Key players in the regulation of iron homeostasis at the host-pathogen interface DOI Creative Commons

Inam Ullah,

Minglin Lang

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

Published: Oct. 24, 2023

Iron plays a crucial role in the biochemistry and development of nearly all living organisms. starvation pathogens during infection is striking feature utilized by host to quell infection. In mammals some other animals, iron essentially obtained from diet recycled erythrocytes. Free cytotoxic readily available invading pathogens. During infection, most utilize for their survival. Therefore, ensure limited free iron, host’s natural system denies this metal process termed nutritional immunity. fierce battle hosts win over pathogens, but others have evolved mechanisms overdrive barriers. Production siderophores, heme thievery, direct binding transferrin lactoferrin bacterial receptors are pathogens’ successful strategies which highlighted review. The intricate interplay between alteration systems understanding defense pathogen virulence. This review aims elucidate current propose future research directions enhance our knowledge field.

Language: Английский

Recentrifuge: Robust comparative analysis and contamination removal for metagenomics DOI Creative Commons
Jose Manuel Martí

PLoS Computational Biology, Journal Year: 2019, Volume and Issue: 15(4), P. e1006967 - e1006967

Published: April 8, 2019

Metagenomic sequencing is becoming widespread in biomedical and environmental research, the pace increasing even more thanks to nanopore sequencing. With a rising number of samples data per sample, challenge efficiently comparing results within specimen between specimens arises. Reagents, laboratory, host related contaminants complicate such analysis. Contamination particularly critical low microbial biomass body sites environments, where it can comprise most sample if not all. Recentrifuge implements robust method for removal negative-control crossover taxa from rest samples. Recentrifuge, researchers analyze taxonomic classifiers using interactive charts with emphasis on confidence level classifications. In addition contamination-subtracted samples, provides shared exclusive thus enabling contamination comparative analysis clinical metagenomics. Regarding first area, Recentrifuge's novel approach has already demonstrated its benefits showing that microbiomes Arctic Antarctic solar panels display similar profiles. field, confirm ability complex metagenomes, we challenged coming metagenomic investigation RNA plasma suffered point preventing any positive conclusion. provided yielded new biological insight into problem, supporting growing evidence blood microbiota healthy individuals, mostly translocated gut, oral cavity, genitourinary tract. We also developed synthetic dataset carefully designed rate algorithm, which significant improvement specificity while retaining high sensitivity presence cross-contaminants. official website www.recentrifuge.org. The source code are anonymously freely available GitHub PyPI. computing licensed under AGPLv3. Wiki extensive continually-updated documentation covering installation, use cases, testing, other useful topics.

Language: Английский

Citations

81

Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases DOI Creative Commons

Doortje Dekens,

Ulrich Eisel,

Leonie Gouweleeuw

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 70, P. 101414 - 101414

Published: July 26, 2021

Chronic (neuro)inflammation plays an important role in many age-related central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease and vascular dementia. Inflammation also characterizes conditions that form a risk factor for these CNS disorders, such as physical inactivity, obesity cardiovascular disease. Lipocalin 2 (Lcn2) is inflammatory protein shown to be involved different well thereof. Lcn2 expression increased the periphery brain diseases their conditions. Experimental studies indicate contributes various neuropathophysiological processes of exacerbated neuroinflammation, cell death iron dysregulation, which may negatively impact cognitive function. We hypothesize levels result sensitize increase develop diseases. In this review we first provide comprehensive overview known functions Lcn2, its effects CNS. Subsequently, explores potential (neuro)inflammatory link between development disorders. Altogether, evidence convincingly indicates key constituent ageing

Language: Английский

Citations

62

Comparison of Blood Bacterial Communities in Periodontal Health and Periodontal Disease DOI Creative Commons

