Building an Adverse Outcome Pathway network for COVID-19 DOI Creative Commons
Penny Nymark, Laure‐Alix Clerbaux, Maria João Amorim

et al.

Frontiers in Systems Biology, Journal Year: 2024, Volume and Issue: 4

Published: June 7, 2024

The COVID-19 pandemic generated large amounts of data on the disease pathogenesis leading to a need for organizing vast knowledge in succinct manner. Between April 2020 and February 2023, CIAO consortium exploited Adverse Outcome Pathway (AOP) framework comprehensively gather systematically organize published scientific literature pathology. project considered 24 pathways relevant by identifying essential key events (KEs) 19 adverse outcomes observed patients. While an individual AOP defines causally linked perturbed KEs towards outcome, building network visually reflect interrelatedness various outcomes. In this study, 17 those AOPs were selected based quality criteria computationally derive network. This primary highlighted consider tissue specificity helped identify missing or redundant elements which then manually implemented final Such enabled visualization complex interactions multifaceted confirmed central role inflammatory response disease. addition, study disclosed importance terminology harmonization tissue/organ building. Furthermore unequal completeness information contained tighter implementation FAIR principles improve findability, accessibility, interoperability re-usability. Finally, underlined that describing specific SARS-CoV-2 replication discriminating physiological from pathological inflammation is necessary but requires adaptations framework. Hence, challenges encountered, we proposed recommendations ongoing future AOP-aligned consortia aiming build biologically meaningful networks context of, not limited to, viral diseases.

Language: Английский

COVID-19 annual update: a narrative review DOI Creative Commons
Michela Biancolella, Vito Luigi Colona, Lucio Luzzatto

et al.

Human Genomics, Journal Year: 2023, Volume and Issue: 17(1)

Published: July 24, 2023

Abstract Three and a half years after the pandemic outbreak, now that WHO has formally declared emergency is over, COVID-19 still significant global issue. Here, we focus on recent developments in genetic genomic research COVID-19, give an outlook state-of-the-art therapeutical approaches, as gradually transitioning to endemic situation. The sequencing characterization of rare alleles different populations made it possible identify numerous genes affect either susceptibility or severity disease. These findings provide beginning new avenues pan-ethnic therapeutic well potential screening protocols. causative virus, SARS-CoV-2, spotlight, but novel threatening virus could appear anywhere at any time. Therefore, continued vigilance further warranted. We also note emphatically prevent future pandemics other world-wide health crises, imperative capitalize what have learnt from COVID-19: specifically, regarding its origins, world’s response, insufficient preparedness. This requires unprecedented international collaboration timely data sharing for coordination effective response rapid implementation containment measures.

Language: Английский

Citations

28

A pragmatic framework for the application of new approach methodologies in one health toxicological risk assessment DOI Creative Commons
Kelly A. Magurany, Xiaoqing Chang,

Rebecca A. Clewell

et al.

Toxicological Sciences, Journal Year: 2023, Volume and Issue: 192(2), P. 155 - 177

Published: Feb. 14, 2023

Globally, industries and regulatory authorities are faced with an urgent need to assess the potential adverse effects of chemicals more efficiently by embracing new approach methodologies (NAMs). NAMs include cell tissue methods (in vitro), structure-based/toxicokinetic models silico), that toxicant interactions biological macromolecules chemico), alternative models. Increasing knowledge on chemical toxicokinetics (what body does chemicals) toxicodynamics do body) obtained from in silico vitro systems continues provide opportunities for modernizing risk assessments. However, directly leveraging data derivation human health-based reference values has not received acceptance due uncertainties extrapolating NAM results populations, including metabolism, complex pathways, multiple exposures, interindividual susceptibility vulnerable populations. The objective this article is a standardized pragmatic framework applies integrated approaches focus quantitative vivo extrapolation (QIVIVE) extrapolate cellular exposures equivalent doses which can be derived. proposed intends systematically account complexities interpretation support sound health safety decisions diverse industrial sectors (food systems, cosmetics, chemicals, pharmaceuticals etc.). Case studies entities, using existing data, presented demonstrate utility while highlighting sources population bias uncertainty, importance Good Method Reporting Practices.

Language: Английский

Citations

25

Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways DOI Open Access
Laure‐Alix Clerbaux, Julija Filipovska, Amalia Muñoz

et al.

