Daily Sepsis Research Analysis
Three impactful sepsis-related studies span epidemiology, diagnostics, and mechanistic therapy. A WHO Bulletin meta-analysis quantifies the burden of pregnancy-associated acute kidney injury in LMICs with sepsis as a key etiology; a preclinical study shows EPC-derived exosomal miR-218 ameliorates sepsis-related acute lung injury via HMGA1-dependent macrophage polarization; and a clinical-mechanistic study identifies miR-186 as a diagnostic biomarker that modulates hyperinflammation in sepsis.
Summary
Three impactful sepsis-related studies span epidemiology, diagnostics, and mechanistic therapy. A WHO Bulletin meta-analysis quantifies the burden of pregnancy-associated acute kidney injury in LMICs with sepsis as a key etiology; a preclinical study shows EPC-derived exosomal miR-218 ameliorates sepsis-related acute lung injury via HMGA1-dependent macrophage polarization; and a clinical-mechanistic study identifies miR-186 as a diagnostic biomarker that modulates hyperinflammation in sepsis.
Research Themes
- Sepsis in maternal health: pregnancy-associated acute kidney injury in LMICs
- Exosome-mediated microRNA therapy for sepsis-related organ injury
- MicroRNA biomarkers for distinguishing sepsis from infection
Selected Articles
1. Incidence of pregnancy-associated acute kidney injury in low- and middle-income countries: a meta-analysis.
This meta-analysis across 40 studies (424,081 pregnancies) in LMICs found pregnancy-associated AKI occurs in 91 per 10,000 pregnancies, with highest incidence in the WHO African Region. It carries substantial maternal (OR 18.8 for death) and fetal risk, and sepsis accounts for 16.5% of etiologies alongside pre-eclampsia and hemorrhage.
Impact: Provides robust, policy-relevant quantification of pregnancy-associated AKI burden and etiologies in LMICs, highlighting sepsis as a major contributor and targets for preventive strategies.
Clinical Implications: Supports prioritizing antenatal care and targeted prevention (preeclampsia screening, hemorrhage control, infection prevention and early sepsis management) to reduce AKI-related maternal and fetal harms.
Key Findings
- Pooled incidence of pregnancy-associated AKI: 91 per 10,000 pregnancies (95% CI 63–133), highest in WHO African Region (254; 95% CI 152–421).
- Maternal case fatality 10.8% and neonatal death or stillbirth in 29.8% of cases.
- AKI associated with 18.8-fold higher odds of maternal death and 4.6-fold higher odds of adverse fetal outcomes; leading etiologies: pre-eclampsia (44.1%), hemorrhage (26.2%), sepsis (16.5%).
Methodological Strengths
- Systematic review and meta-analysis with large aggregated sample (424,081 pregnancies) across 15 countries.
- Use of KDIGO diagnostic criteria and exploration of heterogeneity via subgroup analyses and meta-regression.
Limitations
- Heterogeneity across studies and settings may affect pooled estimates.
- Predominantly observational data; residual confounding and reporting biases possible.
Future Directions: Prospective, standardized surveillance and intervention studies in LMICs to test targeted prevention (infection control, hypertensive disorder management, hemorrhage protocols) and reduce AKI burden.
OBJECTIVE: To conduct a systematic review and meta-analysis of pregnancy-associated acute kidney injury in low- and middle-income countries. METHOD: We searched the databases Cochrane Central Register of Controlled Trials, Embase, Google Scholar, OvidMedline, ProQuest and Scopus for articles published during 2013-2025 reporting the incidence, etiology and outcomes of the condition in low- and middle-income countries. We conducted a meta-analysis of the studies that used the diagnostic criteria of the Kidney Disease: Improving Global Outcomes organization. We conducted subgroup analyses and a meta-regression to explore sources of heterogeneity. FINDINGS: We reviewed 43 studies and included 40 in our meta-analysis, covering 424 081 pregnancies in 15 low- and middle-income countries. We observed a pooled incidence of 91 cases (95% confidence interval, CI: 63-133) per 10 000 pregnancies, highest in studies conducted in the World Health Organization African Region (254; 95% CI: 152-421). We estimated case fataliy of 10.8% (95% CI: 7.6-15.3) and neonatal death or stillbirth in 29.8% of cases (95% CI: 24.2-36.1). We observed that the condition was associated with 18.8-fold higher odds of maternal death (95% CI: 10.0-35.5) and 4.6-fold higher odds of adverse fetal outcomes (95% CI: 2.1-10.0). We identified pre-eclampsia (44.1%), haemorrhage (26.2%) and sepsis (16.5%) as the leading etiologies. CONCLUSION: Pregnancy-associated acute kidney injury is a significant maternal health concern in low- and middle-income countries. By providing more resources to prevent the common etiologies and expand the availability of antenatal care, its deleterious effects on maternal and fetal outcomes can be reduced.
2. Exosomal miR-218 secreted from endothelial progenitor cells mitigates acute lung injury in sepsis mice by inhibiting HMGA1 in alveolar macrophages.
EPC-derived exosomes deliver miR-218 to the lung, where it targets HMGA1 in alveolar macrophages, reducing M1 polarization and ameliorating sepsis-induced acute lung injury in mice. Gain/loss and rescue experiments substantiate HMGA1 as a functional target mediating the protective effect.
Impact: Demonstrates a mechanistic, exosome-based microRNA therapy that modulates innate immune polarization to protect against sepsis-induced lung injury, highlighting a translational pathway.
Clinical Implications: Suggests EPC-exosome miR-218 delivery as a candidate therapeutic to attenuate sepsis-related acute lung injury by reprogramming macrophage polarization; requires dose, safety, and efficacy testing in large animals and humans.
