Identification of methylation signatures and rules for predicting the severity of SARS-CoV-2 infection with machine learning methods DOI Creative Commons
Zhiyang Liu, Mei Meng, Shi‐Jian Ding

et al.

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

Published: Sept. 23, 2022

Patients infected with SARS-CoV-2 at various severities have different clinical manifestations and treatments. Mild or moderate patients usually recover conventional medical treatment, but severe require prompt professional treatment. Thus, stratifying for targeted treatment is meaningful. A computational workflow was designed in this study to identify key blood methylation features rules that can distinguish the severity of infection. First, expression profile were deeply analyzed by a Monte Carlo feature selection method. list generated. Next, ranked fed into incremental method determine optimal classification algorithms, thereby further building classifiers. These selected functional enrichment detect their biofunctional information. Furthermore, set up white-box algorithm, decision tree, uncover patterns on Some genes (PARP9, MX1, IRF7), corresponding essential sites, validated published academic literature. Overall, contributes revealing potential provides reference patient stratification. The physicians prioritize allocate health resources COVID-19 based predicted outcomes.

Language: Английский

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives DOI Creative Commons
Oskar Ciesielski,

Marta Biesiekierska,

Baptiste Panthu

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(2)

Published: Jan. 25, 2022

Abstract Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering structure and functions proteins. The action most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination glycosylation is well documented. A less explored protein PTM, conversion peptidylarginine to citrulline, subject this review. process citrullination catalysed by deiminases (PADs), family conserved enzymes expressed in variety human tissues. Accumulating evidence suggest that plays significant role regulating cellular gene expression affecting multitude pathways modulating chromatin status. Here, we will discuss biochemical nature arginine citrullination, enzymatic machinery behind it also provide information on pathological consequences development inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis COVID-19), cancer thromboembolism. Finally, developments inhibitors against recent clinical trials providing promising therapeutic approach disease targeting are discussed.

Language: Английский

Citations

96
Role of Histone Post-Translational Modifications in Inflammatory Diseases DOI Creative Commons
Yingying Lin, Ting Qiu, Guifeng Wei

et al.

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

Published: Feb. 24, 2022

Inflammation is a defensive reaction for external stimuli to the human body and generally accompanied by immune responses, which associated with multiple diseases such as atherosclerosis, type 2 diabetes, Alzheimer’s disease, psoriasis, asthma, chronic lung diseases, inflammatory bowel virus-associated diseases. Epigenetic mechanisms have been demonstrated play key role in regulation of inflammation. Common epigenetic regulations are DNA methylation, histone modifications, non-coding RNA expression; among these, modifications embrace various post-modifications including acetylation, phosphorylation, ubiquitination, ADP ribosylation. This review focuses on significant progression providing potential target clinical therapy inflammation-associated

Language: Английский

Citations

55
Long-term outcomes of hospitalized patients with SARS-CoV-2/COVID-19 with and without neurological involvement: 3-year follow-up assessment DOI Creative Commons

Anna Eligulashvili,

Moshe Gordon,

Jimmy S. Lee

et al.

PLoS Medicine, Journal Year: 2024, Volume and Issue: 21(4), P. e1004263 - e1004263

