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

The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis DOI Creative Commons
Farzaneh Fakharian,

Siva Thirugnanam,

David A. Welsh

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 11(7), P. 1849 - 1849

Published: July 21, 2023

The gut microbiome plays a critical role in maintaining overall health and immune function. However, dysbiosis, an imbalance composition, can have profound effects on various aspects of human health, including susceptibility to viral infections. Despite numerous studies investigating the influence infections microbiome, impact dysbiosis infection pathogenesis remains relatively understudied. clinical variability observed SARS-CoV-2 seasonal influenza infections, presence natural HIV suppressors, suggests that host-intrinsic factors, may contribute pathogenesis. has been shown host system by regulating intestinal homeostasis through interactions with cells. This review aims enhance our understanding how perturb mucosal cells, affecting response Specifically, we focus exploring between gamma delta (γδ) T cells microbes context inflammatory examine highlighting disease outcomes. Furthermore, discuss emerging evidence potential future directions for modulation therapy

Language: Английский

Citations

41

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID DOI Creative Commons
A. Satyanarayan Naidu, Chin‐Kun Wang, Pingfan Rao

et al.

npj Science of Food, Journal Year: 2024, Volume and Issue: 8(1)

Published: March 30, 2024

Language: Английский

Citations

8

The Contribution of Diet Therapy and Probiotics in the Treatment of Sarcopenia Induced by Prolonged Immobilization Caused by the COVID-19 Pandemic DOI Open Access
Carmen Delia Nistor-Cseppento,

Titus David Moga,

Alexa Florina Bungău

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(21), P. 4701 - 4701

Published: Nov. 7, 2022

The prolonged immobilization associated with COVID-19 infection and the restrictions imposed by pandemic have determined major changes in physical activity eating habits, a negative impact on performance. This study monitored non-pharmacological interventions (diet therapy probiotics) managing sarcopenia for patients recent SARS-CoV-2 history (14 days). A prospective was performed 200 (between December 2020–December 2021), SPPB score < 9, randomly divided into: Group K—DP (93 patients) dietary (protein 1.2–1.5 g/kg) probiotics two months; K—non-DP (107 without diet probiotics. All were included specific training program (40 min), three sessions per week. Skeletal muscle index (SMI), serum albumin, hemoglobin determined. SMI initially low both groups significant statistical differences (6.5 ± 0.52 kg/m2 vs. 6.7 0.57 Kg/m2 K—DP, p = 0.135). After months, difference between initial final values (6.92 0.50 6.77 0.56 kg/m2, 0.048). In at end of study, more normal (n 32 → N 70) (p 0.001) fewer 0.001). albumin means (Group K—non-DP, 4.17 1.04 g/dL, 3.95 0.98 g/dL) not statistically significantly different 0.122). level improved following hyper protein enriched pro-biotics 0.003). Diet therapy, consisting increased intake demonstrated superiority improving functional status infection.

Language: Английский

Citations

31

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

Streptococcus salivarius and Ligilactobacillus salivarius: Paragons of Probiotic Potential and Reservoirs of Novel Antimicrobials DOI Creative Commons
McKinley Williams, Leif Smith

Microorganisms, Journal Year: 2025, Volume and Issue: 13(3), P. 555 - 555

Published: Feb. 28, 2025

This review highlights several basic problems associated with bacterial drug resistance, including the decreasing efficacy of commercially available antimicrobials as well related problem microbiome irregularity and dysbiosis. The article explains that this present situation is addressable through LAB species, such Streptococcus salivarius Ligilactobacillus salivarius, which are established synthesizers both broad- narrow-spectrum antimicrobials. sheer number produced by species breadth their biological effects, in terms bacteriostatic/bactericidal abilities immunomodulation, make them prime candidates for new probiotics antibiotics. Given ease molecules can be biochemically engineered fact many these compounds target evolutionarily constrained sites, it seems apparent producing organisms ought to looked at next generation robust dual action symbiotic drugs.

Language: Английский

Citations

0

Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19 DOI Creative Commons
Joon‐Ki Chung, Julia Pierce, Craig L. Franklin

et al.