Key Findings
- EPC-derived exosomes accumulate in lungs and are taken up by alveolar macrophages; exosomal miR-218 reduces sepsis-induced acute lung injury in vivo.
- miR-218 suppresses LPS-induced M1 polarization of macrophages; inhibition enhances M1 polarization in vitro.
- HMGA1 is a direct target of miR-218; HMGA1 overexpression abrogates the protective effects, confirming pathway specificity.
Methodological Strengths
- Multi-level validation: in vivo exosome tracking and therapeutic effect, in vitro gain/loss of miR-218, and dual-luciferase target confirmation.
- Rescue experiments (si-/overexpression of HMGA1) to establish causal pathway.
Limitations
- Preclinical mouse model; human validation is lacking.
- Dosing, biodistribution kinetics, and off-target effects of exosome delivery were not comprehensively characterized.
Future Directions: Conduct large-animal studies to optimize exosome dosing and pharmacokinetics, and early-phase clinical trials to assess safety and biomarker-driven efficacy in sepsis-related lung injury.
BACKGROUND AND OBJECTIVE: Sepsis-related acute lung injury (S-ALI) had become an important public health issue worldwide. However, the mechanism of S-ALI was still not fully understood. This study aims to investigate the possibility of exosomes secreted from endothelial progenitor cells (EPCs) serving as a carrier for microRNA (miR)-218 to alleviate S-ALI and explore the possible mechanism. METHODS: Exosomes were isolated from EPCs of C57BL/6J mice using differential centrifugation. Exosomes tracking in vivo and their uptake by EPCs in vitro were detected. miR-218 inhibitor and mimic were applied to investigate its function in mice and regulating polarization of alveolar macrophages (AMs). Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-218. si-HMGA1 and oe-HMGA1 were used to investigate its function in regulating polarization of AMs. Rescue experiments were carried out to uncover the interaction between miR-218 and HMGA1 in AMs. RESULTS: Exosomes were isolated from EPCs and confirmed their accumulation in the mice lung as well as their uptake by AMs in vitro. In vivo, miR-218 transferred by exosomes secreted from EPCs mitigated ALI. In vitro, miR-218 inhibitor enhanced LPS-induced polarization of M1 macrophages, while miR-218 mimic suppressed these reactions. HMGA1 was confirmed as a target gene of miR-218, and its over-expression offset the protective effects of miR-218. CONCLUSIONS: miR-218 transferred by exosomes secreted from EPCs mitigated ALI in septic mice by inhibiting HMHA1 which regulates macrophages polarization. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-025-04558-1.
3. miR-186 Regulates Septic Hyperinflammation and Predicts Sepsis.
In a case-control cohort (20 sepsis vs 21 infection), circulating miR-186 was elevated in sepsis and outperformed procalcitonin and lactate for discrimination. Mechanistically, LPS induced miR-186; inhibiting miR-186 reduced key cytokines in HUVECs and in mice, indicating a regulatory role in septic hyperinflammation.
Impact: Proposes a microRNA with dual diagnostic and mechanistic relevance in sepsis, suggesting potential for additive biomarker panels and therapeutic modulation.
Clinical Implications: miR-186 could augment existing biomarkers to better distinguish sepsis from infection; therapeutic targeting of miR-186 pathways may attenuate hyperinflammation, pending validation in larger cohorts.
Key Findings
- Circulating miR-186 levels are significantly higher in sepsis than in infection and show better diagnostic performance than procalcitonin and lactate.
- LPS induces miR-186 in a dose-dependent manner; inhibition of miR-186 reduces IL-1β, IL-6, and IL-8 in HUVECs.
- In mice, miR-186 inhibition lowers IL-1β levels and NK cell ratios, indicating modulation of hyperinflammation.
Methodological Strengths
- Integrated clinical case-control analysis with in vitro and in vivo mechanistic validation.
- Comparative diagnostic assessment against standard biomarkers using ROC analyses.
Limitations
- Small, single-center retrospective cohort limits generalizability and precision of diagnostic estimates.
- Clinical outcomes and prospective validation were not assessed.
Future Directions: Prospective multicenter studies to validate diagnostic cutoffs and additive value to biomarker panels, and interventional studies to test miR-186 modulation in sepsis.
Sepsis is a life-threatening condition caused by infection-induced immune dysregulation. Clinically distinguishing sepsis from infection remains to be a challenge due to overlapping clinical features. Although miR-186 regulates cell proliferation and apoptosis, and was predicted to target immune-related genes, its role in sepsis is unclear. We retrospectively enrolled 21 infected patients and 20 sepsis patients. The miR-186 level in blood cells was detected using real-time PCR. Cytokine concentrations and lymphocyte subpopulation proportions were determined using flow cytometry. Clinical data were retrieved from medical records. The diagnostic ability of miR-186 was compared with procalcitonin and lactate using the receiver operating characteristic (ROC) curve. miR-186 was inhibited in human umbilical vein endothelial cells (HUVECs) and mice, followed by measurement of cytokine expression using real-time PCR and flow cytometry. The expression level of miR-186 was significantly higher in septic patients than in infected patients. miR-186 showed relatively better diagnostic performance for sepsis than procalcitonin and lactate. The in vitro assay showed that LPS enhanced miR-186 expression under a dose-dependent manner. In vitro miR-186 inhibition in HUVECs inhibited IL-1β, IL-6, and IL-8 expression. In vivo miR-186 inhibition significantly lowered IL-1β concentration and natural killer cell ratio. In this study, we found that miR-186 is significantly upregulated in sepsis and plays a regulatory role in cytokine expression, highlighting its potential as a diagnostic biomarker for sepsis.