Emerging role of neutrophil extracellular traps in the complications of diabetes mellitus

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Aug. 23, 2022

Immune dysfunction is widely regarded as one of the central tenants underpinning pathophysiology diabetes mellitus (DM) and its complications. When discussing immunity, role neutrophils must be accounted for: are most abundant circulating immune cells first to recruited sites inflammation, where they contribute host defense via phagocytosis, degranulation, extrusion neutrophil extracellular traps (NETs). NETs composed DNA associated with nuclear cytosolic proteins. Although originally reported an antimicrobial strategy prevent microbial dissemination, a growing body evidence has implicated in various autoimmune metabolic disorders. In these disorders, propagate pathologic inflammatory response consequent tissue injury thrombosis. Many diabetic complications—such stroke, retinopathy, impaired wound healing, coronary artery disease—involve mechanisms. Therefore, this review, we discuss laboratory clinical data informing our understanding development NET markers, including myeloperoxidase, citrullinated histone H3, elastase, cell-free double-stranded DNA, can easily measured serum or detected immunohistochemical/immunocytochemical staining specimens. constituents potentially constitute reliable biomarkers for use management patients. However, no NET-targeting drug currently approved treatment complications; candidate will require outcomes well-designed, robust trials assessing whether inhibition benefit patients terms morbidity, quality life, health expenditures, mortality. much work remains done translating encouraging pieces into medications used clinic.

Language: Английский

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Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

Nutrients, Journal Year: 2022, Volume and Issue: 14(13), P. 2602 - 2602

Published: June 23, 2022

Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with higher risk of morbidity and severe course COVID-19. Our study aimed to evaluate the effects cholecalciferol supplementation on clinical features inflammatory markers in patients A serum 25(OH)D determined 311 COVID-19 patients. Among them, 129 were then randomized into two groups similar concomitant medication. Group I (n = 56) received bolus at dose 50,000 IU first eighth days hospitalization. Patients from II 54) did not receive supplementation. We found significant differences between preferential increase Δ ninth day hospitalization (p < 0.001). The negatively number bed (r −0.23, p 0.006); we observe other benefits receiving an oral cholecalciferol. Moreover, I, neutrophil lymphocyte counts significantly 0.04; 0.02), while C-reactive protein lower 0.02). 100,000 cholecalciferol, compared those without supplementation, decrease frequencies CD38++CD27 transitional CD27−CD38+ mature naive B cells 0.006 0.02) CD27−CD38− DN Thus, rise caused by vitamin insufficient deficient may positively affect immune status hence

Language: Английский

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Heterogenous CD8+ T Cell Maturation and ‘Polarization’ in Acute and Convalescent COVID-19 Patients

Viruses, Journal Year: 2022, Volume and Issue: 14(9), P. 1906 - 1906

Published: Aug. 28, 2022

The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding role of in acute phase COVID-19 post-COVID-19 syndrome are still limited.. Peripheral blood samples collected from patients with (n = 71), convalescent subjects bearing serum N-protein-specific IgG antibodies 51), healthy volunteers no detectable to any proteins (HC, n 46) were analyzed using 10-color flow cytometry.Patients vs. HC convalescents showed decreased absolute numbers whereas frequency CM TEMRA was elevated. had increased naïve compared HC. Cell-surface CD57 highly expressed by majority subsets during COVID-19, on 'naïve', CM, EM4, pE1 2-3 months post-symptom onset. CXCR5 expression altered subjects, frequencies CXCR3+ CCR4+ both patient groups CCR6-expressing cells. Moreover, CXCR3+CCR6- Tc1 convalescents, Tc2 Tc17 levels Finally, IL-27 negatively correlated CCR6+ patients.We described an abnormal cell profile which resulted lower effector (TEMRA Tc1), higher senescent state (upregulated 'naïve' memory cells), expressing lung tissue mucosal homing molecules (Tc2, Tc17, Tc17.1). Thus, our indicate that can impact long-term response.

Language: Английский

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Neutrophil extracellular traps and long COVID

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

Published: Sept. 27, 2023

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by significant number survivors. The underlying pathophysiology COVID has become topic intense research discussion. While chronic inflammation in received considerable attention, the role neutrophils, which are most abundant all immune cells and primary responders to inflammation, been unfortunately overlooked, perhaps due their short lifespan. In this review, we discuss emerging neutrophil extracellular traps (NETs) persistent inflammatory response observed patients. We present early evidence linking persistence NETs pulmonary fibrosis, cardiovascular abnormalities, neurological dysfunction COVID. Several uncertainties require investigation future studies. These include mechanisms SARS-CoV-2 brings about sustained activation phenotypes after infection resolution; whether heterogeneity neutrophils seen acute persists into phase; presence autoantibodies can induce protect them from degradation; exert differential, organ-specific effects; specifically NET components contribute pathologies, such fibrosis; senescent drive formation through pro-inflammatory secretome Answering these questions may pave way for development clinically applicable strategies targeting NETs, providing relief health crisis.

