LPS-induced extracellular AREG triggers macrophage pyroptosis through the EGFR/TLR4 signaling pathway DOI Creative Commons
Gang Yuan, Qian Qiao,

Aolin Jiang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Amphiregulin (AREG), a member of the EGF family, exists as transmembrane protein anchored to cell surface. In response external stimuli, its extracellular domain is released into matrix through paracrine or autocrine signaling. However, role in septic macrophage pyroptosis remains poorly understood. This study aims investigate AREG macrophages, mice, and patients. We found that high expression was regulated by RPLP1 at translation level, which increased IL-6, CCL2, CCL3 protein, well Caspase 1, IL-1β , Nlrp3 mRNA expression, resulting pyroptosis. Mechanistically, aggravated pretreatment, triggered ATP (adenosine 5′-triphosphate). The AREG-neutralizing antibody reduced LPS-induced epidermal growth factor receptor (EGFR) activation, TLR4 Extracellular AREG-induced decreased with EGFR NF-κB inhibition, Myd88 knockout. Additionally, DTT-pretreated suppressed vivo attenuates systemic inflammation infiltration delays survival mouse model. Furthermore, mediates sepsis humans, genes involved AREG-mediated signaling pathway were highly expressed patients severe compared those general moderate sepsis. Overall, EGFR/TLR4/Myd88/NF-κB pathway, providing promising treatment strategies for

Language: Английский

Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies DOI
Manu Shankar‐Hari, Thierry Calandra, Miguel P. Soares

et al.

The Lancet Respiratory Medicine, Journal Year: 2024, Volume and Issue: 12(4), P. 323 - 336

Published: Feb. 23, 2024

Language: Английский

Citations

39
Advances and Challenges in Sepsis Management: Modern Tools and Future Directions DOI Creative Commons
Elena Santacroce,

Miriam D’Angerio,

Alin Liviu Ciobanu

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 439 - 439

Published: March 2, 2024

Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte subsets, leading to diminished effector functions, altered cytokine profiles, metabolic changes. The complexity of sepsis stems not only from its pathophysiology also the heterogeneity patient responses, posing significant challenges developing universally effective therapies. review emphasizes importance phenotyping enhance patient-specific diagnostic therapeutic strategies. Phenotyping cells, which categorizes patients based on clinical immunological characteristics, is pivotal for tailoring treatment approaches. Flow cytometry emerges as crucial tool this endeavor, offering rapid, low cost detailed analysis cell populations their functional states. Indeed, technology facilitates understanding dysfunctions contributes identification novel biomarkers. Our underscores potential integrating flow with omics data, machine learning observations refine management, highlighting shift towards personalized medicine care. approach could lead more precise interventions, improving outcomes heterogeneously affected population.

Language: Английский

Citations

20
Sepsis and Septic Shock DOI
Nuala J. Meyer, Hallie C. Prescott

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(22), P. 2133 - 2146

Published: Dec. 4, 2024

Language: Английский

Citations

20
Enhancing sepsis biomarker development: key considerations from public and private perspectives DOI Creative Commons

Jean‐François Llitjos,

Enitan D. Carrol, Marcin F. Osuchowski

et al.

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: July 13, 2024

Implementation of biomarkers in sepsis and septic shock emergency situations, remains highly challenging. This viewpoint arose from a public-private 3-day workshop aiming to facilitate the transition into clinical practice. The authors consist international academic researchers clinician-scientists industry experts who gathered (i) identify current obstacles impeding biomarker research sepsis, (ii) outline important milestones critical path development (iii) discuss novel avenues discovery implementation. To define more appropriately potential place better understanding pathophysiology is mandatory, particular patient's trajectory early inflammatory onset late persisting immunosuppression phase. time-varying host response urges develop time-resolved test characterize persistence immunological dysfunctions. Furthermore, age-related difference has be considered between adult paediatric patients. In this context, numerous barriers adoption practice, such as lack consensus about diagnostic performances, absence strict recommendations for development, cost resources implications, methodological validation challenges or limited awareness education have been identified. Biomarker-guided interventions patients that would benefit therapy, sTREM-1-guided Nangibotide treatment Adrenomedullin-guided Enibarcimab treatment, appear promising but require further evaluation. Artificial intelligence also great field through capability analyse high volume complex data multiparametric patient endotypes trajectories. conclude, requires comprehensive multidisciplinary approach employing most advanced analytical tools, creation platform collaboratively merges scientific commercial needs support an expedited regulatory approval process.

Language: Английский

Citations

19
Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions DOI
Yibei Wang, Mohammed Safi, Fred R. Hirsch

et al.

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: 22(3), P. 200 - 214

Published: Jan. 6, 2025

Language: Английский

Citations

3
Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis DOI
Massimo Girardis, Sascha David, Ricard Ferrer

et al.

