A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome

Misselbeck, Karla; Parolo, Silvia; Lorenzini, Francesca; Savoca, Valeria; Leonardelli, Lorena; Bora, Pranami; Morine, Melissa J.; Mione, Maria Caterina; Domenici, Enrico; Priami, Corrado

doi:10.1038/s41467-019-13208-z

Cited by 60 publications

(62 citation statements)

References 71 publications

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“…Nordihydroguaiaretic acid and phloretin have been confirmed to prevent high-fat-diet-induced metabolic dysfunction in mice. The efficacy of ibrutinib in lowering adipose inflammatory responses was shown in zebrafish studies [ 81 ]. Quercetin shows its anti-inflammatory, anti-obesity, and anti-diabetic effects in human and animal studies [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative analyses of biomarkers and pathways for adipose tissue after bariatric surgery

et al. 2020

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We explored potential biomarkers and molecular mechanisms regarding multiple benefits after bariatric surgery. Differentially expressed genes (DEGs) for subcutaneous adipose tissue (AT) after bariatric surgery were identified by analyzing two expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs and gene-TFs networks were interrogated to identify hub genes and associated pathways. Co-expressed DEGs included one that was up-regulated and 22 that were down-regulated genes. The enrichment analyses indicated that down-regulated DEGs were significantly involved in inflammatory responses. GSEA provided comprehensive evidence that most genes enriched in pro-inflammation pathways, while gene-sets after surgery enriched in metabolism. We identified nine hub genes in the PPI network, most of which were validated as highly expressed and hypomethylated in obesity by Attie Lab Diabetes and DiseaseMeth databases, respectively. DGIdb was also applied to predict potential therapeutic agents that might reverse abnormally high hub gene expression. Bariatric surgery induces a significant shift from an obese pro-inflammatory state to an anti-inflammatory state, with improvement in adipocyte metabolic function-representing key mechanisms whereby AT function improves after bariatric surgery. Our study deepens a mechanistic understanding of the benefits of bariatric surgery and provides potential biomarkers or treatment targets for further research.

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Section: Discussionmentioning

confidence: 99%

Integrative analyses of biomarkers and pathways for adipose tissue after bariatric surgery

et al. 2020

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“…Furthermore, it could be a powerful instrument to link pharmacological and disease data, thereby providing a tool to evaluate the pleiotropic effect of large compound libraries and existing drugs 6 . There are many examples of the successful identification of novel therapeutic strategies based on systems biology [7][8][9][10] . In this study, bioactive compounds with known protein targets have been screened in silico using a systems biology-based approach 11 for their potential to target CLL microenvironment.…”

Section: Systems Biology Drug Screening Identifies Statins As Enhancementioning

confidence: 99%

Systems biology drug screening identifies statins as enhancers of current therapies in chronic lymphocytic leukemia

Giménez

Tripathi

Giró

et al. 2020

Sci Rep

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Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. We used a platform for drug discovery based on systems biology and artificial intelligence, to identify drugs targeting key proteins described to have a role in the microenvironment. The selected compounds were screened in CLL cell lines in the presence of stromal cells to mimic the microenvironment and validated the best candidates in primary CLL cells. Our results showed that the commercial drug simvastatin was the most effective and selective out of the tested compounds. Simvastatin decreased CLL cell survival and proliferation as well as cell adhesion. Importantly, this drug enhanced the antitumor effect of venetoclax and ibrutinib. We proposed that systems biology approaches combined with pharmacological screening could help to find new drugs for CLL treatment and to predict new combinations with current therapies. Our results highlight the possibility of repurposing widely used drugs such as statins to target the microenvironment and to improve the efficacy of ibrutinib or venetoclax in CLL cells.

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“…hypertension, diabetes, etc), which also brings potentially adverse side effects, such as gastrointestinal problems, arrhythmias, weight gain, insomnia, dizziness, asthenia, etc. [ 15 , 16 ]. However, evidence suggests that an appropriate lifestyle can help manage and prevent MetS and its associated factors [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

High intensity interval training exercise-induced physiological changes and their potential influence on metabolic syndrome clinical biomarkers: a meta-analysis

Serrablo-Torrejon

López-Valenciano

Ayuso³

et al. 2020

BMC Endocr Disord

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Background Despite the current debate about the effects of high intensity interval training (HIIT), HIIT elicits big morpho-physiological benefit on Metabolic Syndrome (MetS) treatment. However, no review or meta-analysis has compared the effects of HIIT to non-exercising controls in MetS variables. The aim of this study was to determine through a systematic review, the effectiveness of HIIT on MetS clinical variables in adults. Methods Studies had to be randomised controlled trials, lasting at least 3 weeks, and compare the effects of HIIT on at least one of the MetS clinical variables [fasting blood glucose (BG), high-density lipoprotein (HDL-C) triglyceride (TG), systolic (SBP) or diastolic blood pressure (DBP) and waist circumference (WC)] compared to a control group. The methodological quality of the studies selected was evaluated using the PEDro scale. Results Ten articles fulfilled the selection criteria, with a mean quality score on the PEDro scale of 6.7. Compared with controls, HIIT groups showed significant and relevant reductions in BG (− 0.11 mmol/L), SBP (− 4.44 mmHg), DBP (− 3.60 mmHg), and WC (− 2.26 cm). Otherwise, a slight increase was observed in HDL-C (+ 0.02 mmol/L). HIIT did not produce any significant changes in TG (− 1.29 mmol/L). Conclusions HIIT improves certain clinical aspects in people with MetS (BG, SBP, DBP and WC) compared to people with MetS who do not perform physical exercise. Plausible physiological changes of HIIT interventions might be related with large skeletal muscle mass implication, improvements in the vasomotor control, better baroreflex control, reduction of the total peripheral resistance, increases in excess post-exercise oxygen consumption, and changes in appetite and satiety mechanisms.

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A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome

Cited by 60 publications

References 71 publications

Integrative analyses of biomarkers and pathways for adipose tissue after bariatric surgery

Integrative analyses of biomarkers and pathways for adipose tissue after bariatric surgery

Systems biology drug screening identifies statins as enhancers of current therapies in chronic lymphocytic leukemia

High intensity interval training exercise-induced physiological changes and their potential influence on metabolic syndrome clinical biomarkers: a meta-analysis

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