David C. Emery,

Tanya L. Cerajewska,

Joon Seong

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2021, Volume and Issue: 10

Published: Jan. 5, 2021

The use of Next Generation Sequencing (NGS) techniques has generated a wide variety blood microbiome data. Due to the large variation in bacterial DNA profiles between studies and likely high concentrations cell-free blood, it is still not clear how such data relates viable microbiota. For these reasons much remains be understood about true nature any possible healthy microbiota bacteraemic events associated with disease. gut, reproductive tracts, skin, oral cavity are all sources blood-borne bacteria. Oral bacteria, especially those periodontal diseases, also commonly cardiovascular diseases as infective endocarditis, have been linked rheumatoid arthritis Alzheimer’s Periodontal treatment, dental probing, toothbrushing shown cause transient bacteraemia bacteria from phyla Firmicutes (e.g. Streptococci ) Bacteroidetes Porphyromonas found lesions (CVD). Many content however, find Proteobacteria dominant component, suggesting gut origin. Most this type total extracted either whole or fractions, buffy coat. Here, using method that purifies intact cells only, we examined donated by active, severe periodontitis periodontally controls show 43–52% species classified oral. Firmicutes, consisting largely members Streptococcus mitis group Staphylococcus epidermidis , were predominant at 63.5% sequences detected health and, little changed 66.7% periodontitis. Compared here relatively low levels 13.3% 17.6% health. This study reveals significant phylogenetic differences population when comparing disease cohorts.

Language: Английский

Citations

57

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications DOI Creative Commons
Douglas B. Kell, Etheresia Pretorius

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(16), P. 1653 - 1708

Published: Aug. 31, 2022

Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety acute circumstances. We argue here that I-R injury also underpins elements pathology chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be fibrin amyloid microclot blockage capillaries, for instance as exercise started; reperfusion necessary corollary when it finishes. rehearse mechanistic evidence these occurrences here, terms their manifestation oxidative stress, hyperinflammation, mast cell activation, production marker metabolites related activities. Such microclot-based phenomena can explain both breathlessness/fatigue post-exertional malaise observed conditions, many other observables. The recognition processes implies, mechanistically, therapeutic benefit potentially to had from antioxidants, anti-inflammatories, iron chelators, suitable, safe fibrinolytics, and/or anti-clotting agents. review considerable existing consistent with this, biochemical mechanisms involved.

Language: Английский

Citations

52

Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses DOI Creative Commons
J. Massimo Nunes, Douglas B. Kell, Etheresia Pretorius

et al.

Blood Reviews, Journal Year: 2023, Volume and Issue: 60, P. 101075 - 101075

Published: March 20, 2023

ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae COVID-19 (PASC), post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms ME/CFS. Disease presentation similar between two conditions, and subset COVID patients meet diagnostic criteria Since characterized by significant vascular pathology – including endothelial dysfunction, coagulopathy, dysregulation question whether not same biological abnormalities are significance in arises. Cardiac have while now been documented cohorts, recent studies demonstrating major deficits cerebral blood flow, hence dysregulation. A growing body research accompanied platelet hyperactivation, anomalous clotting, procoagulant phenotype, dysfunction. Endothelial damage dysregulated clotting can impair substance exchange tissues, result hypoperfusion, which may contribute manifestation certain symptoms. Here we review literature summarize cardiovascular haematological findings condition, and, this context, briefly discuss potential role previously-implicated pathogens. Overall, cardiac present within cohorts. While atherosclerotic heart disease significantly ME/CFS, suboptimal function defined reduced output, impaired are, these do appear influenced deconditioning. Rather, dysfunction (autonomic) nervous system. Plenty recently published hyperactivity as well processes. It particular importance determine what extent symptom severity, if systems targeted therapeutic purposes. Viral reservoirs herpesviruses exist most likely directly indirectly. This highlights studying functioning, vasculature, coagulation system

Language: Английский

Citations

23

Ferroptosis as an emerging target in rheumatoid arthritis DOI Creative Commons
Hui Zhao, Cheng Tang, Miao Wang

et al.