Published: April 4, 2024

Background Acute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes patients with and without significant manifestations during initial COVID-19 hospitalization. Methods findings Patients hospitalized for Severe Respiratory Syndrome 2 (SARS-CoV-2) infection between 03/01/2020 4/16/2020 in Montefiore Health System Bronx, an epicenter early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). consisted 414 1,199 propensity-matched (for age severity score) manifestations. Neurological involvement phase included stroke, new or recrudescent seizures, anatomic brain lesions, presence altered mentation evidence impaired cognition arousal, neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, skeletal muscle injury normal orientation arousal signs). There no group differences female sex composition (44.93% versus 48.21%, p = 0.249), ICU IMV status, white, not Hispanic (6.52% 7.84%, 0.380), (33.57% 38.20%, 0.093), except black non-Hispanic (42.51% 36.03%, 0.019). Primary mortality, heart attack, major adverse cardiovascular events (MACE), reinfection, hospital readmission post-discharge. Secondary neuroimaging (hemorrhage, active prior mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), volume loss). More discharged rehabilitation (10.39% 3.34%, < 0.001) skilled nursing facilities (35.75% 25.35%, fewer home (50.24% 66.64%, than matched controls. Incidence any reason (65.70% 60.72%, 0.036), stroke (6.28% 2.34%, 0.001), MACE (20.53% 16.51%, 0.032) higher Per Kaplan–Meier univariate survival curve analysis, such more likely die post-discharge compared controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; 0.001)). Across both cohorts, causes death (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza pneumonia (13.79%, 9.89%), (10.34%, 7.69%), respiratory distress syndrome (ARDS) 6.59%). Factors associated mortality after leaving involved (odds ratio (OR): 1.802 CI [1.237, 2.608]; 0.002)), discharge disposition (OR: 1.508 [1.276, 1.775]; 0.001)), congestive failure 2.281 [1.429, 3.593]; score 1.177 [1.062, 1.304]; older 1.027 [1.010, 1.044]; 0.002)). radiological findings, that showed significantly age-adjusted loss ( 0.045) The study’s patient limited infected first wave when hospitals overburdened, vaccines yet available, treatments limited. Patient profiles might differ interrogating subsequent waves. Conclusions had worse long-term These raise awareness need closer monitoring timely interventions manifestations, as their course involving enhanced morbidity mortality.

Language: Английский

Citations

12
Epigenomics in COVID-19; the Link Between DNA Methylation, Histone Modifications and SARS-CoV-2 Infection DOI Creative Commons
Milad Shirvaliloo

Epigenomics, Journal Year: 2021, Volume and Issue: 13(10), P. 745 - 750

Published: April 20, 2021

Language: Английский

Citations

29
Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity DOI Open Access
Ata Mahmoodpoor, Sarvin Sanaie, Faranak Roudbari

et al.

Gene, Journal Year: 2021, Volume and Issue: 811, P. 146069 - 146069

Published: Nov. 27, 2021

Language: Английский

Citations

29
SARS-CoV-2 and the Nucleus DOI Creative Commons
Mengqi Chen, Yue Ma, Wakam Chang

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(12), P. 4731 - 4743

Published: Jan. 1, 2022

The ongoing COVID-19 pandemic is caused by an RNA virus, SARS-CoV-2.The genome of SARS-CoV-2 lacks a nuclear phase in its life cycle and replicated the cytoplasm.However, interfering with trafficking using pharmacological inhibitors greatly reduces virus infection replication other coronaviruses blocked enucleated cells, suggesting critical role nucleus infection.Here, we summarize alternations pathways SARS-CoV-2, including translocation pathways, innate immune responses, mRNA metabolism, epigenetic mechanisms, DNA damage response, cytoskeleton regulation, rupture.We consider how these contribute to discuss therapeutic treatments that target focusing on small molecule drugs are being used clinical studies.

Language: Английский

Citations

21
Epigenetic Regulation of the Renin–Angiotensin–Aldosterone System in Hypertension DOI Open Access
Yoshimichi Takeda, Masashi Demura, Takashi Yoneda

