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Developing anticholinergic drugs for the treatment of asthma with improved efficacy

Wong et al. | Jul 05, 2023

Developing anticholinergic drugs for the treatment of asthma with improved efficacy
Image credit: Wong et al.

Anticholinergics are used in treating asthma, a chronic inflammation of the airways. These drugs block human M1 and M2 muscarinic acetylcholine receptors, inhibiting bronchoconstriction. However, studies have reported complications of anticholinergic usage, such as exacerbated eosinophil production and worsened urinary retention. Modification of known anticholinergics using bioisosteric replacements to increase efficacy could potentially minimize these complications. The present study focuses on identifying viable analogs of anticholinergics to improve binding energy to the receptors compared to current treatment options. Glycopyrrolate (G), ipratropium (IB), and tiotropium bromide (TB) were chosen as parent drugs of interest, due to the presence of common functional groups within the molecules, specifically esters and alcohols. Docking score analysis via AutoDock Vina was used to evaluate the binding energy between drug analogs and the muscarinic acetylcholine receptors. The final results suggest that G-A3, IB-A3, and TB-A1 are the most viable analogs, as binding energy was improved when compared to the parent drug. G-A4, IB-A4, IB-A5, TB-A3, and TB-A4 are also potential candidates, although there were slight regressions in binding energy to both muscarinic receptors for these analogs. By researching the effects of bioisosteric replacements of current anticholinergics, it is evident that there is a potential to provide asthmatics with more effective treatment options.

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Substance Abuse Transmission-Impact of Parental Exposure to Nicotine/Alcohol on Regenerated Planaria Offspring

Bennet et al. | Jul 02, 2024

Substance Abuse Transmission-Impact of Parental Exposure to Nicotine/Alcohol on Regenerated Planaria Offspring

The global mental health crisis has led to increased substance abuse among youth. Prescription drug abuse causes approximately 115 American deaths daily. Understanding intergenerational transmission of substance abuse is complex due to lengthy human studies and socioeconomic variables. Recent FDA guidelines mandate abuse liability testing for neuro-active drugs but overlook intergenerational transfer. Brown planaria, due to their nervous system development similarities with mammals, offer a novel model.

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Enhancing activity of antibiotics against Staphylococcus aureus with Shuang-Huang-Lian

Liu et al. | Sep 29, 2022

Enhancing activity of antibiotics against Staphylococcus aureus with Shuang-Huang-Lian

Staphylococcus aureus is a major pathogen in both hospitals and the community and can cause systemic infections such as pneumonia. Multi-drug resistant strains, such as Methicillin-resistant S. aureus (MRSA) are particularly worrisome. In order to reduce the development of bacterial resistance, we hypothesized that two selected traditional Chinese medicines, Shuang-Huang-Lian (SHL) and Lan-Qin, would be effective against S. aureus. The results showed that SHL had a synergistic effect with gentamicin as well as additive effects with penicillin and cefazolin against S. aureus compared with using antibiotics alone.

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The Effects of Ezetimibe on Triglyceride and Alanine Transaminase Reduction in Drosophila Melanogaster Model of Nonalcoholic Fatty Liver Disease (NAFLD)

Dania et al. | Apr 30, 2020

The Effects of Ezetimibe on Triglyceride and Alanine Transaminase Reduction in <i>Drosophila Melanogaster</i> Model of Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic Fatty Liver Disease (NAFLD) is a condition where a surplus of triglycerides or fat are present in the liver. In this study, ezetimibe, a cholesterol lowering drug, was used to treat flies modeling NAFLD. Compared to the coconut oil fed flies that were transferred to the control medium, the flies transferred to the control medium treated with ezetimibe showed a decrease in their triglyceride and alanine transaminase level.

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The Role of Temporal Lobe Epilepsy in Cardiac Structure and Function

Choi et al. | Aug 15, 2018

The Role of Temporal Lobe Epilepsy in Cardiac Structure and Function

Cardiac autonomic and structural changes may occur in temporal lobe epilepsy patients and contribute to the risk of sudden unexpected death in epilepsy patients. Choi and colleagues reviewed clinical charts to obtain patients’ lifetime seizure count, antiepileptic drug use, and history of heart disease, followed by transthoracic echocardiogram to calculate left ventricle dimensions, ejection fraction, and left ventricle mass. By comparing epilepsy patients to control subjects, they found that epilepsy patients had thinner left ventricle walls and smaller ejection fraction, but with no significant difference in left ventricle mass.

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The effect of bioenhancers on ampicillin-sulbactam as a treatment against A. baumannii

Balaji et al. | Sep 21, 2024

The effect of bioenhancers on ampicillin-sulbactam as a treatment against <i>A. baumannii<i>

This article explores the potential of piperine, a bioenhancer from black pepper, to improve antibiotic efficacy against antibiotic-resistant Acinetobacter baumannii. By combining piperine with ampicillin-sulbactam, the study demonstrated a significant reduction in bacterial growth for most strains tested, showcasing the promise of bioenhancers in combating resistant pathogens. This research highlights the possibility of reducing the required antibiotic dosage, potentially offering a new strategy in the fight against drug-resistant bacteria.

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A Novel Alzheimer's Disease Therapeutic Model: Attenuating Hyperphosphorylated Tau and Amyloid β (Aβ) Aggregates by Characterizing Antioxidative, Anti-Inflammatory, and Neuroprotective Properties of Natural Extracts

Pokkunuri et al. | Jul 25, 2022

A Novel Alzheimer's Disease Therapeutic Model: Attenuating Hyperphosphorylated Tau and Amyloid β (Aβ) Aggregates by Characterizing Antioxidative, Anti-Inflammatory, and Neuroprotective Properties of Natural Extracts

Oxidative damage and neuro-inflammation were the key pathways implicated in the pathogenesis of Alzheimer’s disease. In this study, 30 natural extracts from plant roots and leaves with extensive anti-inflammatory and anti-oxidative properties were consumed by Drosophila melanogaster. Several assays were performed to evaluate the efficacy of these combinational extracts on delaying the progression of Alzheimer’s disease. The experimental group showed increased motor activity, improved associative memory, and decreased lifespan decline relative to the control group.

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Effect of Natural Compounds Curcumin and Nicotinamide on α-synuclein Accumulation in a C. elegans Model of Parkinson’s Disease

Mehrotra et al. | Jan 29, 2018

Effect of Natural Compounds Curcumin and Nicotinamide on α-synuclein Accumulation in a C. elegans Model of Parkinson’s Disease

Parkinson's disease is a neurodegenerative disorder that affects over 10 million people worldwide. It is caused by destruction of dopamine-producing neurons, which results in severe motor and movement symptoms. In this study, the authors investigated the anti-Parkinsonian effects of two natural compounds curcumin and nicotinamide using C. elegans as a model organism.

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