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

Published: Oct. 19, 2023

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. Due to the rise in incidence rate RA and limitations existing therapies, search for new treatment strategies has become a global focus. Ferroptosis novel programmed cell death characterized by iron-dependent lipid peroxidation, with distinct differences from apoptosis, autophagy, necrosis. Under conditions iron accumulation glutathione peroxidase 4 (GPX4) activity loss, lethal peroxide direct cause ferroptosis. mediates inflammation, oxidative stress, damage processes, also participates occurrence pathological progression inflammatory joint diseases including RA. This review provides insight into role mechanism ferroptosis discusses potential challenges as therapeutic strategy RA, effort provide targets prevention treatment.

Language: Английский

Citations

23

The Relationship Between Inflammatory Markers and Supraventricular Tachycardia in Children DOI Creative Commons

Sevval Durgut,

Hikmet Kıztanır, Yasin Yıldız

et al.

International Journal of Cardiovascular Sciences, Journal Year: 2025, Volume and Issue: 38

Published: Jan. 1, 2025

Language: Английский

Citations

1

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity DOI Creative Commons
Amy D. Proal, Trevor G Marshall

Frontiers in Pediatrics, Journal Year: 2018, Volume and Issue: 6

Published: Dec. 4, 2018

The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens be studied interacting members of communities. Humans harbor these vast ecosystems bacteria, viruses and fungi in nearly all tissue blood. Most well-studied inflammatory conditions are dysbiosis or imbalance microbiome. While gut identified ME/CFS, microbes outside can also contribute illness. Pathobionts, their associated proteins/metabolites, often control metabolism gene expression a manner that pushes body towards state Intracellular pathogens, including many with drive by directly interfering transcription, translation, DNA repair processes. Molecular mimicry between host pathogen proteins/metabolites further complicates this interference. Other disable mitochondria dysregulate nervous system signaling. Antibodies and/or clonal T cells patients likely activated response persistent pathogens. Different have evolved similar survival mechanisms immune metabolic pathways. dysfunction driven organisms result clusters symptoms. may pathogen-induced dysfunction, nature symptom presentation varying based patient’s unique environmental history. Under conditions, would benefit from treatments support an effort reverse disease process.

Language: Английский

Citations

70

Colorectal cancer is associated with increased circulating lipopolysaccharide, inflammation and hypercoagulability DOI Creative Commons
Greta M. de Waal,

Willem J.S. de Villiers,

Tim Forgan

et al.

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: May 29, 2020

Abstract Gut dysbiosis contributes to the development of a dysfunctional gut barrier, facilitating translocation bacteria and inflammagens, is implicated in colorectal cancer (CRC) pathogenesis. Such ‘leaky gut’ conditions result systemic inflammation, which hallmark increased hypercoagulability. Fluorescence antibody confocal microscopy was used determine circulating levels lipopolysaccharide (LPS) control CRC populations. Here we showed that LPS are significantly elevated population. We also markers inflammation hypercoagulability this Furthermore, anomalous blood clotting structural changes components presented. Importantly, association between levels, hematological dysfunction analysed. Statistical regression models were applied identify with strong CRC, investigate correlation markers. A core aim enhanced biomarker discovery for CRC. conclude can promote contribute pathological coagulation system, resulting chronic an activated system tumorigenesis. Blood-based screening tools emerging research area interest screening. propose use additional (novel) biomarkers effectively screen

Language: Английский

Citations

66

Prevalence of readily detected amyloid blood clots in ‘unclotted’ Type 2 Diabetes Mellitus and COVID-19 plasma: a preliminary report DOI Creative Commons
Etheresia Pretorius, Chantelle Venter,

Gert Jacobus Laubscher

et al.

Cardiovascular Diabetology, Journal Year: 2020, Volume and Issue: 19(1)

Published: Nov. 17, 2020

Type 2 Diabetes Mellitus (T2DM) is a well-known comorbidity to COVID-19 and coagulopathies are common accompaniment both T2DM COVID-19. In addition, patients with known develop micro-clots within the lungs. The rapid detection of uses genotypic testing for presence SARS-Cov-2 virus in nasopharyngeal swabs, but it can have poor sensitivity. A rapid, host-based physiological test that indicated clotting severity extent pathologies individual who was infected or not would be highly desirable.

Language: Английский

Citations

66