Dietary Intervention Modulates the Expression of Splicing Machinery in Cardiovascular Patients at High Risk of Type 2 Diabetes Development: From the CORDIOPREV Study

Río-Moreno, Mercedes del; Luque, Raúl M.; Rangel‐Zúñiga, Oriol A.; Alors‐Perez, Emilia; Alcalá‐Díaz, Juan F.; Roncero-Ramos, Irene; Camargo, Antonio; Gahete, Manuel D.; Castaño, Justo P.

doi:10.3390/nu12113528

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Our results are nicely in line with recent evidence from our group and others that dysregulation of the splicing machinery is a widespread feature among multiple diseases, from diverse cancers [10][11][12][13][14][15]20], to metabolic disorders [21,22], and chronic in ammatory diseases [23]. This study adds PMP to this growing line of evidence while, at the same time, provides precise information on the distinct, tumorspeci c alterations that occur in these rare tumors, which may become useful for the understanding and future management of the disease.…”

Section: Discussionsupporting

confidence: 92%

A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival

Moreno-Montilla

Alors‐Perez

Martínez-López³

et al. 2022

Preprint

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Purpose: Pseudomyxoma peritonei (PMP) is a rare cancer that causes chronic and uncontrollable mucus accumulation, gradually leading to intraperitoneal organ adhesion, bowel obstruction, malnutrition, and eventually cachexia and death. Aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy offer the best results; but the probability of relapse remains high. The study of the distinct molecular layers underlying PMP is essential to understand its genesis and progression. Alternative splicing is emerging as a new player in all cancers, but its role in PMP is unknown. The aim of this work was to assess the splicing machinery status in PMP and determine its potential contribution to disease prognosis. Methods: A set of 62 splicing-related genes were evaluated in a cohort of 29 patients using a microfluidic array, and their levels were compared between tumor and non-tumor tissue and correlated to relevant clinical parameters. Selected components were validated by immunohistochemistry and subsequently studied in detail by enrichment analyses. Results: Results revealed a profound dysregulation of the splicing machinery at RNA/protein level, which allowed to distinguish between tumor and control tissues. Particularly, the splicing factors HNRNPK, MBNL1, PTBP1 and RAVER1were associated with poor prognosis and their expression was linked to TP53regulation and inflammation processes. Conclusions: These findings provide the first evidence for the dysregulation of the splicing machinery in PMP, suggesting that it could be functionally altered and play a role in this rare malignant disease. Therefore, its detailed understanding could help to identify novel prognostic biomarkers and therapeutic targets in PMP.

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Section: Discussionsupporting

confidence: 92%

A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival

Moreno-Montilla

Alors‐Perez

Martínez-López³

et al. 2022

Preprint

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“…Total RNA from PBMCs was isolated using Direct-zol RNA kit (Zymo Research, Irvine, CA, USA) following manufacturer's instructions and as previously described (43,50,51). The amount of RNA recovered was determined and its quality assessed by the NanoDrop2000 spectrophotometer (Thermo Fisher).…”

Section: Rna Extraction Quantification and Reverse Transcriptionmentioning

confidence: 99%

Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment

Herrera-Martínez,

Castillo-Peinado,

Molina-Puerta

et al. 2023

Front. Endocrinol.

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BackgroundObesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation.AimThis study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities.Patients and methodsEpidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed.ResultsSignificant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia.ConclusionThe beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS.

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“…Total RNA from PBMCs was isolated using Direct-zol RNA kit (Zymo Research, Irvine, CA, USA) following the manufacturer's instructions, as previously described [13,19,20]. The amount of RNA recovered was determined and its quality assessed by the Nan-oDrop2000 spectrophotometer (Thermo Fisher, Madrid, Spain).…”

Section: Rna Extraction Quantification and Reverse Transcriptionmentioning

confidence: 99%

Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition

Leon-Idougourram

Pérez‐Gómez

Jiménez

et al. 2022

Cancers

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Malnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.

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Dietary Intervention Modulates the Expression of Splicing Machinery in Cardiovascular Patients at High Risk of Type 2 Diabetes Development: From the CORDIOPREV Study

Cited by 9 publications

References 40 publications

A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival

A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival

Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment

Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition

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