Dataset Information

Nafamostat Mesilate Improves Sepsis Outcomes by Modulating Complement and Coagulation Pathways

ABSTRACT: Supporting data for: Nafamostat Mesilate Improves Sepsis Outcomes by Modulating Complement and Coagulation Pathways

ORGANISM(S): Homo Sapiens

SUBMITTER: Ming Zhong

PROVIDER: PXD074871 | iProX | Tue Feb 24 00:00:00 GMT 2026

REPOSITORIES: iProX

ACCESS DATA

Publications

Nafamostat mesilate improves sepsis outcomes by modulating complement and coagulation pathways.

He Qiaolan Q Yang Yuanjun Y Xie Zhuxin Z Wu Yuanyuan Y Yang Chenghang C Qian Yiqi Y Zhong Ming M

Journal of advanced research 20260416

<h4>Introduction</h4>Sepsis is a leading cause of mortality in critically ill patients, characterized by dysregulation of multiple biological systems, including the complement, coagulation and contact pathways Nafamostat (NM), a serine protease inhibitor, has shown potential in modulating these systems.<h4>Objectives</h4>We investigated the potential therapeutic role of NM in sepsis and its mechanism.<h4>Methods</h4>High-throughput mass spectrometry proteomics analysis was conducted to investiga ...[more]

PMID: 41999944

Similar Datasets

Project description:# Background Acute kidney injury (AKI) in sepsis patients increases patient mortality. Endothelial cells are important players in the pathophysiology of sepsis-associated AKI (SA-AKI), yet knowledge regarding their spatiotemporal involvement in coagulation disbalance and leukocyte recruitment is lacking. This study investigated the identity and kinetics of responses of different microvascular compartments in kidney cortex in response to SA-AKI. # Methods Laser microdissected arterioles, glomeruli, peritubular capillaries, and postcapillary venules from kidneys of mice subjected to cecal ligation and puncture (CLP) were analyzed using RNA sequencing. Differential expression and pathway enrichment analyses identified genes involved in coagulation and inflammation. A selection of these genes was evaluated by RT-qPCR in microvascular compartments of renal biopsies from patients with SA-AKI. The role of two identified genes in lipopolysaccharide-induced endothelial coagulation and inflammatory activation were determined in vitro in HUVEC using siRNA-based gene silencing. # Results CLP-sepsis in mice induced altered expression of approximately 400 genes in the renal microvasculature, with microvascular compartments exhibiting unique spatiotemporal responses. In mice, changes in gene expression related to coagulation and inflammation were most extensive in glomeruli at early and intermediate time points, with high induction of Plat, Serpine1, Thbd, Icam1, Stat3, and Ifitm3. In human SA-AKI, PROCR and STAT3 were induced in postcapillary venules, while SERPINE1 expression was diminished. IFITM3 was increased in arterioles and glomeruli. In vitro studies revealed that STAT3 and IFITM3 partly control endothelial coagulation and inflammatory activation. # Conclusion Renal microvascular compartments in mice and humans exhibited heterogeneous changes in coagulation- and inflammation-related gene expression in response to SA-AKI. Additional research should aim at understanding the functional consequences of the here described heterogeneous microvascular responses to establish the usefulness of identified genes as therapeutic targets in SA-AKI.

Project description:Background: The role of viral infections as a mediator of systemic immune dysfunction leading to sepsis has received limited attention compared to the bacterial pathogens. The COVID-19 pandemic and the increased cases of sepsis in the absence of known bacterial pathogens have highlighted the clinical relevance of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolic characteristics to shed light on the molecular mechanisms underlying the pathological conditions of viral sepsis in COVID-19. Methods: We retrospectively analyzed data from 231 hospitalized patients with confirmed COVID-19 admitted to three hospitals in China. The presence of viral sepsis was diagnosed with SOFA score ≥ 2 in the absence of bacterial infection. Demographics, clinical, and laboratory parameters, as well as clinical outcomes, were obtained from electronic chart reviews. Plasma samples were obtained from a subset of these patients (23 patients in the Viral Non-Sepsis [VNS] group and 14 patients in the Viral Sepsis [VS] group) to analyze proteomic and metabolic profiles. Findings: The viral sepsis group exhibited severe disease, as indicated by elevated markers of both pulmonary (ARDS) and systemic disease (liver, kidney, and cardiac injury). Consistent with known immune paralysis observed in sepsis, subjects with viral sepsis were more susceptible to secondary infections by bacterial and fungal pathogens. Overall, viral sepsis led to an increased length of ICU stay, required invasive mechanical ventilation and a significant increase in mortality compared to the non-viral sepsis group. At the molecular levels, we identified unique metabolic and proteomic signatures that suggest a substantial contribution of the coagulation and platelet dysfunction pathways to systemic pathologies. Interpretation: Viral sepsis presents an underrecognized threat contributing to high mortality. Specific metabolic and proteomic changes demonstrated coagulation and platelet dysfunction as key pathological pathway in viral sepsis.

Dataset Information

Nafamostat Mesilate Improves Sepsis Outcomes by Modulating Complement and Coagulation Pathways

Publications

Nafamostat mesilate improves sepsis outcomes by modulating complement and coagulation pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets