scholarly journals Peripheral Blood T Cell Gene Expression Responses to Exercise and HMB in Sarcopenia

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2313
Author(s):  
Suk-Ling Ma ◽  
Junyi Wu ◽  
Liuying Zhu ◽  
Ruth Chan ◽  
Amy Wang ◽  
...  

Background: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia. Methods: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone (n = 11), combined-exercise program and nutrition supplement (n = 23), and waitlist control group (n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests. Results: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups (p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes (RASGRP1, BIN1, LEF1, ANXA6, IL-7R, LRRN3, and PRKCQ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction. Conclusions: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Daniel Remondini ◽  
Nathan Intrator ◽  
Claudia Sala ◽  
Michela Pierini ◽  
Paolo Garagnani ◽  
...  

2009 ◽  
Vol 85 (3) ◽  
pp. 250-261 ◽  
Author(s):  
Daila S. Gridley ◽  
Michael J. Pecaut ◽  
Asma Rizvi ◽  
George B. Coutrakon ◽  
Xian Luo-Owen ◽  
...  

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S068-S069
Author(s):  
R Gonsky ◽  
P Fleshner ◽  
G Botwin ◽  
E Biener-Ramanujan ◽  
D McGovern ◽  
...  

Abstract Background CD is defined by transmural inflammation leading to inflammatory, stricturing and/or penetrating phenotypes. Identifying underlying molecular pathways and distinct disease subsets is critical for improved prognostics, therapeutics and biomarker discovery. Methods CD3+ T cells were purified from paired blood and mucosal tissue from 101 CD and 17 non-IBD subjects requiring surgery. Longitudinal samples (n = 30) were collected 4–13 mo. post-surgery. Expression profiles were generated by RNAseq, T-cell subset deconvolution by xCell and transcriptome-wide associations (TWAS) using TWAS-hub. Results Unsupervised clustering of peripheral T-cell gene expression at surgery revealed 2 CD profiles: Expression from cluster1, labelled CD-PBT (63%), clustered tightly with the non-IBD group. In cluster2, expression shifted from a peripheral toward a mucosal profile, labelled CD-PBmu(cosal) (37%). CD-PBmu was defined by differentially expressed genes (DEG) (1944 DEG, p &lt; 0.001) regulating cell migration and adhesion pathways and a distinct T-cell subset composition associated with stricturing disease (p = 0.03), increased resected bowel length (p = 0.036) and post-op recurrence (p = 0.01). There were no significant differences in disease location/behaviour. Independent validation (5 public datasets) confirmed the CD-PBmu signature in data from whole blood (CD patients failing anti-TNF therapy, n = 204) and the mucosal-like expression profile in data from ileal tissue (paediatric CD patients, studies n = 751). A defining feature of CD-PBmu, validated in a separate CD cohort (n = 19), was decreased pro-inflammatory cytokine/chemokine and adhesion molecule expression following surgery (900 DEG, p &lt; 0.001). No post-surgery change in expression was detected in CD-PBT. A 44-gene classifier was identified to enable clinical application. The classifier accurately detected the CD-PBmu patient subtype, correlated with the altered composition of peripheral T-cell subsets and overlapped with IBD associated TWAS signals (&gt;60%). Recently, another group posed a blood-based 17 gene panel as predictive for aggressive IBD. These genes were not predictive for either the CD-PBmu or CD-PBT subtype (&lt;50% DEG). Conclusion Severe CD can be stratified into 2 subtypes based on peripheral T-cell gene expression. Circulating T cells from CD-PBmu exhibit a mucosal-like gene signature, altered T-cell subset composition, clinical features of severity and decreased pro-inflammatory gene expression post-surgery. These findings hold potential to identify targets for CD subtype-specific therapeutic development. The 44-gene classifier overlapped with multiple paediatric CD datasets, suggesting the potential application of these findings for treatment stratification early in the disease process.


2020 ◽  
Vol 145 (2) ◽  
pp. AB89
Author(s):  
Kris Erickson ◽  
Jenna Bergerson ◽  
Kathryn Hulse ◽  
Kiwon Nam ◽  
hiam Abdala-Valencia ◽  
...  

2018 ◽  
Vol 19 (3) ◽  
pp. 291-301 ◽  
Author(s):  
David Zemmour ◽  
Rapolas Zilionis ◽  
Evgeny Kiner ◽  
Allon M. Klein ◽  
Diane Mathis ◽  
...  

2021 ◽  
pp. 108820
Author(s):  
Sara Anvari ◽  
Levi Watkin ◽  
Kimal Rajapakshe ◽  
Oluwatomi Hassan ◽  
Kimberly Schuster ◽  
...  

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