Project description:Background: The effects of iron deficiency anemia (IDA) during infancy extend beyond the hematologic compartment and include short- and long-term adverse effects on many tissues including the brain. However, biomarkers of iron-dependent brain health are lacking in humans. Prior analyses in rhesus infants indicated abnormal serum and cerebral spinal fluid (CSF) multiomic profiles both prior to and during IDA, characterized by alterations suggestive of hepatic and brain metabolic dysfunction, and impaired energy metabolism. Objective: To determine whether serum and CSF biomarkers of iron deficiency (ID)-induced metabolic dysfunction are concordant in the pre/early anemic stage of ID in a nonhuman primate model of infantile IDA. Methods: Paired serum and CSF specimens were collected from iron-sufficient (IS; n = 12) and ID (n = 7) rhesus infants at 4-months (preanemic period) and 6-months (anemic period) of age. Hematological, metabolomic, and proteomic profiles were generated via HPLC/MS at both timepoints to discover serum biomarkers of ID-induced brain metabolic dysfunction. Results: We identified and quantified 227 metabolites and 205 proteins in serum. Abnormalities indicating altered liver function, lipid dysregulation, and increased acute phase proteins were present in ID. In CSF, we measured 210 metabolites and 1,560 proteins with ID infants displaying metabolomic and proteomic changes indicating disrupted synaptogenesis. Concurrent systemic and CSF proteomic and metabolomic changes were present in the preanemic and anemic periods. Conclusions: Multiomic serum and CSF profiling uncovered pathways disrupted by ID in both the preanemic and anemic stages of infantile IDA, including evidence for liver metabolic dysfunction and acute phase responses. Parallel changes observed in serum and CSF potentially provide measurable serum biomarkers that reflect at-risk brain processes early during ID.
Project description:Statin play an important role in the treatment of diabetic nephropathy (DN). In recent years, increasing attention has been given to the relationship between statin and insulin resistance, but many randomized controlled trial (RCT) studies confirm that the therapeutic effect of statin on DN is more beneficial than harmful. However, further confirmation of whether the beneficial effects of long-term statin administration on DN still outweigh the detrimental effects is needed. In the current study, we found that long-term statin administration may exacerbate insulin resistance, interfere with glucose and lipid metabolism, lead to renal cell apoptosis, inflammation and severe renal fibrosis, and ultimately decrease renal function. Mechanistically,Through RNA seq analysis, we found that long-term statin administration affects lipid metabolism and exacerbates inflammation and fibrosis.
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:The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans. This randomized, placebo-controlled, double-blind study had a 3-armed parallel design. Overweight/obese participants were randomized to oral intake of amoxicillin, vancomycin or placebo for 7 consecutive days. After an overnight fast, subcutaneous adipose tissue biopsies were taken that were subjected to gene expression profiling by array.
Project description:Pathological neovascularization (NV) can cause visual impairment in retinopathy of prematurity (ROP). Current treatments addressing vasoproliferative (Phase II) ROP are costly and can lead to severe complications. We show that well-timed topical 0.1% dexamethasone eye drops during early retinal neovascular formation prevents NV in five extremely preterm infants at high risk for ROP and in mouse oxygen-induced retinopathy (OIR) modeling ROP. In OIR mice, daily treatment before any NV has limited efficacy in mitigating NV, while treatment after peak NV exhibits no statistically significant effect but with a trend to exacerbating NV. Optimally timed topical dexamethasone suppression of NV in OIR is associated with increased retinal mitochondrial gene expression and a decrease in inflammatory markers predominantly expressed in immune cells. This study provides new insights into topical steroid effects in retinal NV and into mitochondrial function in phase II ROP, and suggests a simple approach to preventing severe ROP.
Project description:We conducted a randomized controlled clinical trial investigating the effects of resistance exercise therapy for incomplete SCI. We integrated the analysis of plasma proteomics to explore the molecular and cellular changes induced by resistance exercise.
2025-01-26 | PXD060193 |
Project description:A short-term, randomized, controlled, feasibility study of the effects of different vegetables on gut microbiota and microRNA expression in infants