Usefulness of Balanced High Protein Supplementation on Recovery and Clinical Outcomes After Chemotherapy
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ABSTRACT:
DISEASE(S): Colorectal Neoplasms
PROVIDER: 65981 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Rationale: Steroids are the mainstay of asthma therapy. However, it is unclear whether the benefits of steroids in asthma are merely based on anti-inflammatory properties. Steroids may also alter gene expression of airway smooth muscle (ASM). Hypothesis and Aims: We hypothesized that the transcriptomic profile of the ASM layer in endobronchial biopsies of atopic asthma patients changes by oral steroid therapy. First, we examined the change in ASM transcriptomic profile in endobronchial biopsies after 14 days of oral steroid therapy. Second, we investigated the association between changes in ASM transcriptomic profile and airway function. Methods: 12 atopic steroid-free asthma patients were included in this double-blind intervention study. Endobronchial biopsies were taken before and after 14 days of oral prednisolon (n=6) or placebo (n=6). RNA of laser-dissected ASM was sequenced (RNA-Seq) using the GS FLX+ System (454/Roche). Gene networks were identified using Ingenuity Pathway Analysis. RNA-Seq reads were assumed to follow a negative binomial distribution. At the current sample size the estimated false discovery rate was approximately 3%. Results: 15 genes were significantly changed by 14 days of oral prednisolon. 2 of these genes (FAM129A, SYNPO2) were associated with the methacholine PC20 (r=0.637, p=0.035; r=0.662, p=0.027). Pathway analysis revealed 3 gene networks that were associated with cellular functions including cellular growth, proliferation, and development. Conclusion: Oral prednisolon changes the gene expression profile of the ASM layer in asthma. This indicates that steroids also exert effects on the transcriptomic level of ASM in addition to their anti-inflammatory properties, which can promote improved airway function. The current randomized, double-blind, parallel, placebo-controlled intervention study comprised 4 visits. At visit 1, asthma patients were screened according to the in- and exclusion criteria prior to enrollment. Additionally, spirometry and methacholine bronchoprovocation test were performed. At visit 2, FEV1 reversibility was measured and endobronchial biopsies were collected during a bronchoscopy. Asthma patients were then prescribed oral prednisolon at a dose of 0.5 mg/kg per day or placebo for 14 consecutive days. The dosage and dosing scheme was based on international recommendations for the treatment of acute exacerbations [1]. On the 11th day after visit 2, the patients visited the lung function laboratory for spirometry and methacholine bronchoprovocation test. Finally, at visit 4 (15th day after visit 2) FEV1 reversibility was measured and endobronchial biopsies were collected by bronchoscopy. Airway smooth muscle was collected from the biopsies by laser capture microdissection and total RNA isolated. cDNA was prepared using the Ovation RNA-Seq System (NuGEN). RNA-Seq was performed using the GS FLX+ instrument (454/Roche). Sequence reads were mapped against the human genome (hg19; UCSC). Comparison of the numbers of reads per gene between the prednisolon and placebo study group was carried out with the R package DESeq.
2013-05-15 | E-GEOD-40996 | biostudies-arrayexpress
Project description:Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults. A double-blind placebo controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group (n=12) and the calcifediol group (n=10, 10 µg per day). Muscle biopsies were obtained before and after six months of calcifediol or placebo supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays. Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies. Calcifediol supplementation led to a significant increase in blood 25-hydroxycholecalciferol levels compared to the placebo group. No difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak. Correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any sensible cut-offs. P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups. Calcifediol supplementation did not affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults.
2019-06-10 | GSE123993 | GEO
Project description:Many chronic cutaneous diseases associated with microbial antigens demonstrate clinical progression due to T cell hyporesponsiveness. Appropriate antimicrobial therapy restores T cell function, leading to clinical resolution. Due to the association of sarcoidosis with mycobacterial antigens, we compared the efficacy of antimycobacterial therapy with placebo in chronic cutaneous sarcoidosis. We conducted a randomized, placebo-controlled, single-blind trial on chronic cutaneous sarcoidosis subjects. Participants received the oral CLEAR regimen: Levofloxacin 750 mg on day 1, then 500 mg daily, Ethambutol 1200 mg daily, Azithromycin 500 mg on day 1, then 250 mg daily, and Rifampin 300 mg daily, or a comparative placebo regimen, for a total of 8 weeks, with a 180 day follow-up. Participants were monitored for absolute change in lesion diameter and decrease in granulomas burden upon completion of therapy.
