scholarly journals Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections

2020 ◽  
Author(s):  
Joann Diray-Arce ◽  
Maria-Giulia Conti ◽  
Boryana Petrova ◽  
Naama Kanarek ◽  
Asimenia Angelidou ◽  
...  
Keyword(s):  
Host Response ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
High Dimensional ◽  
Molecular Signatures ◽  
Biochemical Pathway ◽  
Innate And Adaptive Immunity ◽  
Health And Disease ◽  
Fresh Insight ◽  
Insight Into

Approaches to identification of metabolites have progressed from early biochemical pathway evaluation to modern high dimensional metabolomics which is a powerful tool to identify and characterize biomarkers of health and disease. While traditionally considered relevant in the context of classic metabolic diseases, immunometabolism has emerged as an important area of study as leukocytes generate key metabolites important to innate and adaptive immunity. Herein we discuss the metabolomic signatures and pathways perturbed during infection as well as vaccination. For example, changes in lipid and amino acid pathways (e.g., tryptophan, serine, and threonine) have been noted during infection while carbohydrate and bile acid pathways have shift upon vaccination. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying host response to infection and vaccination, and its integration with other systems biology platforms will add further impact to our studies of health and disease.

scholarly journals Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 492
Author(s):  
Joann Diray-Arce ◽  
Maria Giulia Conti ◽  
Boryana Petrova ◽  
Naama Kanarek ◽  
Asimenia Angelidou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Nucleotide Metabolism ◽  
Human Immune System ◽  
Innate And Adaptive Immunity ◽  
Health And Disease ◽  
Human Immune ◽  
Fresh Insight ◽  
Insight Into

Approaches to the identification of metabolites have progressed from early biochemical pathway evaluation to modern high-dimensional metabolomics, a powerful tool to identify and characterize biomarkers of health and disease. In addition to its relevance to classic metabolic diseases, metabolomics has been key to the emergence of immunometabolism, an important area of study, as leukocytes generate and are impacted by key metabolites important to innate and adaptive immunity. Herein, we discuss the metabolomic signatures and pathways perturbed by the activation of the human immune system during infection and vaccination. For example, infection induces changes in lipid (e.g., free fatty acids, sphingolipids, and lysophosphatidylcholines) and amino acid pathways (e.g., tryptophan, serine, and threonine), while vaccination can trigger changes in carbohydrate and bile acid pathways. Amino acid, carbohydrate, lipid, and nucleotide metabolism is relevant to immunity and is perturbed by both infections and vaccinations. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying the host immune response. Its integration with other systems biology platforms will enhance studies of human health and disease.

Defects in cytochrome oxidase assembly in humans: lessons from yeastThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 859-869 ◽  
Author(s):  
Jennifer M. Zee ◽  
D. Moira Glerum
Keyword(s):  
Molecular Mechanisms ◽  
Inner Mitochondrial Membrane ◽  
Yeast Saccharomyces Cerevisiae ◽  
Assembly Pathway ◽  
Complex Process ◽  
Health And Disease ◽  
Molecular Bases ◽  
Near Future ◽  
Insight Into ◽  
Selection Of

The biogenesis of the inner mitochondrial membrane enzyme cytochrome c oxidase (COX) is a complex process that requires the actions of ancillary proteins, collectively called assembly factors. Studies with the yeast Saccharomyces cerevisiae have provided considerable insight into the COX assembly pathway and have proven to be a fruitful model for understanding the molecular bases for inherited COX deficiencies in humans. In this review, we focus on critical steps in the COX assembly pathway. These processes are conserved from yeast to humans and are known to be involved in the etiology of human COX deficiencies. The contributions from our studies in yeast suggest that this organism remains an excellent model system for delineating the molecular mechanisms underlying COX assembly defects in humans. Current progress suggests that a complete picture of COX assembly will be achieved in the near future.

scholarly journals Peroxisomal Hydrogen Peroxide Metabolism and Signaling in Health and Disease

2019 ◽  
Vol 20 (15) ◽  
pp. 3673 ◽  
Author(s):  
Lismont ◽  
Revenco ◽  
Fransen
Keyword(s):  
Hydrogen Peroxide ◽  
Molecular Mechanisms ◽  
Signaling Network ◽  
H2o2 Production ◽  
Peroxisomal Enzyme ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Precise Role ◽  
Insight Into

