Daily Sepsis Research Analysis

Dysregulation of macrophage autophagy plays a critical role in sepsis-induced acute lung injury (ALI); however, its underlying mechanism remains unclear. In this study, we aimed to identify the regulatory pathway involving the PIK3C3-MAPK14 signaling axis that drives ALI progression by controlling autophagy and macrophage polarization. Using machine learning transcriptomic analysis, MAPK14 was identified as a core gene associated with ALI, and multi-omics integration confirmed its upregulated expression in ALI tissues. MAPK14 localization to pro-inflammatory macrophages was determined using single-cell sequencing. Furthermore, we observed a significant positive correlation between MAPK14 and autophagy-related genes. Molecular docking and kinetic simulations revealed high-affinity interactions between PIK3C3 and MAPK14 (ΔG-bind = -127.722 ± 33.269 kJ/mol). In vitro experiments followed by Western Blot(WB) and RT-q polymerase chain reaction (PCR) assays demonstrated that lipopolysaccharide stimulation upregulated MAPK14 expression through downregulation of PIK3C3 expression, resulting in impaired autophagic flux (LC3-II/Ⅰ↓, TOM20↑, P62↑, HSP60↑). Flow cytometry and enzyme-linked immunosorbent assay (ELISA) confirmed a shift toward pro-inflammatory (M1) macrophage polarization. RNA pull-down assay directly captured the PIK3C3-MAPK14 complex, and functional validation showed that PIK3C3 overexpression significantly inhibited MAPK14 protein expression, whereas PIK3C3 knockdown enhanced it. In conclusion, targeting the PIK3C3-MAPK14 axis is a promising therapeutic strategy for ALI.

BACKGROUND: A hyperdynamic left ventricle (ejection fraction (EF) ≥70 %) on stress imaging is closely linked to diastolic dysfunction and may indicate heart failure with preserved EF (HFpEF) in the right clinical context. OBJECTIVES: To investigate the underlying causes and prognostic implications of hyperdynamic left ventricular ejection fraction (HDLVEF) in critically ill patients diagnosed with sepsis. METHODS: A total of 235 patients diagnosed with septic shock and admitted to the intensive care unit were included in this study. Diagnosis of sepsis was established based on the sequential organ failure assessment (SOFA) score, which was calculated upon admission and updated every 24 h using the worst values from the prior day. Transthoracic echocardiography (TTE) was performed either by the principal investigator or a certified cardiologist accredited by the Egyptian Medical Society of Echocardiography (EMSE). RESULTS: Among the 235 patients, 88 (37.4 %) died within 28 days, while 147 (62.6 %) survived. Hyperdynamic EF was significantly more prevalent in the deceased group compared to survivors, with an odds ratio of 4.822 (95 % CI: 1.467-8.852), indicating a strong association with mortality. Multivariate analysis identified several independent predictors of mortality, including older age, lower mean arterial pressure, higher SOFA scores, and elevated serum lactate levels. Additionally, the mortality rate was significantly higher among male patients. CONCLUSION: HDLVEF holds significant prognostic value in patients with sepsis in critical care. It may serve as a valuable early echocardiographic marker of sepsis-induced cardiomyopathy or cardiovascular dysfunction, potentially aiding in risk assessment and early therapeutic decisions. TRIAL REGISTRATION: The trial was registered before patient enrolment at ClinicalTrials.gov (ID/ NCT06993948).

INTRODUCTION: Despite advances in surveillance, protocolized resuscitation, and critical care organ support, sepsis remains a common and fatal complication in trauma. Trauma-induced systemic inflammatory response syndrome (SIRS) can mask the occurrence of sepsis, complicating the diagnosis of sepsis. Thus, it is significant to identify high-risk patients of sepsis among trauma-induced SIRS for early prevention, early diagnosis, and early intervention of sepsis. This study seeks to identify predictive biomarkers for sepsis in patients with trauma-induced SIRS. MATERIALS AND METHODS: The existing plasma proteomics data from 62 severe trauma patients with (38 cases) and without (24 cases) SIRS were retrospectively analyzed. Among the 38 patients with SIRS, 15 SIRS patients who subsequently developed sepsis (SDS) were assigned to SDS group, while the remaining 23 SIRS patients who did not develop sepsis (SDDS) constituted SDDS group. By comparing the SDS and SDDS groups, predictive biomarkers for sepsis in trauma-induced SIRS were identified. RESULTS: Fifteen differentially expressed proteins were identified between SDS and SDDS groups. We screened top 5 differentially expressed proteins as predictive biomarkers for sepsis in trauma-induced SIRS, including ANXA6 (area under the curve [AUC] = 0.881), FA12 (AUC = 0.873), TRY2 (AUC = 0.868), FIBG (AUC = 0.759), and DOPD (AUC = 0.745). The combined predictive performance of these biomarkers is better (AUC = 0.9913). To balance robust predictive performance with a minimal panel size, we developed a panel consisting of ANXA6 and FIBG, which demonstrated superior predictive performance (AUC = 0.9652). CONCLUSIONS: This study identified predictive biomarkers for sepsis in trauma-induced SIRS. Notably, integrating coagulation and inflammatory markers enabled substantial reduction in the number of required modeling indicators while preserving superior diagnostic performance. These findings offer new insights into developing early predictive panels.