the locomotory movement of Euglena sp. and Tetrahymena pyriformis in response to light. Such research bears relevance to the migration and distribution patterns of both T. pyriformis and Euglena as they differ in their method of finding sustenance in their native environments. With little previous research done on the exploration of a potential response to photostimulation enacted by T. pyriformis, the authors found that T. pyriformis do not bias in distribution towards areas of light - unlike Euglena, which displayed an increased prevalence in areas of light.

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Modular mimics of neuroactive alkaloids - design, synthesis, and cholinesterase inhibitory activity of rivastigmine analogs

Yu et al. | Sep 12, 2022

Modular mimics of neuroactive alkaloids - design, synthesis, and cholinesterase inhibitory activity of rivastigmine analogs

Naturally occurring neuroactive alkaloids are often studied for their potential to treat Neurological diseases. This team of students study Rivastigmine, a potent cholinesterase inhibitor that is a synthetic analog of physostigmine, which comes from the Calabar bean plant Physostigma venenosum. By comparing the effects of optimized synthetic analogs to the naturally occurring alkaloid, they determine the most favorable analog for inhibition of acetylcholinesterase (AChE), the enzyme that breaks down the neurotransmitter acetylcholine (ACh) to terminate neuronal transmission and signaling between synapses.

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Developing novel plant waste-based hydrogels for skin regeneration and infection detection in diabetic wounds

Mathew et al. | Aug 10, 2023

Developing novel plant waste-based hydrogels for skin regeneration and infection detection in diabetic wounds

The purpose of this investigation is to develop a hydrogel to aid skin regeneration by creating an extracellular matrix for fibroblast growth with antibacterial and infection-detection properties. Authors developed two natural hydrogels based on pectin and potato peels and characterized the gels for fibroblast compatibility through rheology, scanning electron microscopy, swelling, degradation, and cell cytotoxicity assays. Overall, this experiment fabricated various hydrogels capable of acting as skin substitutes and counteracting infections to facilitate wound healing. Following further testing and validation, these hydrogels could help alleviate the 13-billion-dollar financial burden of foot ulcer treatment.

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Toxicity of aminomethylphosphonic acid via the Wnt signaling pathway as a novel mechanism

Zhuang et al. | Mar 08, 2023

Toxicity of aminomethylphosphonic acid via the Wnt signaling pathway as a novel mechanism
Image credit: Image credit: Dapur Melodi

The Wnt signaling pathway, known to coordinate important aspects of cellular homeostasis ranging from differentiation, proliferation, migration, and much more, is dysregulated in many human diseases. This study demonstrates that aminomethylphosphonic acid, which is the main metabolite found in the common herbicide Glyphosate, is toxic to planaria and capable of binding to canonical Wnt proteins.

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In vitro Comparison of Anticancer and Immunomodulatory Activities of Resveratrol and its Oligomers

Zhang et al. | Sep 02, 2020

<em>In vitro</em> Comparison of Anticancer and Immunomodulatory Activities of Resveratrol and its Oligomers

Resveratrol is a type of stillbenoid, a phenolic compound produced in plants, that is known for its anti-inflammatory and anticancer effects. Many oligomers of resveratrol have recently been isolated their bioactivities remain unknown. Here, authors compared the bioactivities of resveratrol with natural dimers (ε-viniferin and gnetin H) and trimers (suffruticosol B and C). Results provide preliminary evidence that resveratrol oligomers could be potential preventive or therapeutic agents for cancers and other immune-related diseases

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