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Cocktail therapy to inhibit multispecies biofilm in cystic fibrosis patients

Bhat et al. | Sep 22, 2022

Cocktail therapy to inhibit multispecies biofilm in cystic fibrosis patients

Here, recognizing the important role of bacterial biofilms in many life-threatening chronic infections, the authors investigated the effectiveness of a combination treatment on biofilms composed of up to three different common species within the lungs of cystic fibrosis patients with computational analysis. They found that a triple cocktail therapy targeting three different signaling pathways has significant potential as both a treatment and prophylaxis.

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Quantitative definition of chemical synthetic pathway complexity of organic compounds

Baranwal et al. | Jun 19, 2023

Quantitative definition of chemical synthetic pathway complexity of organic compounds

Irrespective of the final application of a molecule, synthetic accessibility is the rate-determining step in discovering and developing novel entities. However, synthetic complexity is challenging to quantify as a single metric, since it is a composite of several measurable metrics, some of which include cost, safety, and availability. Moreover, defining a single synthetic accessibility metric for both natural products and non-natural products poses yet another challenge given the structural distinctions between these two classes of compounds. Here, we propose a model for synthetic accessibility of all chemical compounds, inspired by the Central Limit Theorem, and devise a novel synthetic accessibility metric assessing the overall feasibility of making chemical compounds that has been fitted to a Gaussian distribution.

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Reactivity-informed design, synthesis, and Michael addition kinetics of C-ring andrographolide analogs

Zhou et al. | Nov 17, 2022

Reactivity-informed design, synthesis, and Michael addition kinetics of C-ring andrographolide analogs

Here, based on the identification of androgapholide as a potential therapeutic treatment against cancer, Alzheimer's disease, diabetes, and multiple sclerosis, due to its ability to inhibit a signaling pathway in immune system function, the authors sought ways to optimize the natural product human systems by manipulating its chemical structure. Through the semisynthesis of a natural product along with computational studies, the authors developed an understanding of the kinetic mechanisms of andrographolide and semisynthetic analogs in the context of Michael additions.

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Combinatorial treatment by siNOTCH and retinoic acid decreases A172 brain cancer cell growth

Richardson et al. | Nov 14, 2022

Combinatorial treatment by siNOTCH and retinoic acid decreases A172 brain cancer cell growth

Treatments inhibiting Notch signaling pathways have been explored by researchers as a new approach for the treatment of glioblastoma tumors, which is a fast-growing and aggressive brain tumor. Recently, retinoic acid (RA) therapy, which inhibits Notch signaling, has shown a promising effect on inhibiting glioblastoma progression. RA, which is a metabolite of vitamin A, is very important in embryonic cellular development, which includes the regulation of multiple developmental processes, such as brain neurogenesis. However, high doses of RA treatment caused many side effects such as headaches, nausea, redness around the injection site, or allergic reactions. Therefore, we hypothesized that a combination treatment of RA and siRNA targeting NOTCH1 (siNOTCH1), the essential gene that activates Notch signaling, would effectively inhibit brain cancer cell proliferation. The aim of the study was to determine whether inhibiting NOTCH1 would inhibit the growth of brain cancer cells by cell viability assay. We found that the combination treatment of siNOTCH1 and RA in low concentration effectively decreased the NOTCH1 expression level compared to the individual treatments. However, the combination treatment condition significantly decreased the number of live brain cancer cells only at a low concentration of RA. We anticipate that this novel combination treatment can provide a solution to the side effects of chemotherapy.

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Inhibiting the ERK pathway and the TRPM7 ion channel in gastric and bladder cancer cells

Yang et al. | Oct 14, 2021

Inhibiting the ERK pathway and the TRPM7 ion channel in gastric and bladder cancer cells

In this work the authors investigate new possible treatment methods for gastric and bladder cancers. They specifically targeted the transient receptor potential cation subfamily M member 7 (TRPM7), an ion channel that plays an important role in the survival of both of these cancers, and extracellular regulated kinases (ERKs),which contributes to the carcinogenesis of many cancers including gastric cancer. As a result, the authors consider the effects of Ginsenoside Rd, NS8593, curcumin, and icariin , known to inhibit TRPM7 and ERK. The authors found that these treatments decrease proliferation and induce apoptosis in studies of gastric and bladder cancer cells.

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Combating Insulin Resistance Using Medicinal Plants as a Supplementary Therapy to Metformin in 3T3-L1 Adipocytes: Improving Early Intervention-Based Diabetes Treatment

Jayram et al. | Apr 08, 2019

Combating Insulin Resistance Using Medicinal Plants as a Supplementary Therapy to Metformin in 3T3-L1 Adipocytes: Improving Early Intervention-Based Diabetes Treatment

A primary cause of diabetes is insulin resistance, which is caused by disruption of insulin signal transduction. The objective of this study was to maximize insulin sensitivity by creating a more effective, early intervention-based treatment to avert severe T2D. This treatment combined metformin, “the insulin sensitizer”, and medicinal plants, curcumin, fenugreek, and nettle.

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Using the COmplex PAthway SImulator, Stage Analysis, and Chemical Kinetics to Develop a Novel Solution to Lower Tau Concentrations in Alzheimer’s Disease

Carroll et al. | Sep 28, 2020

Using the COmplex PAthway SImulator, Stage Analysis, and Chemical Kinetics to Develop a Novel Solution to Lower Tau Concentrations in Alzheimer’s Disease

In this study, the authors ask whether a Tau immunotherapy treatment, Hsp70 protein treatment, or dual treatment approach of both the Tau imunotherapy treatment and Hsp70 protein treatment leads to a greater reduction in Tau protein concentration in Alzheimer's disease. Overall, they conclude that the effectiveness of the treatment ultimately relies on the stage of Alzheimer’s.

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Astragalus membranaceus Root Concentration and Exposure Time: Role in Heat Stress Diminution in C. elegans

Chen et al. | Oct 17, 2018

Astragalus membranaceus Root Concentration and Exposure Time: Role in Heat Stress Diminution in <em>C. elegans</em>

In this study, the authors investigated the biological mechanism underlying the actions of a traditional medicinal plant, Astragalus membranaceus. Using C. elegans as an experimental model, they tested the effects of AM root on heat stress responses. Their results suggest that AM root extract may enhance the activity of endogenous pathways that mediate cellular responses to heat stress.

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A Quantitative Assessment of Time, Frequency, and Time-frequency Algorithms for Automated Seizure Detection and Monitoring

Vangal et al. | Sep 28, 2020

A Quantitative Assessment of Time, Frequency, and Time-frequency Algorithms for Automated Seizure Detection and Monitoring

Each year, over 100,000 patients die from Sudden Unexpected Death in Epilepsy (SUDEP). A reliable seizure warning system can help patients stay safe. This work presents a comprehensive, comparative analysis of three different signal processing algorithms for automated seizure/ictal detection. The experimental results show that the proposed methods can be effective for accurate automated seizure detection and monitoring in clinical care.

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