Intensive Care Medicine, Journal Year: 2024, Volume and Issue: 50(10), P. 1580 - 1592

Published: Sept. 2, 2024

Language: Английский

Citations

13
The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency DOI Open Access
George J. Kontoghiorghes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4654 - 4654

Published: April 25, 2024

The supply and control of iron is essential for all cells vital many physiological processes. All functions activities are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin chelator–iron complexes haem play major roles metabolism human physiology. Similarly, the mainstay treatments most common diseases metabolism, namely deficiency anaemia overload, involve iron–chelator iron-chelating drugs deferiprone (L1), deferoxamine (DF) deferasirox. Endogenous citric acid glutathione exogenous ascorbic also important homeostasis. Recent advances treatment effective ferric tri-maltol complex (feraccru or accrufer) transfusional overload using L1 L1/DF combinations have decreased associated mortality morbidity improved quality life millions patients. Many other chelating ciclopirox, dexrazoxane EDTA used daily by patients diseases. their metabolites iron-chelation capacity hydroxyurea, tetracyclines, anthracyclines aspirin, well dietary molecules gallic acid, caffeic quercetin, ellagic maltol phytochelators, known to interact affect related Different interactions observed presence essential, xenobiotic, diagnostic theranostic metal ions competing iron. Clinical trials Parkinson’s, Alzheimer’s neurodegenerative diseases, HIV infections, cancer, diabetic nephropathy inflammation, highlight importance chelation therapy clinical conditions. proposed use modulating ferroptosis signifies a new era design therapeutic strategies introduction artificial intelligence guidance optimal outcomes personalised medicine expected increase further impact medicine, survival metabolic disorders

Language: Английский

Citations

11
Recent Advances of Precision Immunotherapy in Sepsis DOI Creative Commons

Antonios Arapis,

Dimitrios Panagiotopoulos,

Evangelos J. Giamarellos‐Bourboulis

et al.

Burns & Trauma, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

Abstract Precision immunotherapy signifies the administration of required type immune intervention tailored to state activation at appropriate time window. The classification patients into different states is usually done by either a protein blood biomarker or molecular endotype that diagnostic precise state. Evidence coming from trials last decade suggests interventions should be split strategies aiming attenuate exaggerated responses, restore sepsis-induced immunoparalysis (SII) and vascular tone. Suggested responses are anakinra, nangibotide tocilizumab. Biomarkers guide their use ferritin, soluble triggering receptor expressed on myeloid cells-1 C-reactive protein. SII nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor IgM-enriched immunoglobulin prepapations. expression leukocyte antigen DR monocytes, absolute lymphocyte count levels M. One recently suggested strategy tone adrecizumab, which guided bio-adrenomedulin. these precision treatment still hampered need for large-scale randomized controlled trials.

Language: Английский

Citations

1
AQP3 and AQP9—Contrary Players in Sepsis? DOI Open Access

Patrick Thon,

Tim Rahmel,

Dominik Ziehe

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1209 - 1209

Published: Jan. 19, 2024

Sepsis involves an immunological systemic response to a microbial pathogenic insult, leading cascade of interconnected biochemical, cellular, and organ-organ interaction networks. Potential drug targets can depict aquaporins, as they are involved in processes. In immune cells, AQP3 AQP9 special interest. this study, we tested the hypothesis that these aquaporins expressed blood cells septic patients impact sepsis survival. Clinical data, routine laboratory parameters, samples from were analyzed on day 1 8 after diagnosis. AQP expression cytokine serum concentrations measured. mRNA increased over duration was correlated with lymphocyte count. High associated contrast, not altered during neutrophil count, low levels Furthermore, independent risk factor for lethality. conclusion, may play contrary roles pathophysiology sepsis, results suggest be novel target and, concurrently, valuable biomarker disease.

Language: Английский

Citations

7
Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy? DOI Open Access
Katharina Rump, Björn Koos,

Dominik Ziehe

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(1), P. 610 - 610

Published: Jan. 3, 2024

Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as 5 (Aqp5) knockdown provided enhanced sepsis survival in murine model. Potential AQP5 provide sulfonamides their derivatives. In this study, we tested hypothesis that reduce expression different conditions. The impact of on immune cell migration was examined lines REH RAW 264.7 qPCR, Western blot assay. Subsequently, whether furosemide methazolamide capable reducing after LPS incubation investigated whole blood samples healthy volunteers. Incubation with (10−5 M) (10−6 reduced mRNA protein about 30% cells. Pre-incubation cells towards SDF1-α compared non-preincubated control level. PBMCs led reduction LPS-induced levels, while failed it. Methazolamide appears However, administration, no longer possible. Hence, our study indicates has potential be used prophylaxis.

Language: Английский

Citations

5