P38 MAPK (mitogen-activated protein kinase) is a critical regulator in lung inflammation. It can be inactivated by DUSP1 (dual-specificity phosphatase 1) which was identified as a putative target of miR-429. miR-429 mimics directly targeted to the 3′-UTR of the gene encoding DUSP1 may result in the translational attenuation of DUSP1. Moreover, the phosphorylation of p38 MAPK was prolonged after miR-429 mimic treatment. Additionally, miR-429 expression was sensitive to LPS (lipopolysaccharide) stimulation and the miR-429 mimics increased the production of pro-inflammatory cytokines. However, anti-miR-429 reduced the LPS-induced production of pro-inflammatory cytokines. These results provide direct evidence that miR-429 is involved in the LPS-induced inflammatory response. In parallel with miR-429, miR-200b and miR-200c, but not miR-200a or miR-141, shared similar effects. In vivo, LPS induced the expression of miR-429, miR-200b and miR-200c in lung. At the same time, inhibiting these miRNAs by anti-miRNAs attenuated the LPS-induced pulmonary inflammatory response and injury. These findings reveal that miR-429 possesses pro-inflammatory activities and may be a potential therapy target for LPS-induced lung injury.

Background: Diabetes mellitus (DM) is relatively common among patients with sepsis, yet its precise impact on mortality risk remains unclear. This study aims to explore the relationship between DM and mortality risk in sepsis patients by synthesizing existing data, thereby providing evidence for clinical management. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane Library databases from their inception to October 20, 2025, identified observational studies evaluating the association between DM and mortality in patients with sepsis. A random-effects model was used to pool relative risks (RR) and 95% confidence intervals (CI) to assess the relationship between DM and sepsis-related mortality risk. Sources of heterogeneity were explored through sensitivity and subgroup analyses, and publication bias was assessed using the Egger test. Results: A total of 13 studies ( n = 1,209,263) were included in the analysis. The results of the meta-analysis indicate that DM is associated with an increased risk of mortality in sepsis patients [RR = 1.25, 95% CI (1.14, 1.38)]. Subgroup analyses revealed that DM is linked to a higher risk of in-hospital mortality [RR = 1.60, 95% CI (1.11, 2.31)], with stronger associations observed in specific regions and study designs. Notably, studies conducted in China [RR = 1.79, 95% CI (1.19, 2.70)], the Netherlands [RR = 1.14, 95% CI (1.12, 1.17)], and Israel [RR = 1.81, 95% CI (1.55, 2.12)], as well as cohort studies [RR = 1.25, 95% CI (1.13, 1.38)], showed more pronounced effects. Additionally, analyses based on the Sepsis-3 criteria also demonstrated a significant association between DM and increased mortality risk [RR = 1.59, 95% CI (1.24, 2.04)]. Conclusion: This meta-analysis indicates that DM is significantly associated with an increased risk of mortality in patients with sepsis, particularly with respect to in-hospital mortality. The observed association may be partially explained by DM-related pathophysiological mechanisms, such as immune dysfunction, dysregulated inflammatory responses, and the presence of chronic comorbidities. Subgroup analyses suggest that the strength of this association varies according to country, study design, and sepsis diagnostic criteria, underscoring the heterogeneity across existing studies. Systematic review registration: Registered with Prospero with registration number CRD420261279012.