Hydrogen peroxide (H2O2), a non-radical reactive oxygen species generated during many (patho)physiological conditions, is currently universally recognized as an important mediator of redox-regulated processes. Depending on its spatiotemporal accumulation profile, this molecule may act as a signaling messenger or cause oxidative damage. The focus of this review is to comprehensively evaluate the evidence that peroxisomes, organelles best known for their role in cellular lipid metabolism, also serve as hubs in the H2O2 signaling network. We first briefly introduce the basic concepts of how H2O2 can drive cellular signaling events. Next, we outline the peroxisomal enzyme systems involved in H2O2 metabolism in mammals and reflect on how this oxidant can permeate across the organellar membrane. In addition, we provide an up-to-date overview of molecular targets and biological processes that can be affected by changes in peroxisomal H2O2 metabolism. Where possible, emphasis is placed on the molecular mechanisms and factors involved. From the data presented, it is clear that there are still numerous gaps in our knowledge. Therefore, gaining more insight into how peroxisomes are integrated in the cellular H2O2 signaling network is of key importance to unravel the precise role of peroxisomal H2O2 production and scavenging in normal and pathological conditions.

scholarly journals Intestinal Fructose and Glucose Metabolism in Health and Disease

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 94 ◽  
Author(s):  
Beatriz Merino ◽  
Cristina M. Fernández-Díaz ◽  
Irene Cózar-Castellano ◽  
German Perdomo
Keyword(s):  
Glucose Metabolism ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Sugar Metabolism ◽  
Sugar Consumption ◽  
Cellular Mechanisms ◽  
Obesity And Diabetes ◽  
Health And Disease ◽  
Dietary Sugars

The worldwide epidemics of obesity and diabetes have been linked to increased sugar consumption in humans. Here, we review fructose and glucose metabolism, as well as potential molecular mechanisms by which excessive sugar consumption is associated to metabolic diseases and insulin resistance in humans. To this end, we focus on understanding molecular and cellular mechanisms of fructose and glucose transport and sensing in the intestine, the intracellular signaling effects of dietary sugar metabolism, and its impact on glucose homeostasis in health and disease. Finally, the peripheral and central effects of dietary sugars on the gut–brain axis will be reviewed.

scholarly journals Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 178
Author(s):  
Federica Barutta ◽  
Stefania Bellini ◽  
Marilena Durazzo ◽  
Gabriella Gruden
Keyword(s):  
Global Health ◽  
Clinical Data ◽  
Host Response ◽  
Intervention Studies ◽  
Metabolic Diseases ◽  
Causal Link ◽  
Experimental Animals ◽  
Mechanistic Insight ◽  
Bidirectional Relationship ◽  
Insight Into

Periodontitis and diabetes are two major global health problems despite their prevalence being significantly underreported and underestimated. Both epidemiological and intervention studies show a bidirectional relationship between periodontitis and diabetes. The hypothesis of a potential causal link between the two diseases is corroborated by recent studies in experimental animals that identified mechanisms whereby periodontitis and diabetes can adversely affect each other. Herein, we will review clinical data on the existence of a two-way relationship between periodontitis and diabetes and discuss possible mechanistic interactions in both directions, focusing in particular on new data highlighting the importance of the host response. Moreover, we will address the hypothesis that trained immunity may represent the unifying mechanism explaining the intertwined association between diabetes and periodontitis. Achieving a better mechanistic insight on clustering of infectious, inflammatory, and metabolic diseases may provide new therapeutic options to reduce the risk of diabetes and diabetes-associated comorbidities.

scholarly journals Do skeletal muscle-secreted factors influence the function of pancreatic β-cells?

2018 ◽  
Vol 314 (4) ◽  
pp. E297-E307 ◽  
Author(s):  
Jonathan P. Barlow ◽  
Thomas P. Solomon
Keyword(s):  
Skeletal Muscle ◽  
Cross Talk ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Ongoing Research ◽  
Secreted Factors ◽  
Health And Disease ◽  
Endocrine Signaling

