scholarly journals Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Mussap ◽  
Vassilios Fanos
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Asymptomatic Infection ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Patient Specific ◽  
Wide Range ◽  
Life Threatening ◽  
The Individual ◽  
Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

Cancer and COVID-19: A proposed mechanism with therapeutic interventions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3135-3135
Author(s):  
Yan Leyfman ◽  
Nancy Emmanuel ◽  
Aleksey Tentler ◽  
Jared Cappelli ◽  
Timothy K Erick ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Organ Damage ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Actual Number ◽  
Data Registry ◽  
Number Of Patients ◽  
Increased Risk ◽  
Life Threatening ◽  
Active Cancer

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]

scholarly journals Vascular Dysfunction in Preeclampsia

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3055
Author(s):  
Megan A. Opichka ◽  
Matthew W. Rappelt ◽  
David D. Gutterman ◽  
Justin L. Grobe ◽  
Jennifer J. McIntosh
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Treatment Options ◽  
Cardiovascular Disorder ◽  
Endothelial Damage ◽  
Spiral Artery ◽  
Mitochondrial Stress ◽  
Inflammatory State ◽  
Life Threatening

Preeclampsia is a life-threatening pregnancy-associated cardiovascular disorder characterized by hypertension and proteinuria at 20 weeks of gestation. Though its exact underlying cause is not precisely defined and likely heterogenous, a plethora of research indicates that in some women with preeclampsia, both maternal and placental vascular dysfunction plays a role in the pathogenesis and can persist into the postpartum period. Potential abnormalities include impaired placentation, incomplete spiral artery remodeling, and endothelial damage, which are further propagated by immune factors, mitochondrial stress, and an imbalance of pro- and antiangiogenic substances. While the field has progressed, current gaps in knowledge include detailed initial molecular mechanisms and effective treatment options. Newfound evidence indicates that vasopressin is an early mediator and biomarker of the disorder, and promising future therapeutic avenues include mitigating mitochondrial dysfunction, excess oxidative stress, and the resulting inflammatory state. In this review, we provide a detailed overview of vascular defects present during preeclampsia and connect well-established notions to newer discoveries at the molecular, cellular, and whole-organism levels.

FEATURES OF RESIDUAL PHENOMENA AND CONSEQUENCES OF COVID-19 (REVIEW)

Vestnik ◽  
2021 ◽  
pp. 335-340
Author(s):  
Г.Н. Абуова ◽  
Г.А. Айтмуратова ◽  
Т.В. Полукчи ◽  
Ф.А. Бердалиева ◽  
Г.Г. Шаймерденова
Keyword(s):  
Asymptomatic Infection ◽  
Multiple Organ ◽  
Upper Respiratory Tract ◽  
Respiratory Tract Disease ◽  
Infected People ◽  
Life Threatening ◽  
Upper Respiratory ◽  
Tract Disease ◽  
Timely Treatment

Проведен литературный обзор об особенностях остаточных явлений и последствий COVID-19 на основе данных, опубликованных до настоящего времени. К началу января 2021 года COVID-19, сопровождающийся тяжелым острым респираторным синдромом, вызванным коронавирусом (SARS-CoV-2), привел к более чем 83 миллионам подтвержденных случаев и более чем 1,8 миллионам смертей. Клинический спектр инфекции SARS-CoV-2 широк, включая бессимптомную инфекцию, лихорадку, усталость, миалгии, легкое заболевание верхних дыхательных путей, тяжелую и опасную для жизни вирусную пневмонию, требующую госпитализации и летальный исход. COVID-19 - это новое заболевание, и остается неопределенность в отношении возможных долгосрочных последствий для здоровья. На сегодняшний день известно, что у большинства инфицированных, особенно в молодом возрасте, заболевание имеет легкое течение, по сравнению с лицами старшего возраста. У некоторых пациентов заболевание быстро прогрессирует и развиваются различные осложнения, в т.ч. полиорганная недостаточность. Поэтому раннее выявление и своевременное лечение критических случаев имеет решающее значение. A literature review on the features of residual phenomena and consequences of COVID-19 is analyzed on the basis of data published so far. By the beginning of January 2021, COVID-19, accompanied by severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2), led to more than 83 million confirmed cases and more than 1.8 million deaths. The clinical spectrum of SARS-CoV-2 infection is wide, including asymptomatic infection, fever, fatigue, myalgia, mild upper respiratory tract disease, severe and life-threatening viral pneumonia requiring hospitalization, and death. COVID-19 is a new disease, and uncertainty remains about possible long-term health consequences. To date, it is known that the majority of infected people, especially at a young age, have a mild course of the disease, compared with older people. In some patients, the disease progresses rapidly and various complications develop, including multiple organ failure. Therefore, early detection and timely treatment of critical cases is crucial.

