Curating the gnomAD database: Report of novel variants in the thyroid peroxidase gene using in silico bioinformatics algorithms and a literature review

Molina, Maricel F.; Pio, Mauricio Gomes; Scheps, Karen G.; Adrover, Ezequiela; Abelleyro, Miguel Martín; Targovnik, Héctor M.; Rivolta, Carina M.

doi:10.1016/j.mce.2022.111748

Cited by 2 publications

(1 citation statement)

References 141 publications

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“…NR-DBD, LR-DBD superfamilies, ABC1 and HX domains play crucial role in cellular and molecular response such as nuclear receptors, transcriptional regulation and hormone sensing (Abdullah‐Zawawi et al 2021). Hormone_recep and An_peroxidase domains are involve in molecular and biological functions like gene expression and oxidative stress (Molina et al 2022 ). Peptidase_M10 and PDGF superfamilies domains are involve in cell signaling, immune response and extracellular matrix remodeling (Nageswara et al 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species

Shahzadi,

Yousaf,

Anjum

et al. 2024

Bioresour. Bioprocess.

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Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, and Epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein–protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, −7.1, −9.0 and −8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that C. fistula (Dihydrokaempferol, Flavan-3-ol) and C. occidentalis (Germichrysone) have potential therapeutic active constituents to treat hypertension and in future novel drug formulation. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%