Daily Sepsis Research Analysis
Analyzed 27 papers and selected 3 impactful papers.
Summary
Three studies advance sepsis science across therapy, metabolism, and risk stratification. A systems pharmacology study identifies cynaroside as a dual TBK1/IKKβ inhibitor underlying Reduning injection’s anti-inflammatory effects and organ protection. A metabolomics study shows mitochondrial transplantation restores immune-cell bioenergetics in polymicrobial sepsis, while a prospective cohort demonstrates the lactate-to-albumin ratio robustly predicts shock, SA-AKI, and 28-day mortality.
Research Themes
- Dual-kinase inhibition of TBK1/IKKβ as an anti-inflammatory strategy in sepsis
- Mitochondrial transplantation to reprogram immune-cell metabolism
- Early prognostication using lactate-to-albumin ratio (LAR)
Selected Articles
1. A novel mechanism of Reduning injection in sepsis treatment: Targeting inflammatory kinases TBK1 and IKKβ.
Using integrated transcriptomics across six hyperinflammation cell models anchored to patient data, the authors prioritized NF-κB/TNF pathways and identified cynaroside as the principal active component of Reduning injection. Cynaroside dual-inhibited TBK1 (IC50 8.9 μM) and IKKβ (IC50 23.3 μM), suppressing NF-κB activation and cytokines in vitro, and reduced organ injury and systemic inflammation in LPS-induced septic rats.
Impact: This work reveals a concrete, drug-like mechanism—dual inhibition of TBK1 and IKKβ—linking a complex TCM formulation to actionable inflammatory targets in sepsis, supported by multi-omics and in vivo validation.
Clinical Implications: TBK1/IKKβ emerge as therapeutic targets for hyperinflammatory sepsis, with cynaroside as a tractable lead. Findings support precision anti-inflammatory strategies and rationalize clinical translation of Reduning or CYN-enriched derivatives.
Key Findings
- Systems-level prioritization identified NF-κB, TNF, and cytokine–receptor pathways as clinically anchored targets in sepsis.
- Cynaroside was the principal effective component, dual-inhibiting TBK1 (IC50 8.9 μM) and IKKβ (IC50 23.3 μM) to suppress NF-κB signaling and cytokine production.
- Molecular dynamics showed stable CYN–IKKβ and CYN–TBK1 complexes occupying catalytic pockets via key hydrogen bonds.
- In LPS-induced septic rats, RDN and CYN reduced IL-6/TNF-α, mitigated multi-organ injury, restored blood counts, and inhibited NF-κB activation in PBMCs.
Methodological Strengths
- Clinically anchored multi-omics framework across six hyperinflammation models
- Mechanistic validation spanning kinase assays, transcriptomics, molecular dynamics, and in vivo efficacy
Limitations
- Relies on LPS-induced sepsis rather than polymicrobial models
- No survival endpoints or human clinical validation reported
Future Directions: Evaluate CYN and TBK1/IKKβ dual inhibition in polymicrobial sepsis models and early-phase clinical trials; explore PK/PD, safety, and combination strategies with standard care.
BACKGROUND: Sepsis-induced systemic inflammation, characterized by immune dysregulation and cytokine storms, presents significant therapeutic challenges. Reduning injection (RDN), a Traditional Chinese Medicine formulation, demonstrates clinical efficacy in sepsis management, yet its molecular mechanisms remain elusive. PURPOSE: This study aimed to unravel RDN's immunomodulatory mechanisms and identify its core effective components targeting key inflammatory signaling networks in sepsis. METHODS: Initially, six com
2. Mitochondrial Transplantation Restores Immune Cell Metabolism in Sepsis: A Metabolomics Study.
In a rat polymicrobial sepsis model, GC-TOF-MS metabolomics of PBMCs and splenocytes showed that sepsis suppresses amino acid, carbohydrate, and lipid metabolites, including aspartic acid, glutamic acid, AMP, and myo-inositol. Mitochondrial transplantation partially restored these metabolites toward sham levels, reactivating TCA-cycle, nucleotide, and lipid pathways and supporting immune-cell bioenergetic recovery.