scholarly journals Survey of the bp/tee genes from clinical group A streptococcus isolates in New Zealand – implications for vaccine development

2014 ◽  
Vol 63 (12) ◽  
pp. 1670-1678 ◽  
Author(s):  
John D. Steemson ◽  
Nicole J. Moreland ◽  
Deborah Williamson ◽  
Julie Morgan ◽  
Philip E. Carter ◽  
...  
Keyword(s):  
New Zealand ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
T Antigen ◽  
Clinical Group ◽  
Wide Range ◽  
Life Threatening ◽  
Group A ◽  
The Individual

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (>97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/T-antigen as a vaccine target.

scholarly journals Molecular mechanisms of inhibiting glucosyltransferases for biofilm formation in Streptococcus mutans

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Qiong Zhang ◽  
Qizhao Ma ◽  
Yan Wang ◽  
Hui Wu ◽  
Jing Zou
Keyword(s):  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Therapeutic Interventions ◽  
Extracellular Polysaccharides ◽  
Combination Strategies ◽  
Wide Range ◽  
Challenges And Opportunities ◽  
Virulence Property ◽  
Inhibitory Molecules

AbstractGlucosyltransferases (Gtfs) play critical roles in the etiology and pathogenesis of Streptococcus mutans (S. mutans)- mediated dental caries including early childhood caries. Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides (EPSs), the key virulence property in the cariogenic process. Therefore, Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms. Importantly, targeting Gtfs selectively impairs the S. mutans virulence without affecting S. mutans existence or the existence of other species in the oral cavity. Over the past decade, numerous Gtfs inhibitory molecules have been identified, mainly including natural and synthetic compounds and their derivatives, antibodies, and metal ions. These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness. Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies, which is more effective for inhibiting Gtfs than one drug or class of drugs. This review highlights our current understanding of Gtfs activities and their potential utility, and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.

scholarly journals The Contribution of Endothelial Dysfunction in Systemic Injury Subsequent to SARS-Cov-2 Infection

2020 ◽  
Vol 21 (23) ◽  
pp. 9309
Author(s):  
Jessica Maiuolo ◽  
Rocco Mollace ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Blood Vessels ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Vascular Complications ◽  
Therapeutic Interventions ◽  
The Impact

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease, leading to irreversible tissue damage and death of people with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

scholarly journals Viral Respiratory Pathogens and Lung Injury

2021 ◽  
Vol 34 (3) ◽  
Author(s):  
Nicola Clementi ◽  
Sreya Ghosh ◽  
Maria De Santis ◽  
Matteo Castelli ◽  
Elena Criscuolo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Damage ◽  
Clinical Manifestations ◽  
Upper Airway ◽  
Patient Specific ◽  
Respiratory Pathogens ◽  
Human Respiratory Tract ◽  
Immune Mediated ◽  
Life Threatening ◽  
Viral Respiratory

SUMMARY Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute respiratory distress syndrome (ARDS). As dramatically evident in the ongoing SARS-CoV-2 pandemic, the clinical picture is not always easily predictable due to the combined effect of direct viral and indirect patient-specific immune-mediated damage. In this review, we discuss the main RNA (orthomyxoviruses, paramyxoviruses, and coronaviruses) and DNA (adenoviruses, herpesviruses, and bocaviruses) viruses with respiratory tropism and their mechanisms of direct and indirect cell damage. We analyze the thin line existing between a protective immune response, capable of limiting viral replication, and an unbalanced, dysregulated immune activation often leading to the most severe complication. Our comprehension of the molecular mechanisms involved is increasing and this should pave the way for the development and clinical use of new tailored immune-based antiviral strategies.