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8099 - 8099

Published: July 25, 2024

Activation of the renin–angiotensin–aldosterone system (RAAS) plays an important pathophysiological role in hypertension. Increased mRNA levels angiotensinogen angiotensin-converting enzyme, angiotensin type 1 receptor gene, Agtr1a, and aldosterone synthase CYP11B2, have been reported heart, blood vessels, kidneys salt-sensitive However, mechanism gene regulation each component RAAS cardiovascular renal tissues is unclear. Epigenetic mechanisms, which are for regulating expression, include DNA methylation, histone post-translational modifications, microRNA (miRNA) regulation. A close association exists between low methylation at CEBP-binding sites increased AGT expression visceral adipose tissue heart hypertensive rats. Several miRNAs influence associated with diseases. Expression both ACE ACE2 genes regulated by miRNAs. CYP11B2 reversibly epigenetic modifications related to The mineralocorticoid (MR) tissues, many contribute pathogenesis 11beta-hydroxysteroid dehydrogenase 2 (HSD11B2) also vascular HSD11B2 pathogenetic

Language: Английский

Citations

4
Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19 DOI Creative Commons
Benjamin L. Spector, Boryana Koseva, Rebecca McLennan

et al.

BMC Medical Genomics, Journal Year: 2025, Volume and Issue: 18(1)

Published: April 1, 2025

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied presentations from asymptomatic to death. Efforts identify factors responsible for differential COVID-19 severity include but are not limited genome wide association studies (GWAS) and transcriptomic analysis. More recently, variability in host epigenomic profiles have garnered attention, providing links severity. However, whole epigenome analysis of the tract, target tissue SARS-CoV-2, remains ill-defined. We interrogated nasal methylome pathophysiologic drivers through bisulfite sequencing (WGBS) samples positive individuals with mild presentation disease. noted DNA methylation intergenic regions low methylated (LMRs), demonstrating importance distal regulatory elements gene regulation illness. Additionally, we demonstrated pathways implicated immune cell recruitment function, inflammatory response. found significant hypermethylation FUT4 promoter implicating impaired neutrophil adhesion also identified ELF5 binding sites suggesting downregulation targets cavity as a factor phenotypic variability. This study marker response SARS-CoV-2 infection, enhancer-like playing roles. It is difficult discern whether this predisposing COVID-19, or if differences occur These may contribute severity, conversely, system respond infection

Language: Английский

Citations

0
Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs DOI Open Access
Suvasmita Rath, Venkateswarlu Perikala, Atala Bihari Jena

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 143, P. 112095 - 112095

Published: Aug. 30, 2021

Angiotensin-converting enzyme-2 (ACE2) is one of the major components renin-angiotensin system (RAS) and participates in physiological functions cardiovascular lungs. Recent studies identified ACE2 as receptor for S-protein novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) thus acts gateway viral entry into human body. Virus infection causes an imbalance RAS axis induces lungs injury fibrosis. Various factors regulate expression patterns well control its epigenetic status at both transcription translational levels. This review mainly focused on impact environmental toxicants, drugs, endocrine disruptors, hypoxia controlling parameters possible modulation by changes which are marked DNA methylation, histone modifications, micro-RNAs (miRNAs) profile. Furthermore, we have emphasized interventions various phytochemicals bioactive compounds epidrugs that ACE2-S-protein interaction thereby curb infection. Since important component RAAS a crucial point SARS-CoV-2, dynamics response to extrinsic intrinsic contemporary relevance. We collated updated information modulated epidrugs, urge take over further these regulators unravel many more systemic linkages related metabolic infectious diseases, general SARS-CoV-2 particular development targeted interventions.

Language: Английский

Citations

21
Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings DOI Creative Commons
Larissa Marcely Gomes Cassiano,

Vanessa Cavalcante‐Silva,

Marina da Silva Oliveira

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 13, 2023

COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe patients were used to assess the potential of as adjuvant drug. The normalized expression a panel still dysregulated leukocytes despite glucocorticoid therapy during hospitalization. also increased flux sulfur amino acid pathway, regulates bioavailability methyl. Accordingly, B12-induced downregulation CCL3 strongly negatively correlated with hypermethylation CpGs its regulatory regions. Transcriptome analysis revealed attenuates effects on most inflammation-related pathways affected by disease. As far we are aware, is first study demonstrate pharmacological modulation markings favorably central components physiopathology.

Language: Английский

Citations

9