Skeletal muscle is an endocrine organ that secretes a variety of compounds including proteins (myokines), metabolites, microRNAs (miRNAs), and exosomes, many of which are regulated by exercise and play important roles in endocrine signaling. Interorgan communication via muscle-secreted factors therefore provides a novel area for investigation and implicates the importance of skeletal muscle in the pathophysiology of metabolic diseases such as type 2 diabetes (T2D). Given that underlying molecular mechanisms of T2D are subject of ongoing research, in light of new evidence it is probable that interorgan cross-talk between skeletal muscle and pancreatic β-cells plays an important part. To date, the number of studies published in this field provide the basis of this review. Specifically, we discuss current experimental evidence in support for a role of skeletal muscle to β-cell cross-talk, paying particular attention to muscle-secreted factors including myokines, metabolites, miRNAs, and factors contained within exosomes that influence the function and/or the survival of β-cells in health and disease. In reviewing this evidence, we provide an update on the list of known muscle-secreted factors that have potential to influence the function and/or survival of β-cells under normal and diabetic conditions. We also report limitations of current cross-talk methods and discuss future directions in this growing field.

Astrocytes in health and disease

2007 ◽  
Vol 148 (15) ◽  
pp. 697-702 ◽  
Author(s):  
Marianna Murányi ◽  
Zsombor Lacza
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Free Radicals ◽  
Molecular Mechanisms ◽  
Neuronal Dysfunction ◽  
Supporting Cells ◽  
Neuronal Synapses ◽  
Health And Disease ◽  
Novel Targets ◽  
Therapeutic Tools

It is now known that astrocytes are not merely supporting cells but they also play an important role in neuronal funcions. Astrocytes tightly ensheat neuronal synapses and regulate the excitation of neurons by uptaking neurotransmitters; reglulate the cerebral blood flow, cerebral fluid volume and extracellular concentrations of ions. They also supply fuel in the form of lactate and provide free radical scavangers such as glutathione for active neurons. These facts indicate that impaired function of astrocytes may lead to neuronal dysfunction. After brain injury (stroke, trauma or tumors) astrocytes are swollen and release active molecules such as glutamate or free radicals resulting in neuronal dysfunction. Thus, investigation of the molecular mechanisms of astrocyte function may reveal novel targets for the development of therapeutic tools in neuronal diseases.

Periodontal Pathogens and Neuropsychiatric Health

2020 ◽  
Vol 20 (15) ◽  
pp. 1353-1397 ◽  
Author(s):  
Abhishek Wadhawan ◽  
Mark A. Reynolds ◽  
Hina Makkar ◽  
Alison J. Scott ◽  
Eileen Potocki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Grade ◽  
Periodontal Pathogens ◽  
Synergistic Interactions ◽  
Brain Vasculature ◽  
Micro Rnas ◽  
Clinical Conditions ◽  
Low Grade Inflammation ◽  
Neuropsychiatric Illness

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.

Upcoming Drifts In Bio-Similars

2020 ◽  
Vol 15 ◽  
Author(s):  
Geeta Aggarwal ◽  
Manju Nagpal ◽  
Ameya Sharma ◽  
Vivek Puri ◽  
Gitika Arora Dhingra
Keyword(s):  
Metabolic Diseases ◽  
Market Competition ◽  
Current Status ◽  
Medicinal Products ◽  
The Past ◽  
Biologic Activity ◽  
Emerging Trends ◽  
Regulatory Guidelines ◽  
Food Drug Administration ◽  
Insight Into

Background: Biopharmaceuticals such as Biologic medicinal products have been in clinical use over the past three decades and have benefited towards the therapy of degenerative and critical metabolic diseases. It is forecasted that market of biologics will be going to increase at a rate of 20% per year, and by 2025, more than ˃ 50% of new drug approvals may be biological products. The increasing utilization of the biologics necessitates for cost control, especially for innovators products that have enjoyed a lengthy period of exclusive use. As the first wave of biopharmaceuticals is expired or set to expire, it has led to various opportunities for the expansion of bio-similars i.e. copied versions of original biologics with same biologic activity. Development of biosimilars is expected to promote market competition, meet worldwide demand, sustain the healthcare systems and maintain the incentives for innovation. Methods: Appraisal of published articles from peer reviewed journals, PubMed literature, latest news and guidelines from European Medicine Agency, US Food Drug Administration (FDA) and India are used to identify data for review. Results: Main insight into the quality requirements concerning biologics, current status of regulation of biosimilars and upcoming challenges lying ahead for the upgrading of marketing authorization of bio-similars has been incorporated. Compiled literature on therapeutic status, regulatory guidelines and the emerging trends and opportunities of biosimilars has been thoroughly stated. Conclusion: Updates on biosimilars will support to investigate the possible impact of bio-similars on healthcare market.

scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

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