Project description:Peritoneal dialysis (PD) is a modality of renal replacement therapy in which the high volumes of available PD effluent (PDE) represents a rich source of biomarkers for monitoring disease and therapy. Although this information could help guiding the management of PD patients, little is known about the potential of PDE to define pathomechanism-associated molecular signatures in PD. Here we use a high-performance multiplex proteomics approach based on depletion of highly abundant plasma proteins and enrichment of low abundance proteins for PDE samples from PD patients of a phase 2 randomized clinical trial, who received either standard PD fluid or a novel PD fluid (added alanyl-glutamine (AlaGln)) in an open-label, randomized, single-center, cross-over clinical trial.
Project description:Asthma is multi-factorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics has shown anti-inflammatory effect and could regulate the gut-lung axis. Thus, a three-month randomized, double-blind, and placebo-controlled human trial was performed to investigate the adjunctive efficacy of probiotics in managing asthma.
Project description:Objective: The study aimed to characterize circulating immune cell subpopulation gene expression in human milk-fed (HMF) compared to cow's milk formula-fed (FF) infants using single-cell transcriptomics. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy HMF (n=6), and FF (n=3) infants who were 3 to 3.5 months old and enrolled in a non-randomized clinical trial. Single-cell RNA sequencing (scRNA-seq) was used to generate a PBMC atlas and evaluate gene expression in immune cell subsets. Differential expression analysis was performed on each cell type independently after clustering the cells by similar marker gene expression using the scGEAToolbox. Differentially expressed genes (DEGs) were subjected to pathway analyses using an online functional enrichment analysis program. Results: The relative abundance (%) of T and B lymphocytes, natural killer (NK) cells, and plasmacytoid dendritic cells were similar, while monocytes were higher in FF infants than in HMF infants (22.6 ± 10.7 vs 8.3 ± 5.6; P = 0.0314). In addition, innate and adaptive immune cells from FF infants exhibited a higher activation state compared to HMF infants. We identified 16 distinct cell subsets from the major immune cell types: three monocyte subsets, four NK subsets, two B cell subsets, and seven T cell subsets. Transcriptional profiles of each peripheral innate and adaptive immune cell subtype varied between HMF and FF infants. Pathway enrichment analysis of cell-specific transcriptional changes within subsets of major cell types revealed that the interleukin (IL)-4/IL-13 signaling pathways were upregulated in FF infants relative to HMF infants. Conclusion: These findings suggest that human milk downregulates peripheral immune cell cytokine transcriptional signatures linked to allergic inflammation and infection relative to formula feeding.
Project description:<p>Synbiotics may modulate gut microbiota and prevent infections. In a randomized controlled trial (NCT01625273) infants weaned from breast milk were fed formula with prebiotics (fructo- and galactooligosaccharides) or the same prebiotic formula with <em>Lactobacillus paracasei ssp. paracasei</em> strain F19 (synbiotics) from 1 until 6 months of age. The objective was to examine synbiotic effects on gut microbiota maturation. Fecal samples collected at ages 1, 4, 6 and 12 months (324 samples for microbial and 197 samples for metabolic characterization) were analyzed. We demonstrate enrichment of Bifidobacterium and increases in antimicrobial metabolites derived from microbial fermentation of phenylalanine and pectins in the synbiotic group. The gut microbiota of infants with lower respiratory tract infections (LRTI) were depleted of Lactobacillales but enriched in Klebsiella species and associated antimicrobial resistance genes. These compositional and functional changes of the gut microbiota may be linked to the previously reported reduction of LRTI in the synbiotic group.</p>
Project description:A genome-wide RNA expression study based on a Phase II randomized placebo-controlled clinical trial of topiramate (TPM) treatment of methamphetamine (METH) dependence. Gene expression data were analyzed based on TPM responses at Weeks 8 and 12, to identify differentially expressed genes and related pathways.
Project description:Obesity and overweight are closely related to diet, and gut microbiota play an important role in body weight and human health. The aim of this study was to explore how Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 supplementation alleviate obesity by modulating the human gut microbiome. A randomized, double-blind, placebo-controlled study was conducted on 72 overweight individuals. Over a 12-week period, probiotic groups consumed 5×10^9 colony-forming units of HY7601 and KY1032), whereas the placebo group consumed the same product without probiotics. After treatment, the probiotic group displayed a reduction in body weight (p <0.001), visceral fat mass (p <0.025), and waist circumference (p <0.007), and an increase in adiponectin (p <0.046), compared with the placebo group. Additionally, HY7601 and KY1032 supplementation modulated bacterial gut microbiota characteristics and beta diversity by increasing Bifidobacteriaceae and Akkermansiaceae, and decreasing Prevotellaceae and Selenomonadaceae. In summary, HY7601 and KY1032 probiotics exert anti-obesity effects by regulating the gut microbiota; hence, they have therapeutic potential for preventing or alleviating obesity and overweight.
Project description:Animal and epidemiological studies suggest that lycopene and fish oil may modify the risk or delay progression of prostate cancer, however, the molecular mechanisms involved are poorly understood. We examined the effects of these micronutrients on prostate gene expression in a double-blind placebo-controlled randomized clinical trial (Molecular Effects of Nutritional Supplements, MENS).
Project description:We profiled genome-wide gene expression in nasal scrapes following grass pollen challenge and Prednisone treatment. It was a randomized, double-blind, placebo-controlled, three-period, cross-over trial to evaluate the effects of single oral doses of 10 mg and 25 mg of prednisone on inflammatory mediators measured in nasal exudates after nasal allergen challenge in susceptible individuals with allergic rhinitis. It examined the ability to quantify responses to allergen challenge and resolve dose responsive treatment effects of prednisone.
Project description:In this open-label randomized controlled phase I/II trial, 20 stable peritoneal dialysis patients underwent two 4 h dwells with acidic glucose-based PDF, with and without 8 mM alanyl-glutamine (AlaGln) in a cross-over design. Unsupervised hierarchical clustering of transcriptomics data suggested specific effects of AlaGln in patients who had previously suffered from peritonitis.
