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Molecular Research on the Pathology and Treatment of Sepsis and Non-Infectious Inflammatory Conditions

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 2794

Special Issue Editor


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Guest Editor
Department of Physiological Sciences, Universidade Estadual de Londrina, Londrina, Brazil
Interests: sepsis; inflammation; immunology

Special Issue Information

Dear Colleagues,

Sepsis and non-infectious inflammatory disorders are significant global health challenges, and they are associated with a high prevalence of morbidity and mortality. Although our understanding of immune responses has advanced in recent years, the complex interactions within inflammatory networks and how they become dysregulated during disease remain incompletely understood. Molecular studies have been crucial in elucidating the mechanisms that promote inflammation, identifying biomarkers, and suggesting novel therapeutic targets.

This Special Issue welcomes the submission of original research and reviews that address the molecular mechanisms involved in sepsis and sterile inflammation, including leukocyte recruitment, efferocytosis, cytokine signaling, oxidative stress, and resolution pathways. We welcome contributions that investigate the impact of comorbidities on the progression of disease and provide molecular insights into how underlying conditions influence inflammation and clinical outcomes. Contributions related to novel anti-inflammatory therapies, drug development, and translational research are also encouraged.

This Special Issue aims to enhance our understanding of inflammation in order to support the development of innovative therapies.

Dr. Andressa Freitas
Guest Editor

Manuscript Submission Information

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Keywords

  • sepsis
  • comorbidities
  • inflammation
  • molecular mechanisms
  • cytokine signaling
  • oxidative stress
  • leukocyte recruitment
  • therapeutic targets

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Published Papers (1 paper)

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Research

27 pages, 3675 KB  
Article
Integrated Transcriptomic Analysis of S100A8/A9 as a Key Biomarker and Therapeutic Target in Sepsis Pathogenesis and AI Drug Repurposing
by Kirtan Dave, Alejandro Pazos-García, Natia Tamarashvili, Jose Vázquez-Naya and Cristian R. Munteanu
Int. J. Mol. Sci. 2025, 26(22), 11186; https://doi.org/10.3390/ijms262211186 - 19 Nov 2025
Cited by 1 | Viewed by 2393
Abstract
Sepsis is a life-threatening condition driven by a dysregulated immune response, leading to systemic inflammation and multi-organ failure. Among the key molecular regulators, S100A8/A9 has emerged as a critical damage-associated molecular pattern (DAMP) protein, amplifying pro-inflammatory signaling via the Toll-like receptor 4 (TLR4) [...] Read more.
Sepsis is a life-threatening condition driven by a dysregulated immune response, leading to systemic inflammation and multi-organ failure. Among the key molecular regulators, S100A8/A9 has emerged as a critical damage-associated molecular pattern (DAMP) protein, amplifying pro-inflammatory signaling via the Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) pathways. Elevated S100A8/A9 levels correlate with disease severity, making it a promising biomarker and therapeutic target. To unravel the role of S100A8/A9 in sepsis, we integrate scRNA-seq and RNA-seq approaches. scRNA-seq enables cell-type-specific resolution of immune responses, uncovering cellular heterogeneity, state transitions, and inflammatory pathways at the single-cell level. In contrast, RNA-seq provides a comprehensive view of global transcriptomic alterations, allowing robust statistical analysis of differentially expressed genes. The integration of both approaches enables precise deconvolution of immune cell contributions, validation of cell-specific markers, and identification of potential therapeutic targets. Our findings highlight the S100A8/A9-driven inflammatory cascade, its impact on immune cell interactions, and its potential as a diagnostic and prognostic biomarker in sepsis. Eight protein targets resulted from the integrative transcriptomics studies (corresponding to S100A8, S100A9, S100A6, NAMPT, FTH1, B2M, KLF6 and SRGN) have been used to predict interaction affinities with 2958 ChEMBL approved drugs, by using a pre-trained AI models (PLAPT) in order to point directions on drug repurposing in sepsis. The strongest predicted interactions have been confirmed with molecular docking and molecular dynamics analysis. This study underscores the power of combining high-throughput transcriptomics to advance our understanding of sepsis pathophysiology and develop precision medicine strategies. Full article
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