Project description:To investigate early blood biomarkers of BPD development, RNA from cord blood cells or peripheral blood cells of premature infants was subjected to RNA sequencing (RNA-Seq) and data were analyzed with 9 covariates including gestational age (GA), sex, birth weight (BW), estimated CD4+T cell%, CD8+T cell%, B cell%, monocyte%, granulocyte%, and nucleated red blood cell (NRBC)%. The effect of prolonged oxygen (>14 days O2) treatment in newborn intensive care unit on blood cell transcriptome was determined among nonBPD preterm infants.
Project description:Periventricular white matter damage (PWMD) is the principal pathological type of brain damage in premature. It causes irreversible damage to the overall function of the central nervous system resulting in cerebral palsy, convulsions, epilepsy, cognitive, motor dysfunction and other late effects. CircRNAs are participate in the biological processes underlying many nervous system diseases. However, the circRNA expression profile of peripheral venous blood of premature infants with PWMD is not completely understood. Three premature with white matter damage (PWMD group) and three infants without brain injury (Normal group) were enrolled. Peripheral venous blood was collected from both groups for extraction of RNA and circRNA sequencing was performed. The RNA-seq technique was used to screen the differentially expressed circRNA in peripheral blood of infants with PWMD. The accuracy of sequencing results was verified by quantitative reverse transcription polymerase chain reaction (q-PCR) to the differentially express partial circRNA in the sequencing results. Bioinformatics analysis of Host genes was performed with differential circRNA. TargetScan and Miranda were used to predict circRNA-binding miRNAs and mapped into a circRNA-miRNA co-expression network. There were 119 significantly different circRNAs as compared with premature without brain injury, along with 1 circRNA was up-regulated and 4 circRNAs were down-regulated expression in the PWMD group. Combined with the existing research results and bioinformatics analysis results after sequencing, it is suggested that circRNA may regulate the occurrence and development of white matter damage in premature infants by interacting with miRNA. This first study of its kind further identified the expression profile of circRNA in peripheral blood of premature with WMD, and provide a novel targets for further investigation about the molecular mechanisms underlying PWMD and potential therapeutic intervention.
Project description:<p class='ql-align-justify'>The gut microbiome has been associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigated the longitudinal fecal and plasma metabolome of 51 extremely premature infants using LC-HRMS-based untargeted metabolomics. This was expanded by an investigation of bile acids and amidated bile acid conjugates in feces and plasma by LC-MS/MS-based targeted metabolomics. The resulting data was integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor and T-cell profiles. We identified an early onset of differentiation in neuroactive metabolites and bile acids between infants with and without brain injury. We detected several bacterially-derived bile acid amino acid conjugates and secondary bile acids in the plasma already 3 days after delivery, indicating the early establishment of a metabolically active gut microbiome. These results give new insights into the early life metabolome of extremely premature infants.</p>
Project description:While preventing vertical HIV transmission has been very successful, the increasing number of HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). Immune developmental differences between iHEU and iHUU remains poorly understood and here we present a longitudinal multimodal analysis of infant immune ontogeny that highlights the impact of HIV/ARV exposure. Using mass cytometry, we show alterations and differences in the emergence of NK cell populations and T cell memory differentiation between iHEU and iHUU. Specific NK cells observed at birth were also predictive of acellular pertussis and rotavirus vaccine-induced IgG and IgA responses, respectively, at 3 and 9 months of life. T cell receptor Vβ clonotypic diversity was significantly and persistently lower in iHEU preceding the expansion of T cell memory. Our findings show that HIV/ARV exposure disrupts innate and adaptive immunity from birth which may underlie relative vulnerability to infections.
Project description:A prospective study for investigating the T-cell receptor (TCR) repertoire in T-cell mediated rejection (TCMR) after kidney transplantation. The pre-formed donor-reactive TCR repertoire was tracked in blood and tissue of patients after kidney transplantation and characteristics of TCR repertoires from patients experiencing a rejection were compared to patients with no histopathological signs of rejection.
Project description:Emerging evidence suggests that an increased density of pre-treatment CD8+ tumor-infiltrating lymphocytes (TILs) is associated with good response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. However, the significance of T-cell complexity in the clinical setting remains unknown. High-throughput T-cell receptor (TCR) β sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Changes in TCR repertoire before and after CRT were also analysed in 23 patients.