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Biomedicines
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Molecular Biomarkers and More Efficient Therapies for Sepsis—2nd Edition
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Molecular Biomarkers and More Efficient Therapies for Sepsis—2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 3793

Special Issue Editors

Dr. Wen-Lin Su

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Guest Editor
1. Division of Pulmonary and Critical Care Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No.289, Jianguo Rd., Xindian Dist., New Taipei City 23142, Taiwan
2. School of Medicine, Tzu Chi University, Hualien, No.289, Jianguo Rd., Xindian Dist., New Taipei City 23142, Taiwan
Interests: sepsis; COVID-19; biomarkers; pneumonia
Special Issues, Collections and Topics in MDPI journals
Dr. Chih-Hao Shen

E-Mail Website
Guest Editor
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Interests: acute lung injury; macrophages; alveolar epithelium
Dr. Sheng-Kang Chiu

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Guest Editor
1. Division of Infectious Diseases, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation. No. 289, Jianguo Rd., Xindian Dist., New Taipei City 23142, Taiwan
2. School of Medicine, Tzu Chi University, Hualien. No. 289, Jianguo Rd., Xindian Dist., New Taipei City 23142, Taiwan
Interests: antimicrobial resistance; klebsiella pneumoniae; sepsis; virulence
Special Issues, Collections and Topics in MDPI journals
Dr. Yi-Ting Chen

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Guest Editor
1. Department of Critical Care Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien City, Taiwan
2. School of Medicine, Tzu Chi University, Hualien. No. 707, Sec. 3, Zhongyang Rd., Hualien City 970473, Taiwan
Interests: sepsis; critical care; tuberculosis; pneumonia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sepsis is a life-threatening condition arising from a dysregulated host response to infection, and it remains a critical global health challenge. Its progression often leads to multiple organ dysfunction and significant morbidity and mortality. The pathophysiology of sepsis involves a complex interplay between immune cells, platelets, and other host systems, which work together to combat pathogens but can also result in severe inflammation and organ damage.

Currently, the clinical diagnosis of sepsis relies on the Sequential Organ Failure Assessment (SOFA) score, which measures the severity of organ failure. However, the identification of molecular biomarkers—released either by the host or the pathogen during infection—has opened new avenues for understanding sepsis progression, enhancing diagnostic accuracy, and guiding the development of more effective therapeutic interventions.

We invite you to contribute original research articles, reviews, or short communications that explore recent advances in molecular biomarkers and their role in defining sepsis severity, improving diagnostic methods, and developing more efficient therapies. Submissions addressing signal transduction mechanisms, inflammatory pathways, pathogen–host interactions, and innovative therapeutic approaches are particularly welcome.

Dr. Wen-Lin Su
Dr. Chih-Hao Shen
Dr. Sheng-Kang Chiu
Dr. Yi-Ting Chen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sepsis
  • organ dysfunction
  • inflammatory process
  • molecular biomarkers
  • pathogen infection
  • signal transduction mechanisms

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Published Papers (3 papers)

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Research

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14 pages, 681 KB  
Article
Distinct Plasma LPC Signatures Differentiate COVID-19 Sepsis from Other Sepsis Aetiologies
by Vlad Pavel, Patricia Mester, Marcus Höring, Gerhard Liebisch, Stephan Schmid, Martina Müller and Christa Buechler
Biomedicines 2025, 13(9), 2110; https://doi.org/10.3390/biomedicines13092110 - 29 Aug 2025
Viewed by 662
Abstract
Background/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl [...] Read more.
Background/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl ester levels are higher in patients with SARS-CoV-2 infection than in patients without, and this study analysed whether this may extend to differences in LPC, a bioactive constituent of lipoproteins. Methods: The plasma levels of 13 LPC species were measured by flow injection analysis tandem mass spectrometry (FIA-MS/MS) in 157 patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock. Of these patients, 24 had SARS-CoV-2 infection. Results: Patients with SIRS exhibited higher plasma levels of the minor LPC species LPC 15:0 and 22:4 compared to those with sepsis or septic shock. Five LPC species were also reduced in the plasma of 31 patients with liver cirrhosis; therefore, patients with cirrhosis or SIRS were excluded from subsequent analyses. Compared to 76 non-COVID-19 patients with sepsis or septic shock, SARS-CoV-2 infection in 21 patients was associated with significantly higher plasma levels of ten individual LPC species and total LPC concentration. In patients with sepsis/septic shock, LPC species showed negative correlations with procalcitonin and interleukin-6, and positive correlations with gamma-glutamyltransferase and cholesteryl ester levels. In contrast, no significant associations were observed between LPC levels and C-reactive protein, aminotransferases, or free cholesterol. Conclusions: Differential LPC levels, despite comparable disease severity, may serve as metabolic biomarkers to distinguish SARS-CoV-2 sepsis from other causes of sepsis and inform targeted therapeutic approaches. Full article
(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis—2nd Edition)
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Review

