Late-onset neonatal sepsis: genetic differences by sex and involvement of the NOTCH pathway

Ciesielski, Timothy H.; Zhang, Xueyi; Tacconelli, Alessandra; Lutsar, Irja; Cabre, Vincent Meiffredy de; Roilides, Emmanuel; Ciccacci, Cinzia; Borgiani, Paola; Scott, William K.; Aboulker, Jean Pierre; Akbas, Oguz; Allegro, Antonella; Auriti, Cinzia; Benichou, A.; Bertaina, Chiara; Bilardi, Davide; Bonatti, Giulia; Canpolat, Fuat Emre; Carducci, Francesca Calò; Chazallon, Corine; Drazdienė, Nijole; Esposito, Susanna; Faggion, Silvia; Fournier, Isabelle; Germovsek, Eva; Giaquinto, Carlo; Gottardi, Giorgio; Grossele, Tiziana; Hallik, Maarja; Haass, Cristina; Heath, Paul R.; Huertas, Tatiana Múnera; Ierardi, Valentina; Ilmoja, Mari‐Liis; Iosifidis, Εlias; Kahi, Sandrine; Kanmaz, H. Gozde; Karagianni, Paraskevi; Katragkou, Aspasia; Kaur, Eve; ̈, Birgit Kiilaspa ̈a; Kipper, Karin; Kontou, Aggeliki; Kougia, Victoria; Kuznetsova, Jelena; Lolli, Elisabetta; Metsvaht, Tuuli; Meyer, Laurence; Mitsiakos, Georgıos; Montinaro, Valentina; Mosca, Fabio; Mylonas, Makis; Netzer, Emmanuelle; Oeser, Clarissa; Omeñaca, F; Pana, Zoi Dorothea; Paoloni, Maria Luisa; Perniciaro, S.; Picault, Laura; Pietrasanta, Carlo; Pugni, Lorenza; Ronchi, Andrea; Rossi, Paolo; Şahin, Suzan; Saïdi, Yacine; Sánchez, Laura; Sarafidis, Kosmas; Spinelli, Marina; Standing, Joseph F.; Tagliabue, Claudia; Tammekunn, Tuuli; Tiburzi, Nina; Trafojer, Ursula; Usonis, Vytautas; Warris, Adilia; Williams, Scott M.; Sirugo, Giorgio

doi:10.1038/s41390-022-02114-8

Cited by 8 publications

(2 citation statements)

References 58 publications

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“…It has been reported that there are differences in immune response to infection between women and men, such as the expression of pattern recognition receptors in innate immune response and the functional response of phagocytes and antigen presenting cells. [28][29][30] However, Cox multivariate regression and nomogram analysis showed that gender had no statistical significance in the prognosis of sepsis. PRKCQ-AS1 as an immune-related factor in the progression of sepsis, Pearson correlation analysis showed that PRKCQ-AS1 was related to gender (p=0.049), indicating that factor mediating factors may interfere with the regulation of sepsis by PRKCQ-AS1, such as sex hormones.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis

Ding,

Liang,

Xia

et al. 2024

JIR

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Background Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis. Methods Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan–Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit. Results Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress. Conclusion We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis

Ding,

Liang,

Xia

et al. 2024

JIR

View full text Add to dashboard Cite

show abstract

“…The summary data for neonatal sepsis was collected from the most updated GWAS of this disease which included 224 late-onset neonatal sepsis cases and 273 controls from six European countries ( 19 ). In this GWAS, late-onset neonatal sepsis was defined as sepsis presenting from 3 to 90 days of age, and the diagnosis was established by clinical criteria consensus guidelines.…”

Section: Methodsmentioning

confidence: 99%

Effect of neonatal and adult sepsis on inflammation-related diseases in multiple physiological systems: a Mendelian randomization study

Zhao

Tan

et al. 2023

Front. Endocrinol.

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BackgroundLong-term impact of sepsis on whole body systems is not well investigated. The aim of the study was to explore the potential association of neonatal/adult sepsis with several inflammation-related diseases in multiple physiological systems.MethodsInstrumental variables for neonatal and adult sepsis were collected from the public genome-wide association studies, which must satisfy the correlation, exclusivity and independence assumptions. Mendelian randomization methods (including random-effect inverse-variance weighted, MR-PRESSO, weighted median and MR-Egger) were used to determine the genetic association of neonatal/adult sepsis with asthma, allergy, rheumatoid arthritis, body mass index/obesity, type 1/type 2 diabetes and intelligence/dementia. Sensitivity analyses were conducted to assess heterogeneity and horizontal pleiotropy. The study was performed by TwoSampleMR in R software.ResultsThe inverse-variance weighted method reported that neonatal sepsis was related to the decreased level of body mass index (OR = 0.988, 95%CI = 0.980 ~ 0.997, P = 0.007), and adult sepsis was related to the decreased risk of obesity (OR = 0.785, 95%CI = 0.655 ~ 0.940, P = 0.009). These results were supported by the other Mendelian randomization methods. In addition, the study did not find any association of neonatal/adult sepsis with the other inflammation-related diseases. No heterogeneity and horizontal pleiotropy were found using sensitivity analyses.ConclusionSepsis had the potential to reduce the risk of obesity or body mass index level at a genetic level, both in neonates and in adults.

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The fetal response to maternal inflammation is dependent upon maternal IL-6 in a murine model

et al. 2023

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Late-onset neonatal sepsis: genetic differences by sex and involvement of the NOTCH pathway

Cited by 8 publications

References 58 publications

Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis

Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis

Effect of neonatal and adult sepsis on inflammation-related diseases in multiple physiological systems: a Mendelian randomization study

The fetal response to maternal inflammation is dependent upon maternal IL-6 in a murine model

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