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(18), P. 5400 - 5400

Published: Sept. 14, 2022

Alteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to dysbiosis as an adverse outcome following SARS-CoV-2 presence gastrointestinal tract. Evidence from literature and current uncertainties are reported for each step of different pathways. One pathway investigates evidence that intestinal infection by inducing inflammation alters microbiota. Another links binding viral S protein angiotensin-converting enzyme 2 (ACE2) dysregulation this receptor, essential homeostasis—notably amino acid metabolism—leading dysbiosis. Additionally, could induce infecting bacteria. Assessing within Adverse Outcome Pathway framework justifies confidence proposed support disease management permits identification inconsistencies knowledge gaps orient further research.

Language: Английский

Citations

31

A curated gene and biological system annotation of adverse outcome pathways related to human health DOI Creative Commons
Laura Aliisa Saarimäki, Michele Fratello, Alisa Pavel

et al.

Scientific Data, Journal Year: 2023, Volume and Issue: 10(1)

Published: June 24, 2023

Adverse outcome pathways (AOPs) are emerging as a central framework in modern toxicology and other fields biomedicine. They serve an extension of pathway-based concepts by depicting biological mechanisms causally linked sequences key events (KEs) from molecular initiating event (MIE) to adverse outcome. AOPs guide the use development new approach methodologies (NAMs) aimed at reducing animal experimentation. While model systemic various levels organisation, toxicogenomics provides means study chemical exposures. Systematic integration these two would improve application AOP-based knowledge while also supporting interpretation complex omics data. Hence, we established this link through rigorous curation annotations for KEs human relevant AOPs. We further expanded consolidated context KEs. These curated pave way embed data interpretation, facilitating emergence

Language: Английский

Citations

14

Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona DOI Creative Commons
Miquel Porta, José Pumarega, Magda Gasull

et al.

Environmental Research, Journal Year: 2023, Volume and Issue: 223, P. 115419 - 115419

Published: Feb. 4, 2023

There is wide, largely unexplained heterogeneity in immunological and clinical responses to SARS-CoV-2 infection. Numerous environmental chemicals, such as persistent organic pollutants (POPs) chemical elements (including some metals, essential trace elements, rare earth minority elements), are immunomodulatory cause a range of adverse events. no prospective studies on the effects substances incidence infection COVID-19.To investigate influence blood concentrations POPs measured several years before pandemic development COVID-19 individuals from general population.We conducted cohort study 154 population Barcelona. were samples collected 2016-2017. was detected by rRT-PCR nasopharyngeal swabs and/or antibody serology using eighteen isotype-antigen combinations 2020-2021. We analyzed associations between contaminants COVID-19, taking into account personal habits living conditions during pandemic.Several historically prevalent POPs, well arsenic, cadmium, mercury, zinc, not associated with nor However, DDE (adjusted OR = 5.0 [95% CI: 1.2-21]), lead (3.9 [1.0-15]), thallium (3.4 [1.0-11]), ruthenium (5.0 [1.8-14]) tantalum, benzo(b)fluoranthene, DDD, manganese. Thallium (3.8 [1.6-8.9]), (2.9 [1.3-6.7]) infection, so lead, gold, (protectively) iron selenium. identified mixtures up five groups, all independently outcomes.Our results provide first population-based evidence an association individual may contribute explain population. If confirmed causal, means available mitigate corresponding risks.

Language: Английский

Citations

12

Peculiar weather patterns effects on air pollution and COVID-19 spread in Tokyo metropolis DOI Creative Commons
Maria A. Zoran, Roxana Savastru, Dan Savastru

et al.

Environmental Research, Journal Year: 2023, Volume and Issue: 228, P. 115907 - 115907

Published: April 18, 2023

As a pandemic hotspot in Japan, between March 1, 2020–October 2022, Tokyo metropolis experienced seven COVID-19 waves. Motivated by the high rate of incidence and mortality during seventh wave, environmental/health challenges we conducted time-series analysis to investigate long-term interaction air quality climate variability with viral Tokyo. Through daily time series geospatial observational pollution/climate data, death cases, this study compared environmental conditions multiwaves. In spite five State Emergency (SOEs) restrictions associated pandemic, (2020–2022) period recorded low improvements relative (2015–2019) average annual values, namely: Aerosol Optical Depth increased 9.13% 2020 year, declined 6.64% 2021, 12.03% 2022; particulate matter PM2.5 PM10 decreased 2020, 2022 years 10.22%, 62.26%, 0.39%, respectively 4.42%, 3.95%, 5.76%. For (2021–2022) ratio PM2.5/PM10 was (0.319 ± 0.1640), showing higher contribution aerosol loading traffic-related coarse particles comparison fine particles. The highest rates cases wave (1 July 2022–1 October 2022) may be attributed accumulation near ground levels pollutants pathogens due to: 1) peculiar persistent atmospheric anticyclonic circulation strong positive anomalies geopotential height at 500 hPa; 2) lower Planetary Boundary Layer (PBL) heights; 3) maximum temperature land surface prolonged heat waves (HWs) summer 4) no imposed restrictions. Such findings can guide public decision-makers design proper strategies curb pandemics under stable weather HWs large metropolitan areas.