2013-07-23 | E-GEOD-39606 | biostudies-arrayexpress
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).
2011-06-01 | GSE27140 | GEO
Project description:The obese, insulin resistant state is characterized by impairments in lipid metabolism. Dietary polyphenols might improve these deteriorations. We have previously shown that 3-days supplementation of combined Epigallocatechin-gallate and Resveratrol (E+R) increased energy expenditure, which was accompanied by improved metabolic flexibility after a high-fat mixed-meal (HFMM) in men. The present study aimed to investigate whether these short-term effects translate into longer-term improvement of insulin sensitivity and lipid metabolism. In this randomized, double-blind study, 42 overweight subjects (21 male, 38±2 yrs, BMI 29.7±0.5 kg/m2, HOMA-IR 2.1±0.2) received either E+R (300 and 80 mg/d, respectively) or placebo (PLA) for 12 weeks (3 months). Before (t0) and after (t3) intervention, tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with stable isotope infusion. Fasting and postprandial (HFMM) lipid metabolism was assessed using indirect calorimetry and blood sampling. Adipose tissue and skeletal muscle lipolysis was measured using microdialysis in men and skeletal muscle biopsies were collected to assess mitochondrial function and gene expression alterations via microarray analysis. E+R supplementation increased fasting (P=0.06) and postprandial (P=0.03) fat oxidation but did not alter energy expenditure compared to PLA. This was accompanied by an E+R-induced increase in oxidative capacity in permeabilized muscle fibers (p<0.05). Moreover, E+R supplementation attenuated the increase in plasma triacylglycerol concentration that was observed in the PLA group (AUC, p<0.05), and tended to decrease visceral fat mass (P=0.09). Finally, insulin-stimulated glucose disposal and suppression of endogenous glucose production were not affected by E+R supplementation. 12 weeks E+R supplementation increased whole-body fat oxidation and skeletal muscle oxidative capacity, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects. To identify pathways that may underlie the E+R-induced improvement of skeletal muscle mitochondrial capacity, we performed microarray analysis on skeletal muscle biopsies (vastus lateralis muscle), collected before and after 12-weeks E+R or PLA treatment. Gene Set Enrichment Analysis (GSEA) indicated that the most upregulated pathways after E+R supplementation were related to the citric acid cycle and respiratory electron transport chain, while pathways related to carbohydrate metabolism were upregulated in the PLA group. In this randomized, double-blind placebo-controlled, parallel intervention trial, subjects received either a combination of E+R supplements (INTV, 282 mg/d and 80 mg/d, respectively) or placebo (PLA, partly hydrolyzed microcrystalline cellulose-filled capsules) for a period of 12 weeks (3 months) to assess effects of E+R supplementation on tissue-specific insulin sensitivity (primary outcomes) and fasting and postprandial substrate metabolism (secondary outcomes). Skeletal muscle (m. vastus lateralis) biopsies were taken under local anesthesia during fasting conditions before (t0) and after the 12-weeks (t3) intervention period. Extraxted RNA was hybridized on HTA 2.0 Affymetrix arrays and microarray analysis was performed on paired sample sets for 27 subjects (p, PLA n = 14; E+R n = 13).
2016-08-03 | E-GEOD-71614 | biostudies-arrayexpress
Project description:We present the biopsy sub-study results from the first randomized, placebo-controlled clinical trial in patients with alopecia areata (AA) with ≥50% scalp hair loss and ≤7 years since the last AA episode. In this sub-study, we evaluated the molecular responses to PF-06651600, an oral inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, and PF-06700841, an oral TYK2/JAK1 inhibitor, versus placebo in nonlesional and lesional scalp biopsies of biopsy samples from patients with AA.
