Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination DOI Creative Commons
Alina P.S. Pang, Albert Higgins‐Chen, Florence Comite

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: June 3, 2022

The host epigenetic landscape rapidly changes during SARS-CoV-2 infection, and evidence suggest that severe COVID-19 is associated with durable scars to the epigenome. Specifically, aberrant DNA methylation in immune cells alterations clocks blood relate COVID-19. However, a longitudinal assessment of states from healthy individuals prior following test-confirmed non-hospitalized has not been performed. Moreover, impact mRNA vaccines upon epigenome remains understudied. Here, we first examined 21 participants diagnosis at median time frame 8.35 weeks; 756 CpGs were identified as differentially methylated an FDR adjusted p -value < 0.05. These enriched gene body, northern southern shelf regions genes involved metabolic pathways. Integrative analysis revealed overlap among transcriptional infection datasets. Principal component-based clock estimates PhenoAge GrimAge significantly increased people over 50 by average 2.1 0.84 years. In contrast, PCPhenoAge decreased fewer than 2.06 This observed divergence was related age cell-type compositional CD4 + T cells, B granulocytes, plasmablasts, exhausted naïve cells. Complementary analyses 36 Pfizer Moderna mRNA-based vaccination reduced principal Horvath 3.91 years for those who received Moderna. reduction chronological plasmablasts pre- post-vaccination. findings potential utility biomarker vaccine responses. Future research will need unravel significance durability short-term exposure vaccination.

Language: Английский

Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19 DOI Creative Commons
Bibo Zhu, Xiaoqin Wei, Harish Narasimhan

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(82)

Published: Feb. 23, 2023

The relationship between diabetes and coronavirus disease 2019 (COVID-19) is bidirectional: Although individuals with high blood glucose (hyperglycemia) are predisposed to severe COVID-19, acute respiratory syndrome 2 (SARS-CoV-2) infection can also cause hyperglycemia exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network SARS-CoV-2 infection, hyperglycemia, hyperinflammation, all factors that drive COVID-19 pathophysiology, urgently needed. Here, we show genetic ablation or pharmacological inhibition mitochondrial pyruvate carrier (MPC) attenuates after influenza pneumonia. MPC using a second-generation insulin sensitizer, MSDC-0602K (MSDC), dampened pulmonary inflammation promoted lung recovery while concurrently reducing levels hyperlipidemia viral pneumonia in obese mice. Mechanistically, enhanced fitness destabilized hypoxia-inducible factor-1α, leading virus-induced inflammatory responses both murine human macrophages. We further showed MSDC nirmatrelvir (the antiviral component Paxlovid) provide protection against host development suppressed cellular autopsies, demonstrating its translational potential for treating COVID-19. Collectively, uncover pathway simultaneously modulates inflammation, tissue recovery, health, presenting synergistic therapeutic strategy treat particularly patients disease.

Language: Английский

Citations

24
Signaling pathways and intervention for therapy of type 2 diabetes mellitus DOI Creative Commons
Rong Cao,

Huimin Tian,

Yu Zhang

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: June 1, 2023

Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for broad range comorbidities, including vascular, visual, neurological, kidney, liver diseases. Moreover, recent data suggest mutual interplay between T2DM Corona Virus Disease 2019 (COVID-19). characterized by insulin resistance (IR) pancreatic β cell dysfunction. Pioneering discoveries throughout past few decades have established notable links signaling pathways pathogenesis therapy. Importantly, number substantially control advancement core pathological changes in T2DM, IR dysfunction, as well additional pathogenic disturbances. Accordingly, an improved understanding these sheds light on tractable targets strategies developing repurposing critical therapies to treat its complications. In this review, we provide brief overview history pathways, offer systematic update role mechanism key underlying onset, development, progression T2DM. content, also summarize current therapeutic drugs/agents associated with treatment complications, discuss some implications directions future field.

Language: Английский

Citations

24
Infection with SARS-CoV-2 can cause pancreatic impairment DOI Creative Commons
Wei Deng, Linlin Bao, Zhiqi Song

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 12, 2024

Abstract Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction an even higher risk of the occurrence diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models 121 vaccinated NHPs 2020 to 2023 patients. Multi-label immunofluorescence revealed direct infection both exocrine endocrine cells by virus humans. Minor limited phenotypic histopathological changes were observed adult models. Systemic proteomics metabolomics results indicated metabolic disorders, mainly enriched insulin resistance pathways, NHPs, along with elevated fasting C-peptide C-peptide/glucose ratio levels. Furthermore, elder causes loss beta (β) lower expressed-insulin situ characterized islet amyloidosis necrosis, activation α-SMA aggravated fibrosis consisting collagen serum, increase inflammation stress markers, ICAM-1 G3BP1, more severe dysfunction. In contrast, vaccination maintained glucose homeostasis activating receptor α β. Overall, cumulative diabetes post-COVID-19 is closely tied age, suggesting attention should be paid blood sugar management elderly

Language: Английский

Citations

9
Adult Long Coronavirus Disease 2019 DOI
Ivette F. Emery, Clifford J. Rosen

Infectious Disease Clinics of North America, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination DOI Creative Commons
Alina P.S. Pang, Albert Higgins‐Chen, Florence Comite

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: June 3, 2022

The host epigenetic landscape rapidly changes during SARS-CoV-2 infection, and evidence suggest that severe COVID-19 is associated with durable scars to the epigenome. Specifically, aberrant DNA methylation in immune cells alterations clocks blood relate COVID-19. However, a longitudinal assessment of states from healthy individuals prior following test-confirmed non-hospitalized has not been performed. Moreover, impact mRNA vaccines upon epigenome remains understudied. Here, we first examined 21 participants diagnosis at median time frame 8.35 weeks; 756 CpGs were identified as differentially methylated an FDR adjusted p -value < 0.05. These enriched gene body, northern southern shelf regions genes involved metabolic pathways. Integrative analysis revealed overlap among transcriptional infection datasets. Principal component-based clock estimates PhenoAge GrimAge significantly increased people over 50 by average 2.1 0.84 years. In contrast, PCPhenoAge decreased fewer than 2.06 This observed divergence was related age cell-type compositional CD4 + T cells, B granulocytes, plasmablasts, exhausted naïve cells. Complementary analyses 36 Pfizer Moderna mRNA-based vaccination reduced principal Horvath 3.91 years for those who received Moderna. reduction chronological plasmablasts pre- post-vaccination. findings potential utility biomarker vaccine responses. Future research will need unravel significance durability short-term exposure vaccination.

Language: Английский

Citations

35