Disease Models & Mechanisms, Journal Year: 2025, Volume and Issue: 18(9)

Published: April 8, 2025

ABSTRACT Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 deaths, it has become evident that COVID-19 is not solely pulmonary disease. Emerging evidence shown that, subset patients, certain symptoms − including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain – all indicate role vascular, neurological gastrointestinal (GI) pathology disease process. Many these processes persist long after been resolved, ‘long COVID’ or post-acute sequelae (PASC). The molecular mechanisms underlying systemic conditions associated remain incompletely defined. Appropriate animal models provide method understanding at system level through study progression, tissue pathology, immune response to pathogen behavioral responses. However, very few studies have addressed PASC whether existing hold promise for studying this challenging problem. Here, we review current literature on cardiovascular, GI pathobiology caused by along established manifestations their prospects use studies. Our aim guidance selection appropriate order recapitulate aspects enhance translatability mechanistic

Language: Английский

Citations

0

Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19 DOI Creative Commons
Shukur Wasman Smail,

Niaz Albarzinji,

Rebaz Hamza Salih

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: April 22, 2025

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent disease 2019 (COVID-19), in late initiated a global health crisis marked by widespread infection, significant mortality, and long-term implications. While SARS-CoV-2 primarily targets system, recent findings indicate that it also significantly disrupts human microbiome, particularly gut microbiota, contributing to severity, systemic inflammation, immune dysregulation, increased susceptibility secondary infections chronic conditions. Dysbiosis, or microbial imbalance, exacerbates clinical outcomes COVID-19 has been linked long-COVID, condition affecting proportion survivors manifesting with over 200 symptoms across multiple organ systems. Despite growing recognition microbiome alterations COVID-19, precise mechanisms which interacts influences progression remain poorly understood. This narrative review investigates impact on host-microbiota dynamics evaluates its implications severity for developing personalized therapeutic strategies COVID-19. Furthermore, highlights dual role modulating progression, as promising target advancing diagnostic, prognostic, approaches managing

Language: Английский

Citations

0

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

Beyond chemicals: Opportunities and challenges of integrating non-chemical stressors in adverse outcome pathways DOI Creative Commons
Laure‐Alix Clerbaux, Julija Filipovska, Penny Nymark

et al.

ALTEX, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

The adverse outcome pathways (AOPs) were developed to accelerate evidence-based chemical risk assessment by leveraging data from new approach methodologies. Thanks their stressor-agnostic approach, AOPs seen as instrumental in other fields. Here, we present that report non-chemical stressors along with the challenges encountered for development. Challenges regarding linked nanomaterials include non-specific molecular initiating events, limited understanding of nanomaterial biodistribution, and needs adaptations silico modeling testing systems. Development radiation face how incorporate ionizing events type, dose rate, energy deposition, account targeting multiple macromolecules. COVID-19 required inclusion SARS-CoV-2-specific replicative steps capture essential driving disease. Developing evaluate efficacy toxicity cell therapies necessitates addressing cellular nature therapeutic function stressor. Finally, emerging biological like microbial pesticides can learn AOPs. We further discuss needed expand AOP applicability beyond chemicals are mainly at levels while downstream key tissue or organ level, such inflammation, shared many initiated various stressors. In conclusion, although it is challenging integrate within AOPs, this expands opportunities real-world scenarios, identify vulnerable individuals, bridge knowledge on mechanisms adversity. Plain language summaryThe pathway (AOP) framework was help predict whether have toxic effects humans. Structuring available information an accessible database reduce animal testing. usually path interaction a stressor, chemical, human body outcome, e.g., disease symptom. concept has now been expanded nanomaterials, radiation, viruses, cells used treat patients, microorganisms employed pesticides. use these need be accommodated point out share inflammation By integrating into framework, scenarios where people may exposed different stressor types considered, individuals identified, compounded.

Language: Английский

Citations

9

Infection with SARS-CoV-2 Is Associated with Elevated Levels of IP-10, MCP-1, and IL-13 in Sepsis Patients DOI Creative Commons
Tanja Eichhorn, Silke Huber, René Weiss

et al.

Diagnostics, Journal Year: 2023, Volume and Issue: 13(6), P. 1069 - 1069

Published: March 11, 2023

Immunothrombosis, an excessive inflammatory response with simultaneous overactivation of the coagulation system, is a central pathomechanism in sepsis and COVID-19. It associated cellular activation, vascular damage, microvascular thrombosis, which can lead to multiple organ failure death. Here, we characterized factors related immunothrombosis plasma samples from 78 patients. In course routine clinical testing, SARS-CoV-2 was detected 14 these Viral infection higher mortality. Both, COVID-19 negative positive patients showed increased levels effectors immunothrombosis, including platelet factor 4, D-dimer, nucleosomes, citrullinated histone H3, high mobility group box-1 protein, as well phosphatidylserine-expressing platelet-derived extracellular vesicles, compared healthy controls (n = 25). Using 27-plex cytokine bead array, found that Interleukin (IL)-1ra, IL-6, IL-8, IL-13, tumor necrosis (TNF)-α, interferon inducible protein (IP)-10, monocyte chemotactic (MCP)-1, macrophage (MIP)-1α, granulocyte-colony stimulating (G-CSF) were elevated both, patients, controls. IP-10, MCP-1, while all other mediators widely overlapped between

Language: Английский

Citations

8