Language: Английский

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Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

Nutrients, Journal Year: 2023, Volume and Issue: 15(5), P. 1285 - 1285

Published: March 4, 2023

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The efficacy safety bovine were evaluated in LAC randomized double-blind placebo-controlled trial. A total 218 hospitalized adult patients moderate-to-severe COVID-19 receive 800 mg/die oral (n = 113) or placebo 105), both given combination standard therapy. No differences vs. observed primary outcomes: proportion death intensive care unit admission (risk ratio 1.06 (95% CI 0.63–1.79)) discharge National Early Warning Score 2 (NEWS2) ≤ within 14 days from enrollment (RR 0.85 0.70–1.04)). Lactoferrin showed an excellent tolerability profile. Even though safe tolerable, our results do not support its use

Language: Английский

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COVID-19 Biomarkers at the Crossroad between Patient Stratification and Targeted Therapy: The Role of Validated and Proposed Parameters

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7099 - 7099

Published: April 12, 2023

Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of great heterogeneity disease manifestations, a precise patient stratification at admission is still difficult, thus rendering rational allocation limited medical resources as well tailored therapeutic approach challenging. To date, many hematologic biomarkers been validated to support early triage SARS-CoV-2-positive patients monitor their progression. Among them, some indices proven be not only predictive parameters, but also direct or indirect pharmacological targets, allowing for more single-patient symptoms, especially in those with severe progressive disease. While blood test-derived parameters quickly entered routine clinical practice, other circulating proposed by several researchers who investigated reliability specific cohorts. Despite usefulness contexts potential interest such experimental markers implemented mainly due higher costs low availability general hospital settings. This narrative review will present an overview most commonly adopted practice promising ones emerging from population studies. Considering that each reflects aspect evolution, embedding new highly informative into testing could help stratification, guiding timely method intervention.

Language: Английский

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Diabetes Mellitus, Energy Metabolism, and COVID-19

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 45(2), P. 281 - 308

Published: Nov. 2, 2023

Abstract Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute chronic manifestations, but also alters energy metabolism. Such metabolic alterations can lead to dysglycemia long-lasting effects. Thus, the pandemic has potential a further rise of pandemic. This review outlines how preexisting spanning from excess visceral adipose tissue hyperglycemia overt may exacerbate severity. We summarize different effects SARS-CoV-2 infection on key organs tissues orchestrating metabolism, including tissue, liver, skeletal muscle, pancreas. Last, we provide an integrative view derangements that occur during COVID-19. Altogether, this allows better understanding occurring when fire starts small flame, thereby help reducing impact

Language: Английский

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Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 951 - 951

Published: Jan. 4, 2023

Gas6 (growth arrest-specific gene 6) is a widely expressed vitamin K-dependent protein that involved in many biological processes such as homeostatic regulation, inflammation and repair/fibrotic processes. It known it the main ligand of TAMs, tyrosine kinase receptor family three members, namely MerTK, Tyro-3 Axl, for which displays highest affinity. Gas6/TAM axis activation to be modulating inflammatory responses well fibrotic evolution different pathological conditions. Due rapidly evolving COVID-19 pandemic, this review will focus on SARS-CoV-2 infection, where de-regulated fibrosis represent relevant feature severe disease manifestation. Furthermore, highlight most recent scientific evidence supporting an unsuspected role Axl infection driver, potential therapeutic advantages use existing inhibitors management. From physiological point view, plays dual role, fostering tissue repair or leading organ damage loss function, depending prevalence its anti-inflammatory profibrotic properties. This makes strong case further research focusing pharmacological target manage conditions, chronic COVID-19.

Language: Английский

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Advances in mechanical biomarkers

Journal of Molecular Recognition, Journal Year: 2023, Volume and Issue: 36(8)

Published: April 24, 2023

Abstract Mechanical biomarkers distinguish health conditions through quantitative mechanical measurements. The emergence and establishment of nanotechnology in the last decades have provided new tools to obtain at nanoscale. measurements are reproducible, label‐free, start be applied vivo can high throughput, require small samples. protocols clinical practice macro scale like palpation or blood pressure measurement routinely used by medical doctors. Nanotechnology brought sensing next scale, where cells, tissues, proteins probed linked conditions. changes cells tissues may detected before other markers, such as protein expression, providing an important advantage biomarkers. In present review, we explore biomarker's historical evolution, describe on various diseases novel discoveries nanomechanical field for their characterization. We conclude that establishing hallmarks diseases, several cases early diagnostics discovery drug targets involved changes, while advances instrumentation bringing commercial products into practice. along with testing niche market, whose demand is increasing due expansion personalized medicine unmet needs clinics.

Language: Английский

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Oncogenic potential of SARS-CoV-2—targeting hallmarks of cancer pathways

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 26, 2024

Language: Английский

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