Perspective of molecular hydrogen in the treatment of sepsis

2020 ◽  
Vol 26 ◽  
Author(s):  
Bo Qi ◽  
Yang Yu ◽  
Yaoqi Wang ◽  
Yuzun Wang ◽  
Yonghao Yu ◽  
...  
Keyword(s):  
Molecular Hydrogen ◽  
Host Response ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Multiple Organ ◽  
Medical Gas ◽  
Life Threatening ◽  
Apoptosis Regulation ◽  
Multiple Signaling ◽  
Anti Inflammation

: Sepsis is the main cause of death in critically ill patients with no effective treatment. Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. As a novel medical gas, molecular hydrogen (H2 ) has a therapeutic effect on many diseases, such as sepsis. H2 treatment exerts multiple biological effects, which can effectively improve multiple organ injuries caused by sepsis. However, the underlying molecular mechanisms of hydrogen involved in the treatment of sepsis remain elusive, which are likely related to anti-inflammation, anti-oxidation, anti-apoptosis, regulation of autophagy and multiple signaling pathways. This review can help to better understand the progress of hydrogen in the treatment of sepsis, and provide a theoretical basis for the clinical application of hydrogen therapy in sepsis in the future.

scholarly journals Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu-Lei Gao ◽  
Jian-Hua Zhai ◽  
Yan-Fen Chai
Keyword(s):  
Molecular Mechanisms ◽  
Secondary Infection ◽  
Multiple Organ ◽  
Host Responses ◽  
Severe Condition ◽  
Caspase 1 ◽  
Recent Advances ◽  
Increased Risk ◽  
Life Threatening ◽  
Minimize Tissue Damage

Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words “pyro” and “ptosis” in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.

Comorbidities and Hematopoietic Cell Transplantation Outcomes

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 237-247 ◽  
Author(s):  
Mohamed L. Sorror
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Multiple Organ ◽  
Hematopoietic Cell ◽  
Therapeutic Interventions ◽  
Patient Specific ◽  
Biological Aging ◽  
High Dose ◽  
Conditioning Regimens ◽  
Comorbidity Index

AbstractConventional allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for various hematological diseases due, in part to high-dose conditioning and, in part, to graft-versus-tumor effects. Reduced-intensity or non-myeloablative conditioning regimens have relied mostly on graft-versus-tumor effects for disease control, and their advent has allowed relatively older and medically infirm patients to be offered allo-HCT. However, both HCT modalities have been associated with organ toxicities and graft-versus-host disease, resulting in substantial non-relapse mortality. It has become increasingly important to optimize pre-transplant risk assessment in order to improve HCT decision making and clinical trial assignments. Single-organ comorbidity involving liver, lung, heart, or kidney before HCT has been traditionally found to cause organ toxicity after HCT. Recent efforts have resulted in the advent of a weighted scoring system that could sensitively capture multiple-organ comorbidities prior to HCT. The HCT-comorbidity index (HCT-CI) has provided better prediction of HCT-related morbidity and mortality than other non-HCT-specific indices. Subsequent studies, with the exception of a few studies with modest numbers of patients, have confirmed the prognostic importance of the HCT-CI. Further, the HCT-CI has been consolidated with various disease-specific and patient-specific risk factors to refine assignments of patients to the appropriate HCT setting. Ongoing studies are addressing prospective validation of the HCT-CI, furthering our understanding of biological aging, and enhancing the applicability of the HCT-CI comorbidity coding. Future knowledge of the impacts of multiple comorbidities on post-HCT toxicities might guide new prophylactic and therapeutic interventions to lessen the procedure's mortality.

Sign in / Sign up

Export Citation Format

Share Document