Impact: Provides direct metabolomic evidence that exogenous mitochondria reprogram immune-cell metabolism during sepsis, strengthening the mechanistic basis for mitochondrial therapeutics.
Clinical Implications: Supports development of mitochondrial transplantation or mitochondria-targeted therapies for sepsis; identifies metabolite pathways that could serve as pharmacodynamic biomarkers.
Key Findings
- Sepsis markedly suppressed amino acid, carbohydrate, and lipid metabolites (e.g., aspartic acid, glutamic acid, AMP, myo-inositol) in PBMCs and splenocytes.
- Mitochondrial transplantation partially restored metabolite levels toward sham, reactivating TCA cycle, nucleotide, and lipid pathways.
- Multivariate analyses (PCA/PLS-DA) revealed distinct clustering among sham, sepsis, and MT-treated groups.
- Pathway analysis confirmed reversal of metabolic suppression and bioenergetic recovery in immune cells after MT.
Methodological Strengths
- GC-TOF-MS metabolomics in two immune-cell compartments with multivariate statistics
- Comparative design across sham, sepsis, and MT groups in a polymicrobial model
Limitations
- Preclinical animal study without human validation or survival endpoints
- Sample size and dosing/safety parameters not detailed
Future Directions: Test MT across dosing/time windows with functional outcomes (survival, organ function), evaluate safety and immunologic effects, and pilot translation in early-phase human studies.
Sepsis induces severe immune and metabolic dysfunction driven by mitochondrial failure. Mitochondrial transplantation (MT) has emerged as a promising strategy to restore mitochondrial bioenergetics, but its metabolic impact on immune cells remains unclear. Here, we used gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics to evaluate metabolic alterations in peripheral blood mononuclear cells (PBMCs) and splenocytes from a rat polymicrobial sepsis model treated with
3. Association of lactate to albumin ratio with the severity and prognosis of patients with sepsis admitted to the emergency intensive care unit: A prospective cohort study.
In a single-center prospective cohort of adults with sepsis, the lactate-to-albumin ratio independently predicted septic shock, SA-AKI, and 28-day mortality. ROC analyses showed AUCs of 0.705 for shock (cutoff 0.106), 0.762 for SA-AKI (cutoff 0.097), and 0.863 for 28-day mortality (cutoff 0.098), with risk increasing across LAR quartiles.
Impact: Provides a practical, accessible prognostic metric with strong discrimination for short-term mortality and organ injury, supporting early risk stratification in the ICU.
Clinical Implications: LAR can be integrated into early triage and monitoring to identify high-risk patients, refine thresholds for escalation, and potentially guide adjunctive testing or therapies.
Key Findings
- LAR was an independent risk factor for septic shock, SA-AKI, and 28-day mortality in multivariable analyses.
- ROC AUCs: 0.705 for shock (cutoff 0.106), 0.762 for SA-AKI (cutoff 0.097), and 0.863 for 28-day mortality (cutoff 0.098).
- Risk of shock, SA-AKI, and death increased significantly across higher LAR quartiles.
- As a continuous variable, higher LAR remained associated with worse outcomes.
Methodological Strengths
- Prospective cohort design with predefined outcomes
- Multivariable logistic regression and ROC/AUC analyses with quartile stratification
Limitations
- Single-center study limits generalizability and lacks external validation
- Sample size and calibration/decision-curve analyses not reported in the abstract
Future Directions: Validate LAR thresholds in multicenter cohorts, compare against established scores, and assess additive value in clinical decision pathways and randomized triage strategies.
The aim of this study is to evaluate the prognostic value of the lactate to albumin ratio (LAR) in predicting morbidity, acute kidney injury associated with sepsis (SA-AKI) and mortality in sepsis patients. This was a single-center prospective cohort study. All adult patients above the age of 18 with a diagnosis of sepsis who presented between January 1, 2024, and June 1, 2025, were included. The primary outcome was 28-day mortality, septic shock and SA-AKI. The patients were divided into no