Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders DOI Creative Commons
Xiaopo Cheng, Christina Caruso, Wilbur A. Lam

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 18, 2023

Red blood cell (RBC) disorders affect billions worldwide. While alterations in the physical properties of aberrant RBCs and associated hemodynamic changes are readily observed, conditions such as sickle disease iron deficiency, RBC can also be with vascular dysfunction. The mechanisms vasculopathy those diseases remain unclear scant research has explored whether biophysical directly function. Here we hypothesize that purely interactions between endothelial cells, due to margination stiff RBCs, play a key role this phenomenon for range disorders. This hypothesis is tested by direct simulations cellular scale computational model flow disease, deficiency anemia, COVID-19, spherocytosis. We characterize distributions normal mixtures straight curved tubes, latter address issues geometric complexity arise microcirculation. In all cases strongly localize near vessel walls (margination) contrasts size, shape, deformability from cells. channel, distribution marginated cells very heterogeneous, indicating geometry. Finally, shear stresses on walls; consistent our hypothesis, generate large transient stress fluctuations high velocity gradients induced their near-wall motions. anomalous experienced may responsible observed inflammation.

Language: Английский

Pathophysiological, immunological, and inflammatory features of long COVID DOI Creative Commons
Karen Böhmwald, Benjamín Diethelm‐Varela,

Linmar Rodríguez-Guilarte

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 28, 2024

The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social economic burdens on nations. While most of the attention therapeutic efforts have concentrated acute phase disease, a notable proportion survivors experience persistent symptoms post-infection clearance. This diverse set symptoms, loosely categorized as long COVID, presents potential additional public health crisis. It is estimated that 1 5 exhibit clinical manifestations consistent with COVID. Despite this prevalence, mechanisms pathophysiology COVID remain poorly understood. Alarmingly, evidence suggests cases within condition develop debilitating or disabling symptoms. Hence, urgent priority should be given further studies equip systems for its management. review provides an overview available information emerging condition, focusing affected individuals’ epidemiology, pathophysiological mechanisms, immunological inflammatory profiles.

Language: Английский

Citations

19
Fe-Capsaicin Nanozymes Attenuate Sepsis-Induced Acute Lung Injury via NF-κB Signaling DOI Creative Commons
Ruijie Wang, Quan Li,

Pengxin Wu

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 73 - 90

Published: Jan. 1, 2024

Background: In sepsis, the lungs are one of most severely affected organs, usually resulting in acute lung injury (ALI). Capsaicin (CAP) is a natural compound found chili peppers that has pain-relieving and anti-inflammatory properties. Here, we report nanoparticles containing capsaicin iron (Fe-CAP NPs) exhibited effects treatment ALI. Methods: The morphological characteristics nanozymes were detected. RAW 264.7 cells divided into four groups: control, lipopolysaccharide (LPS), CAP+LPS Fe-CAP+LPS groups. expression inducible nitric oxide synthase (iNOS), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) was assessed by immunofluorescence, Western blot, enzyme-linked immunosorbent assay (ELISA). Nuclear factor kappa-B (NF-κB) determined blot. C57 mice LPS, Interleukin-6 (IL-6) iNOS detected Blot. IL-6 TNF-α serum ELISA. Extravasated Evans blue, histopathological evaluation wet-to-dry (W/D) weight ratio used to assess pulmonary capillary permeability. blood major organs (heart, liver, spleen, kidney) tested for toxicity Fe-CAP NPs. Results: LPS group, TNF-α, iNOS, p-NF-κB p-IKBα increased. However, their significantly decreased group. TGF-β showed opposite trend. vivo, notably increased group but with pretreatment. ameliorated EB leakage, improved histopathology tissue reduced W/D ratio. non-cytotoxicity, when studying these biological activities. Conclusion: NPs could alleviated inflammation inhibiting pro-inflammatory factors macrophages, increasing factors, alleviating damage. Keywords: capsaicin, macrophage, nanoparticles,

Language: Английский

Citations

13
The role of thromboinflammation in acute kidney injury among patients with septic coagulopathy DOI
Toshiaki Iba, Julie Helms, Cheryl L. Maier

et al.

Journal of Thrombosis and Haemostasis, Journal Year: 2024, Volume and Issue: 22(6), P. 1530 - 1540

Published: Feb. 19, 2024

Language: Английский

Citations

8
Four years into the pandemic, managing COVID-19 patients with acute coagulopathy: what have we learned? DOI
Toshiaki Iba, Jerrold H. Levy, Cheryl L. Maier

et al.

Journal of Thrombosis and Haemostasis, Journal Year: 2024, Volume and Issue: 22(6), P. 1541 - 1549

Published: Feb. 29, 2024

Language: Английский

Citations

6
Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives DOI Creative Commons

Yikan Sun,

Can Wang,

Peiquan Lin

et al.

World Journal of Pediatrics, Journal Year: 2024, Volume and Issue: 20(4), P. 307 - 324

Published: Feb. 6, 2024

Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise the pediatric population with debilitating systemic impacts can be fatal at times, meriting further attention from clinicians. Meanwhile, intricate interactions between pathogen virulence factors host defense mechanisms are believed play indispensable roles COVID-19 pathophysiology but remain incompletely understood.

Language: Английский

Citations

4
Expression profiling of circular RNAs in sepsis-induced acute gastrointestinal injury: insights into potential biomarkers and mechanisms DOI Creative Commons
Xiaojun Liu, Chenxi Li,

Chengying Hong

et al.

Cytotechnology, Journal Year: 2025, Volume and Issue: 77(2)

Published: Jan. 25, 2025

This study aimed to investigate the role of circular RNAs (circRNAs) in sepsis-induced acute gastrointestinal injury (AGI), focusing on their potential as biomarkers and involvement disease progression. Peripheral blood samples from 14 patients with AGI healthy volunteers were collected. RNA sequencing was performed profile circRNA miRNA expression. Differential expression analysis identified key regulatory RNAs. Functional enrichment conducted explore biological pathways, circRNA-miRNA interaction networks constructed. Significant differences profiles observed between controls. Several circRNAs, including hsa_circ_0008381 hsa_circ_0071375, exhibited stepwise increases correlating severity. indicated that host genes differentially expressed circRNAs are involved processes like protein ubiquitination, organelle maintenance, cellular signaling pathways such mitochondrial biogenesis lipid metabolism. CircRNA-miRNA suggested sponges, regulating downstream processes. demonstrated diagnostic therapeutic targets for AGI. Further research is warranted validate clinical utility unravel mechanistic roles

Language: Английский

Citations

0
Metabolomics Profiling Reveals Critical Roles of Indoxyl Sulfate in the Regulation of Innate Monocytes in COVID-19 DOI Creative Commons
Liqing He, Yunke Wang, Fang Yuan

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 256 - 256

Published: Feb. 11, 2025

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is intricately related to the reprogramming of host metabolism. However, existing studies have mainly focused on peripheral blood samples and barely identified specific metabolites that are critically involved in pathology disease 2019 (COVID-19). In current small-scale study, we performed metabolic profiling plasma (n = 61) paired bronchoalveolar lavage fluid (BALF) 20) using parallel two-dimensional liquid chromatography–mass spectrometry (2DLC-MS). addition, studied how an metabolite regulates immunopathogenesis COVID-19. results unveiled distinct metabolome changes between healthy donors, moderate patients both BALF, indicating locations severity play critical roles COVID-19 alteration. Notably, a vital metabolite, indoxyl sulfate, was found be elevated BALF patients. Indoxyl sulfate selectively induced TNF-α production, reduced co-stimulatory signals, enhanced apoptosis human monocytes. Moreover, its levels negatively correlated with strength signals antigen presentation capability monocytes Collectively, our findings suggest could potentially serve as functional biomarker monitor progression guide more individualized treatment for

Language: Английский

Citations

0
Neutrophils: Linking Inflammation to Thrombosis and Unlocking New Treatment Horizons DOI Open Access
Haokun Li, Wei Shan, Xi Zhao

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1965 - 1965

Published: Feb. 25, 2025

Neutrophils play a key role in inflammatory responses and thrombosis, but their complex interactions disease pathogenesis are not fully understood. This review examines the multifaceted roles of neutrophils, focusing on activation, cytokine release, formation neutrophil extracellular traps (NETs), which contribute to host defense thrombosis. We discuss interaction between inflammation coagulation, direct effect neutrophils thrombus stability, involvement pathological thrombotic diseases. The therapeutic potential drug loading treatment as well clinical implications future research directions, highlighted. aim this is gain insight into critical neutrophil-inflammation-thrombus axis its target for diseases suggest possible directions neutrophil-loaded therapy

Language: Английский

Citations

0
Fgl2 regulates FcγRIIB+CD8+ T cell responses during infection DOI Creative Commons
Anna B. Morris, Max W. Adelman, Kelsey B. Bennion

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: 10(7)

Published: April 7, 2025

While the inhibitory receptor FcγRIIB has been shown to be upregulated on activated CD8+ T cells in both mice and humans, its effect cell fate during infection not fully elucidated. We identified an increase FcγRIIB-expressing patients with COVID-19 relative healthy controls as well mouse models of viral infection. Despite well-known role Fc receptor, also ligates immunosuppressive cytokine Fgl2, resulting apoptosis. Both chronic LCMV humans resulted a significant plasma Fgl2. Transfer into Fgl2-replete, but Fgl2-devoid, environment elimination FcγRIIB+, FcγRIIB-, cells. Similarly, Fgl2 was directly proportional lymphopenia COVID-19. RNA-Seq analysis demonstrated that produced by murine virus-specific cells, elicited versus acute from controls. In summary, production underpinned FcγRIIB-mediated loss immunity humans.

Language: Английский

Citations

0
Comparing the immune abnormalities in MIS-C to healthy children and those with inflammatory disease reveals distinct inflammatory cytokine production and a monofunctional T cell response DOI Creative Commons
Claire Butters, Ntombi Benede, Thandeka Moyo-Gwete

et al.

Clinical Immunology, Journal Year: 2023, Volume and Issue: 259, P. 109877 - 109877

Published: Dec. 22, 2023

Multisystem inflammatory syndrome in children (MIS-C) is a severe, hyperinflammatory disease that occurs after exposure to severe acute respiratory coronavirus 2 (SARS-CoV-2). The underlying immune pathology of MIS-C incompletely understood, with limited data comparing clinically similar paediatric febrile diseases at presentation. SARS-CoV-2-specific T cell responses have not been compared these groups assess whether there profile unique MIS-C. In this study, we measured cytokine concentration and humoral immunity fever suspected presentation (n = 83) where was ultimately confirmed 58) or another diagnosis made 25) healthy 91). Children exhibited distinctly elevated serum IL-10, IL-6, CRP No differences were detected SARS-CoV-2 spike IgG concentration, neutralisation capacity, antibody dependant cellular phagocytosis, cytotoxicity frequency between the groups. Healthy seropositive had higher proportion polyfunctional CD4+ cells those other infectious diagnoses, who both presented largely monofunctional profile. Treatment steroids and/or intravenous immunoglobulins resulted rapid reduction cytokines but did affect data, specific response.

Language: Английский

Citations

6