2022-01-25 | GSE148346 | GEO
Project description:Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of the study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg EGCG from green tea extract, 220 mg EPA and 180 mg DHA from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 ug folic acid) would reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Women were assigned using a randomized double-blinded placebo-controlled trial to Q-Mix or placebo groups. Overnight fasted blood samples were collected and subjected to RNA expression analysis on Affymetrix Hugene ST1_1 arrays. Randomized, double-blinded, placebo controlled study.Subjects were randomized to either mixed flavonoid-fish oil supplement group (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg EGCG from green tea extract, 400 mg n3-PUFAs (220 mg EPA and 180 mg DHA) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) or placebo (n=29 samples, including pre- and post-treatment samples in the Q-Mix and placebo arms).The placebo did not contain quercetin, vitamin C, and niacin. Subjects were instructed to ingest two soft chew supplements twice daily (upon awakening, and between 6:00-7:00 pm) for 70 days. A three-day food record was used to assess typical energy and nutrient intake. No restrictions were placed on diet, supplement usage or medications with the exception that subjects agreed to avoid any non-steroidal anti-inflammatory drugs and dietary supplements that influence inflammation or oxidative stress.
2015-11-02 | E-GEOD-74560 | biostudies-arrayexpress
Project description:Nicotinamide riboside supplements (NRS) have been touted as a nutraceutical that promotes cardiometabolic and musculoskeletal health by enhancing nicotinamide adenine dinucleotide (NAD+) biosynthesis, mitochondrial function and/or the activities of NAD-dependent sirtuin deacetylase enzymes. This investigation examined the impact of NRS on whole body energy homeostasis, skeletal muscle mitochondrial function, and corresponding shifts in the acetyl-lysine proteome, in the context of diet-induced obesity using C57BL/6NJ mice. The study also included a genetically-modified mouse model that imposes greater demand on sirtuin flux and associated NAD+ consumption, specifically within muscle tissues. In general, whole body glucose control was modestly improved by NRS when administered at the midpoint of a chronic high fat diet, but not when given as a preventative therapy upon initiation of the diet. Contrary to anticipated outcomes, the study produced little evidence that NRS increases tissue NAD+ levels, augments mitochondrial function and/or mitigates diet-induced hyperacetylation of the skeletal muscle proteome.
2022-02-17 | PXD027904 | Pride
Project description:The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The purpose of the study was to detect the sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, resistance exercise. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4h post-exercise) or late recovery (24h post-exercise) time point. Muscle transcription profiles were compared in the resting state between men (n=6) and women (n=8), and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4h post-exercise, n=3 males, n=4 females; 24h post-exercise, n=3 males, n=4 females). A logistic regression-based method (LRpath), following Bayesian moderated t-statistic (IMBT), was used to test gene functional groups and biological pathways enriched with differentially expressed genes.
2010-12-06 | E-GEOD-24235 | biostudies-arrayexpress
Project description:Evidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. Animal studies and human epidemiological studies have implicated epigenetic modifications as playing a key role in this process, but there are limited data from large well-controlled human intervention trials. This study utilised a large double-blind randomized placebo-controlled trial to test whether a defined nutritional exposure in utero, in this case docosahexaenoic acid (DHA), could alter the infant epigenome. Pregnant mothers consumed DHA-rich fish oil (800 mg DHA/d) or placebo supplements from 20 weeks’ gestation to delivery. Blood spots were collected from the children at birth (n=991) and blood leukocytes at 5 years (n=667). Global DNA methylation was measured in all samples and Illumina HumanMethylation450K BeadChip arrays were used for genome-wide methylation profiling in a subset of 369 children at birth and 65 children at 5 years. There were no differences in global DNA methylation levels between the DHA and control group either at birth or at 5 years, but we identified 21 differentially methylated regions (DMRs) at birth, showing small DNA methylation differences (<5%) between the treatment groups, some of which seemed to persist until 5 years. The number of DMRs at birth was greater in males (127 DMRs) and in females (72 DMRs) separately, indicating a gender-specific effect. In conclusion, maternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. While the potential functional significance of these changes remains to be determined, these findings further support the role of epigenetic modifications in developmental programming in humans, and points the way for future studies.
2018-02-06 | GSE89278 | GEO