Language: Английский

Citations

12

Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19 DOI Open Access
Laure‐Alix Clerbaux, Sally A. Mayasich, Amalia Muñoz

et al.

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(19), P. 5691 - 5691

Published: Sept. 26, 2022

The gut has been proposed as a potential alternative entry route for SARS-CoV-2. This was mainly based on the high levels of SARS-CoV-2 receptor expressed in gastrointestinal (GI) tract, observations GI disorders (such diarrhea) some COVID-19 patients and detection RNA feces. However, underlying mechanisms remain poorly understood. It that can productively infect enterocytes, damaging intestinal barrier contributing to inflammatory response, which might lead manifestations, including diarrhea. Here, we report methodological approach assess evidence supporting sequence events driving enteric infection up adverse outcomes. Exploring permits highlight knowledge gaps current inconsistencies literature guide further research. Based insights transmission, then discuss implication clinical practice, long COVID. A better understanding is still needed improve disease management could help identify innovative therapies or preventive actions targeting tract.

Language: Английский

Citations

19

Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework DOI Creative Commons
Muhammad Ali Shahbaz, F Bernardi, Arto Alatalo

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(19), P. 3027 - 3027

Published: Sept. 27, 2022

Loss of the sense smell (anosmia) has been included as a COVID-19 symptom by World Health Organization. The majority patients recover within few weeks postinfection (short-term anosmia), while others report persistent anosmia. Several studies have investigated mechanisms leading to anosmia in COVID-19; however, evidence is scattered, and remain poorly understood. Based on comprehensive review literature, we aim here evaluate current knowledge uncertainties regarding short-term following SARS-CoV-2 infection. We applied an adverse outcome pathway (AOP) framework, well established toxicology, propose sequence measurable key events (KEs) COVID-19. Those KEs are (1) Spike proteins binding ACE-2 expressed sustentacular (SUS) cells olfactory epithelium (OE); (2) viral entry into SUS cells; (3) replication (4) cell death; (5) damage sensory neurons (OE). This AOP-aligned approach allows for identification gaps where more research should be conducted therapeutic intervention could act. Finally, this AOP gives frame explain several disease features can linked specific factors that lead interindividual differences response

Language: Английский

Citations

18

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022 DOI Open Access

Nikita Narayan Naik,

Bharadwaja Vadloori,

Suresh Poosala

et al.

Alternatives to Laboratory Animals, Journal Year: 2023, Volume and Issue: 51(4), P. 263 - 288

Published: June 6, 2023

Animal experimentation has been integral to drug discovery and development safety assessment for many years, since it provides insights into the mechanisms of efficacy toxicity (e.g. pharmacology, pharmacokinetics pharmacodynamics). However, due species differences in physiology, metabolism sensitivity drugs, animal models can often fail replicate effects drugs chemicals human patients, workers consumers. Researchers across globe are increasingly applying Three Rs principles by employing innovative methods research testing. The concept focuses on: replacement with vitro silico or studies), on reduction number animals required achieve objectives, refinement existing experimental practices eliminating distress enhancing wellbeing). For last two Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, organised an annual International Conference 3Rs Research Progress. This series global conferences aims bring together researchers diverse expertise interests, platform where they share discuss their promote according principles. In November 2022, 3rd international conference, Advances Models Cutting-Edge Alternatives, took place at GITAM University Vishakhapatnam (AP, India) hybrid format (i.e. online in-person). These conference proceedings provide details presentations, which were categorised under five different topic sessions. It also describes special interactive session strategies preclinical oncology, was held end first day.

Language: Английский

Citations

10

Introduction to Multiscale Modeling for One Health Approaches DOI
Laura Aliisa Saarimäki, Giusy del Giudice, Marcella Torres Maia

et al.

Challenges and advances in computational chemistry and physics, Journal Year: 2025, Volume and Issue: unknown, P. 199 - 220

Published: Jan. 1, 2025

Language: Английский

Citations

0