Project description:Early-life sepsis remains one of the leading causes of global morbidity and mortality in the neonatal population, especially preterm infants. Using a preterm piglet model of neonatal sepsis to test nutritional interventions as a therapeutic approach, we demonstrated that high parenteral glucose induced hyperglycemia with severe sepsis, whereas glucose restriction offered protection against infection but led to severe hypoglycemia. Building on this, our current study aims to maintain normoglycemia through galactose metabolism or gluconeogenesis and reduce sepsis risks by substituting glucose with galactose, or supplementing glucogenic amino acids (GAAs).
2024-06-30 | GSE263512 | GEO
Project description:Vertical Transmission of GBS in The Gambia
Project description:DNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality due to the lack of sensitive diagnostic and prognostic biomarkers. Delay in sepsis diagnosis leads to treatment difficulties and poor outcomes. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. Illumina 450K methylation microarray revealed that the genes involved in transendothelial leukocyte migration were differentially methylated in septic newborns compared to non-septic newborns, especially the Protocadherin Beta group. Genes like ITGB2-AS1, CCS were found to be differentially methylated significantly, which gives the hope of developing novel, potential epigenetic markers for neonatal sepsis. From this study, we conclude that DNA methylation might play crucial functions in the pathophysiology of neonatal sepsis which was obvious from the difference in methylation level among septic and non-septic babies. In future, the potentiality of these epigenetic biomarkers can be studied in large scale with appropriate techniques which will give further in depth knowledge in this context.
Project description:DNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality due to the lack of sensitive diagnostic and prognostic biomarkers. Delay in sepsis diagnosis leads to treatment difficulties and poor outcomes. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. Illumina 450K methylation microarray revealed that the genes involved in transendothelial leukocyte migration were differentially methylated in septic newborns compared to non-septic newborns, especially the Protocadherin Beta group. Genes like ITGB2-AS1, CCS were found to be differentially methylated significantly, which gives the hope of developing novel, potential epigenetic markers for neonatal sepsis. From this study, we conclude that DNA methylation might play crucial functions in the pathophysiology of neonatal sepsis which was obvious from the difference in methylation level among septic and non-septic babies. In future, the potentiality of these epigenetic biomarkers can be studied in large scale with appropriate techniques which will give further in depth knowledge in this context. DNA methylation analysis of three septic newborns and three non-septic newborns were performed with Illumina Infinium HumanMethylation450 BeadChip. Peripheral venous blood sample was collected from the babies during the third day of birth while taking blood for routine investigations. Non-septic babies are babies admitted to NICU and sampled for other minor ailments. Genomic DNA was extracted using QIAmp DNA Blood Mini kit (Qiagen, Hilden, Germany) and bisulfite treated using EZ DNA methylation kit (Zymoresearch, USA).
Project description:Preterm infants are highly susceptible to late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) but specific biomarkers for diagnosis and effective treatment are lacking. Neutrophil extracellular traps (NETs) are related to sepsis in adults but not investigated in infant conditions. This is the first proteome study to document that circulating NETs are involved in neonatal LOS and NEC. cfDNA and NET proteins may provide new potential diagnostic markers for these diseases.
Project description:Introduction: Early life is characterized by heightened susceptibility to infections and is recognized as a major determinant of the immune system development and the overall health for the entire human lifespan. However, our knowledge of the development of the neonatal immune system is incomplete, limiting the development of novel preventative and therapeutic strategies, especially in newborns. To gain insight into the early immune system development and plasma proteome ontogeny, the Expanded Program on Immunization Consortium (EPIC) led by Professor Ofer Levy MD at Boston Children’s Hospital, Harvard Medical School and Tobias R. Kollmann Telethon Kids Institute, Australia as part of the Human Immunological Project Consortium (HIPC), established two independent cohorts of plasma from healthy newborns born by vaginal delivery during the first week of life. Methods: Blood samples were collected from 30 newborns in The Gambia (Medical Research Council Unit, The Gambia) at the day of birth (day of life, DOL 0) and at one of the follow-up visits on DOL1, DOL3, or DOL7. A similar validation cohort was collected in Papua New Guinea (PNG) (Institute for Medical Research, Papua New Guinea, Australasian) from 19 newborns. The plasma proteome was characterized by LC-MS on a Q Exactive using the proven and published plasma proteomics platform developed in the Steen Laboratory, led by Dr Hanno Steen, Director of Proteomics at Boston Children’s Hospital, Harvard Medical School, employing only microliter of plasma prepared in a 96-well plate format. The data was analyzed with MaxQuant. Results: We characterized 385 blood-plasma proteins. Utilizing the paired study design, we identified consistent changes related to ontogeny and cellular growth pathways in the blood-plasma proteome. Conclusion: This dataset allows for studying the early ontogeny of the plasma proteome, and in extension the early immune system development, in two independent healthy cohorts. Characterization of the plasma proteome may provide novel insight into new approaches to prevent, detect, and treat infectious diseases. Acknowledgements: We would like to thank all the participating families and all past and current members of the EPIC-HIPC, and the Steen Laboratory, without whom this study would not be possible. A special recognition goes to the teams who established the unique cohorts in The Gambia, by Professor Beate Kampmann and Dr Olubukola T. Idoko at The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia, and in PNG, by Anita H.J. van der Biggelaar and William S. Pomat at Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia Perth, Australia.
2020-11-24 | PXD019817 | Pride
Project description:Hospital Epidemiology Study, Neonatal Sepsis in the Ho Teaching Hospital, Ghana
Project description:Neonatal sepsis is an important health-care concern worldwide occurring more frequently in premature newborns and for which diagnosis is yet a challenge, causing delays in therapy and increasing the risk of death. DNA methylation, involved in regulating gene expression, has been associated with the development and progression of sepsis. Actually, the detection of differentially methylated regions (DMRs) is a promising epigenetic tool used for diagnosis and prognosis in complex diseases. The present study focuses on two different bioinformatic methods, DMRcate and mCSEA, with the aim of obtaining different methylation traits using Illumina Infinium Human Methylation EPIC data of neonatal sepsis patients. The DMR sets obtained by both approaches can also be overlapped to obtain a reliable set of DMRs which can contribute to improve our understanding on the molecular pathways underlying disease.
Project description:We aimed to identify the gene network and pathway biology associated with neonatal sepsis by determining genome-wide alterations in host RNA in infected infants Samples were obtained from control and infected human neonates.