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31 pages, 1533 KB  
Review
Immunodynamic Disruption in Sepsis: Mechanisms and Strategies for Personalized Immunomodulation
by Jhan S. Saavedra-Torres, María Virginia Pinzón-Fernández, Humberto Alejandro Nati-Castillo, Valentina Cadena Correa, Luis Carlos Lopez Molina, Juan Estaban Gaitán, Daniel Tenorio-Castro, Diego A. Lucero Guanga, Marlon Arias-Intriago, Andrea Tello-De-la-Torre, Alice Gaibor-Pazmiño and Juan S. Izquierdo-Condoy
Biomedicines 2025, 13(9), 2139; https://doi.org/10.3390/biomedicines13092139 - 2 Sep 2025
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Abstract
Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection. It follows a dynamic course in which early hyperinflammation coexists and overlaps with progressive immune suppression, a process best described as immunodynamic disruption. Key mechanisms include extensive lymphocyte death, expansion [...] Read more.
Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection. It follows a dynamic course in which early hyperinflammation coexists and overlaps with progressive immune suppression, a process best described as immunodynamic disruption. Key mechanisms include extensive lymphocyte death, expansion of regulatory T cells, impaired antigen presentation, and persistent activation of inhibitory checkpoints such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4). These changes reduce immune competence and increase vulnerability to secondary infections. Clinically, reduced expression of Human Leukocyte Antigen–DR (HLA-DR) on monocytes and persistent lymphopenia have emerged as robust biomarkers for patient stratification and timing of immunomodulatory therapies. Beyond the acute phase, many survivors do not achieve full immune recovery but instead develop a Persistent Immune Remnant, defined as long-lasting immune, metabolic, and endothelial dysfunction despite apparent clinical resolution. Recognizing PIR emphasizes the need for long-term monitoring and biomarker-guided interventions to restore immune balance. To integrate these observations, we propose the SIMMP–Sepsis model (Sepsis-Associated Persistent Multiorgan Immunometabolic Syndrome), which links molecular dysfunction to clinical trajectories and provides a framework for developing precision immunotherapies. This perspective reframes sepsis not only as an acute crisis but also as a chronic immunometabolic syndrome, where survival marks the beginning of active immune restoration. Full article
(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis—2nd Edition)
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31 pages, 721 KB  
Review
The Epigenetics of Sepsis: How Gene Modulation Shapes Outcomes
by Giulia Pignataro, Cristina Triunfo, Andrea Piccioni, Simona Racco, Mariella Fuorlo, Evelina Forte, Francesco Franceschi and Marcello Candelli
Biomedicines 2025, 13(8), 1936; https://doi.org/10.3390/biomedicines13081936 - 8 Aug 2025
Viewed by 1351
Abstract
Sepsis is a complex and heterogeneous condition, arising from a disrupted immune response to infection that can progress to organ failure and carries a high risk of death. In recent years, growing attention has been paid to the role of epigenetic mechanisms—including DNA [...] Read more.
Sepsis is a complex and heterogeneous condition, arising from a disrupted immune response to infection that can progress to organ failure and carries a high risk of death. In recent years, growing attention has been paid to the role of epigenetic mechanisms—including DNA methylation, histone modifications, non-coding RNAs, and RNA methylation—in shaping immune activity during sepsis. These processes affect immune functions such as macrophage polarization, cytokine release, and the exhaustion of immune cells, and they help explain the shift from an initial phase of overwhelming inflammation to a later state of immune suppression. Epigenetic alterations also contribute to tissue-specific damage, notably in the lungs, kidneys, and heart, and have been linked to disease severity and clinical prognosis. Advances in transcriptomic and epigenetic profiling have made it possible to distinguish molecular subtypes of septic patients, each with distinct immune features and varied responses to treatments such as corticosteroids and metabolic therapies. Emerging biomarkers—like AQP5 methylation, histone lactylation (H3K18la), and m6A RNA methylation—are opening new options for patient classification and more tailored therapeutic strategies. This review examines the current understanding of how epigenetic regulation contributes to the pathophysiology of sepsis and considers its implications for developing more individualized approaches to care. Full article
(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis—2nd Edition)
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