NAD_MCNN: Combining Protein Language Models and Multiwindow Convolutional Neural Networks for Deacetylase NAD+ Binding Site Prediction DOI
Van‐The Le, Yuchen Liu,

Yan‐Yun Chang

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(4)

Published: April 1, 2025

Sirtuins, a class of NAD+ -dependent deacetylases, play key role in aging, metabolism, and longevity. Their interaction with at the catalytic site is crucial for function, but experimental methods to map binding sites are time consuming. To address this, we developed computational method integrating pretrained protein language models multiwindow convolutional neural networks (CNNs). This captures sequence information diverse local patterns, achieving state-of-the-art performance, AUC 0.9733 human sirtuin proteins 0.9701 other NAD-dependent deacylation enzymes. These findings offer insights into sirtuins aging their broader biological functions while providing new path identifying therapeutic targets aging-related diseases.

Language: Английский

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3 DOI Creative Commons
Wei Zhang,

Zhixing Fan,

Fengyuan Wang

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 23

Published: Jan. 14, 2023

Cardiotoxicity linked to doxorubicin (DOX) is primarily caused by inflammation, oxidative stress, and apoptosis. The role of tubeimoside I (TBM) in DOX-induced cardiotoxicity remains ambiguous, despite growing evidence that it could reduce apoptosis various diseases. This study was designed investigate the TBM uncover underlying mechanisms. H9c2 cell line C57BL/6 mice were used construct an vitro vivo model myocardial injury, respectively. We observed DOX treatment provoked cardiomyocyte apoptosis, which significantly alleviated administration. Mechanistically, attenuated downregulation sirtuin 3 (SIRT3), SIRT3 inhibition abrogated beneficial effects both vivo. In conclusion, eased increasing expression SIRT3, suggesting holds great promise for treating cardiac injury.

Language: Английский

Citations

11
MnSOD non-acetylation mimic knock-in mice exhibit dilated cardiomyopathy DOI Creative Commons
Joseph Schell, Sung‐Jen Wei, Jilei Zhang

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 229, P. 58 - 67

Published: Jan. 15, 2025

Language: Английский

Citations

0
Regulatory mechanisms of m6A methylation in dilated cardiomyopathy DOI
Hao Zhang, Haiyang Guo,

Fengjiao Han

et al.

American Journal of Translational Research, Journal Year: 2025, Volume and Issue: 17(1), P. 47 - 59

Published: Jan. 1, 2025

Dilated cardiomyopathy (DCM) is a complex heart condition marked by genetic mutations, myocardial dysfunction, and progressive failure. N6-methyladenosine (m6A) methylation, key epigenetic modification, plays crucial role in DCM regulating gene expression various pathologic processes, including cardiomyocyte death, inflammation, fibrosis, mitochondrial dysfunction. m6A modifications influence survival modulating apoptosis, necroptosis, ferroptosis, autophagy-related genes, balancing cellular death pathways. Additionally, m6A-driven regulation of inflammation fibrosis contributes to immune microenvironment stability extracellular matrix remodeling, affecting fibroblast activation stiffness. Mitochondrial health, vital for energy demands, also regulated methylation. Enzymes like methyltransferase-like (METTL) 3 METTL14 promote mitophagy-related expression, while fat mass obesity-associated protein modulates calcium homeostasis, mitigating oxidative stress imbalances. Targeting m6A-related enzymes with small molecules, editing, or RNA interference (RNAi) offers potential tailored therapy. Emerging technologies, such as nanopore m6A-modified mRNA detection, reveal new insight into metabolism, suggesting novel therapeutic avenues. This review underscores methylation pivotal mechanism DCM, providing basis advanced diagnosis

Language: Английский

Citations

0
Irisin Mitigates Doxorubicin-Induced Cardiotoxicity by Reducing Oxidative Stress and Inflammation via Modulation of the PERK-eIF2α-ATF4 Pathway DOI Creative Commons
Zilong Zhang,

Xiaolin Yu,

Jie Li

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1067 - 1081

Published: Feb. 1, 2025

Doxorubicin (DOX), an anthracycline antibiotic, has limited clinical use due to its pronounced cardiotoxicity. Irisin, a myokine known for metabolic regulation, shown therapeutic effects on cardiovascular disease. This study investigates the potential cardioprotective function of irisin in reducing cardiac injury induced by DOX. In vitro, H9c2 cells were pretreated with (20 nM) 24 hours before exposure DOX (1 μM). vivo, C57BL/6 mice administered (5 mg/kg/week, i.p.) 4 weeks, reaching cumulative dose 20 mg/kg. Irisin mg/kg/ 3 days, was both 7 days prior and during injection.Cardiac evaluated echocardiography, histology assessed using HE, WGA, Masson staining. Myocardial markers quantified ELISA, apoptosis analyzed via TUNEL Oxidative stress determined measuring antioxidase activity, MDA GSH levels, DHE staining, while mitochondrial superoxide production MitoSOX Red. Mitochondrial morphology transmission electron microscopy Seahorse analysis, respectively Inflammatory cytokines serum cell supernatants. The role PERK-eIF2α-ATF4 pathway mediated investigated Western blot. Using adeno-associated virus serotype-9 carrying mouse FNDC5 shRNA (AAV9-shFNDC5) further validated protective DOX-induced myocardial injury. reduced dysfunction fibrosis. Moreover, mitigated oxidative inflammation through inhibiting activated DOX, thus preserving function. While knockdown exacerbated heart activation, which partially reversed irisin. mitigates modulating pathway, highlighting as prospective approach combating

Language: Английский

Citations

0
NAD_MCNN: Combining Protein Language Models and Multiwindow Convolutional Neural Networks for Deacetylase NAD+ Binding Site Prediction DOI
Van‐The Le, Yuchen Liu,

Yan‐Yun Chang

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(4)

Published: April 1, 2025

Sirtuins, a class of NAD+ -dependent deacetylases, play key role in aging, metabolism, and longevity. Their interaction with at the catalytic site is crucial for function, but experimental methods to map binding sites are time consuming. To address this, we developed computational method integrating pretrained protein language models multiwindow convolutional neural networks (CNNs). This captures sequence information diverse local patterns, achieving state-of-the-art performance, AUC 0.9733 human sirtuin proteins 0.9701 other NAD-dependent deacylation enzymes. These findings offer insights into sirtuins aging their broader biological functions while providing new path identifying therapeutic targets aging-related diseases.

Language: Английский

Citations

0