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Application of gene therapy for reversing T-cell dysfunction in cancer

Hyun Lee et al. | Aug 25, 2022

Application of gene therapy for reversing T-cell dysfunction in cancer

Since cancer cells inhibit T-cell activity, the authors investigated a method to reverse T-cell disfunction with gene therapy, so that the T-cells would become effective once again in fighting cancer cells. They used the inhibition of proprotein convertases (PCSK1) in T cells and programmed death-ligand 1 (CD274) in cancer cells. They observed the recovery of IL-2 expression in Jurkat cells, with increased recovery noted in a co-culture sample. This study suggests a novel strategy to reactivate T cells.

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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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Upregulation of the Ribosomal Pathway as a Potential Blood-Based Genetic Biomarker for Comorbid Major Depressive Disorder (MDD) and PTSD

Ravi et al. | Aug 22, 2018

Upregulation of the Ribosomal Pathway as a Potential  Blood-Based Genetic Biomarker for Comorbid Major Depressive Disorder (MDD) and PTSD

Major Depressive Disorder (MDD), and Post-Traumatic Stress Disorder (PTSD) are two of the fastest growing comorbid diseases in the world. Using publicly available datasets from the National Institute for Biotechnology Information (NCBI), Ravi and Lee conducted a differential gene expression analysis using 184 blood samples from either control individuals or individuals with comorbid MDD and PTSD. As a result, the authors identified 253 highly differentially-expressed genes, with enrichment for proteins in the gene ontology group 'Ribosomal Pathway'. These genes may be used as blood-based biomarkers for susceptibility to MDD or PTSD, and to tailor treatments within a personalized medicine regime.

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Isolation of Microbes From Common Household Surfaces

Gajanan et al. | Jan 27, 2013

Isolation of Microbes From Common Household Surfaces

Microorganisms such as bacteria and fungi live everywhere in the world around us. The authors here demonstrate that these predominantly harmless microbes can be isolated from many household locations that appear "clean." Further, they test the cleaning power of 70% ethanol and suggest that many "clean" surfaces are not in fact "sterile."

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How visualization influences strength endurance

Moore et al. | Jul 06, 2022

How visualization influences strength endurance

Recognizing a potential link between mental focus and physical endurance, here, the authors considered the effects of mental visualization on strength endurance. By comparing the number of repetitions completed in sets where the lifter was aware of the weight to be lifted against sets where the lifter was kept unaware, they found that the lifter was able to maintain strength endurance when unable to accurately visualize the weight they lifted in this exploratory study.

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Pancreatic Adenocarcinoma: An Analysis of Drug Therapy Options through Interaction Maps and Graph Theory

Gupta et al. | Feb 04, 2014

Pancreatic Adenocarcinoma: An Analysis of Drug Therapy Options through Interaction Maps and Graph Theory

Cancer is often caused by improper function of a few proteins, and sometimes it takes only a few proteins to malfunction to cause drastic changes in cells. Here the authors look at the genes that were mutated in patients with a type of pancreatic cancer to identify proteins that are important in causing cancer. They also determined which proteins currently lack effective treatment, and suggest that certain proteins (named KRAS, CDKN2A, and RBBP8) are the most important candidates for developing drugs to treat pancreatic cancer.

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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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Fluorescein or Green Fluorescent Protein: Is It Possible to Create a Sensor for Dehydration?

Joshi et al. | Dec 09, 2019

Fluorescein or Green Fluorescent Protein: Is It Possible to Create a Sensor for Dehydration?

Currently there is no early dehydration detection system using temperature and pH as indicators. A sensor could alert the wearer and others of low hydration levels, which would normally be difficult to catch prior to more serious complications resulting from dehydration. In this study, a protein fluorophore, green fluorescent protein (GFP), and a chemical fluorophore, fluorescein, were tested for a change in fluorescence in response to increased temperature or decreased pH. Reversing the pH change did not restore GFP fluorescence, but that of fluorescein was re-established. This finding suggests that fluorescein could be used as a reusable sensor for a dehydration-related pH change.

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Association of agenesis of the corpus callosum with epilepsy and anticonvulsant drug treatment

Steger et al. | Feb 21, 2023

Association of agenesis of the corpus callosum with epilepsy and anticonvulsant drug treatment
Image credit: Robina Weermeijer on Unsplash

Agenesis of the Corpus Callosum (ACC) is a birth defect where an infant’s corpus callosum, the structure linking the brain’s two hemispheres to allow interhemispheric communication, fails to develop in a typical manner during pregnancy. Existing research on the connection between ACC and epilepsy leaves significant gaps, due to the lack of focused investigation. One important gap is the degree to which ACC may impact the course of epilepsy treatment and outcomes. The present study was conducted to test the hypotheses that epilepsy is highly prevalent among individuals with ACC, and that those with both ACC and epilepsy have a lower response rate to anticonvulsant drugs than other patients treated with anticonvulsant drugs. A weighted average of epilepsy rates was calculated from a review of existing literature, which supported the hypothesis that epilepsy was more common among individuals with ACC (25.11%) than in the general population (1.2%). An empirical survey administered to 57 subjects or parents of subjects showed that rate of intractable epilepsy among study subjects with both ACC and epilepsy was substantially higher than the rate found in the general population, indicating that individuals with both conditions had a lower response rate to the anticonvulsant drugs. This study contributes novel results regarding the potential for concurrence of ACC and epilepsy to interfere with anticonvulsant drug treatment. We also discuss implications for how medical professionals may use the findings of this study to add depth to their treatment decisions.

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