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Article ; Online: Metabolic Alteration Bridging the Prediabetic State and Colorectal Cancer.

Colloca, Antonino / Donisi, Isabella / Anastasio, Camilla / Balestrieri, Maria Luisa / D'Onofrio, Nunzia

2024 Volume 13, Issue 8

Abstract: Prediabetes and colorectal cancer (CRC) represent compelling health burdens responsible for high mortality and morbidity rates, sharing several modifiable risk factors. It has been hypothesized that metabolic abnormalities linking prediabetes and CRC are ...

Abstract	Prediabetes and colorectal cancer (CRC) represent compelling health burdens responsible for high mortality and morbidity rates, sharing several modifiable risk factors. It has been hypothesized that metabolic abnormalities linking prediabetes and CRC are hyperglycemia, hyperinsulinemia, and adipokines imbalance. The chronic stimulation related to these metabolic signatures can favor CRC onset and development, as well as negatively influence CRC prognosis. To date, the growing burden of prediabetes and CRC has generated a global interest in defining their epidemiological and molecular relationships. Therefore, a deeper knowledge of the metabolic impairment determinants is compelling to identify the pathological mechanisms promoting the onset of prediabetes and CRC. In this scenario, this review aims to provide a comprehensive overview on the metabolic alterations of prediabetes and CRC as well as an overview of recent preventive and therapeutic approaches for both diseases, focusing on the role of the metabolic state as a pivotal contributor to consider for the development of future preventive and therapeutic strategies.
MeSH term(s)	Humans ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Prediabetic State/metabolism ; Animals ; Risk Factors
Language	English
Publishing date	2024-04-09
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13080663
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Editorial: Influence of lifestyle factors in the management of diabetes mellitus.

Sardu, Celestino / Santulli, Gaetano / D' Onofrio, Nunzia

Frontiers in endocrinology

2023 Volume 14, Page(s) 1258766

MeSH term(s)	Humans ; Diabetes Mellitus/therapy ; Life Style
Language	English
Publishing date	2023-08-10
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1258766
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Article ; Online: Dietary Epigenetic Modulators: Unravelling the Still-Controversial Benefits of miRNAs in Nutrition and Disease.

Martino, Elisa / D'Onofrio, Nunzia / Balestrieri, Anna / Colloca, Antonino / Anastasio, Camilla / Sardu, Celestino / Marfella, Raffaele / Campanile, Giuseppe / Balestrieri, Maria Luisa

Nutrients

2024 Volume 16, Issue 1

Abstract: In the context of nutrient-driven epigenetic alterations, food-derived miRNAs can be absorbed into the circulatory system and organs of recipients, especially humans, and potentially contribute to modulating health and diseases. Evidence suggests that ... ...

Abstract	In the context of nutrient-driven epigenetic alterations, food-derived miRNAs can be absorbed into the circulatory system and organs of recipients, especially humans, and potentially contribute to modulating health and diseases. Evidence suggests that food uptake, by carrying exogenous miRNAs (xenomiRNAs), regulates the individual miRNA profile, modifying the redox homeostasis and inflammatory conditions underlying pathological processes, such as type 2 diabetes mellitus, insulin resistance, metabolic syndrome, and cancer. The capacity of diet to control miRNA levels and the comprehension of the unique characteristics of dietary miRNAs in terms of gene expression regulation show important perspectives as a strategy to control disease susceptibility via epigenetic modifications and refine the clinical outcomes. However, the absorption, stability, availability, and epigenetic roles of dietary miRNAs are intriguing and currently the subject of intense debate; additionally, there is restricted knowledge of their physiological and potential side effects. Within this framework, we provided up-to-date and comprehensive knowledge on dietary miRNAs' potential, discussing the latest advances and controversial issues related to the role of miRNAs in human health and disease as modulators of chronic syndromes.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/genetics ; Nutritional Status ; Diet ; Epigenesis, Genetic ; MicroRNAs/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu16010160
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Article: MicroRNA-nanoparticles against cancer: Opportunities and challenges for personalized medicine.

Martino, Elisa / D'Onofrio, Nunzia / Anastasio, Camilla / Abate, Marianna / Zappavigna, Silvia / Caraglia, Michele / Balestrieri, Maria Luisa

Molecular therapy. Nucleic acids

2023 Volume 32, Page(s) 371–384

Abstract: Micro-RNAs (miRNAs) control gene expression at the post-transcriptional level and are widely involved in carcinogenesis, playing a role as both oncogenes and tumor suppressors. MiRNAs act as potent therapeutic weapon in cancer, but their potential ... ...

Abstract	Micro-RNAs (miRNAs) control gene expression at the post-transcriptional level and are widely involved in carcinogenesis, playing a role as both oncogenes and tumor suppressors. MiRNAs act as potent therapeutic weapon in cancer, but their potential therapeutic use is limited by the off-target effect due to their nonspecific distribution in normal tissues. The encapsulation of miRNAs in nanostructured carriers allows targeted effects aimed to destroy cancer cells, without affecting healthy tissues. Due to their small size and the optimal surface/size ratio, nanoparticles (NPs) envelop, protect, and release miRNAs, representing a promising strategy in cancer treatment. In the present review, we discuss the latest advances in the field of miRNA-encapsulating NPs in cancer, focusing on colorectal cancer and its metastatic forms, one of the most common malignancies worldwide.
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2023.03.021
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Article: MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11.

Martino, Elisa / Balestrieri, Anna / Aragona, Francesca / Bifulco, Giovanna / Mele, Luigi / Campanile, Giuseppe / Balestrieri, Maria Luisa / D'Onofrio, Nunzia

Cancers

2023 Volume 15, Issue 17

Abstract: Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. ... ...

Abstract	Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. Nevertheless, the role of miR-148a-3p in CRC remains largely undetermined. Here, we aim at investigating the molecular mechanisms and regulatory targets of miR-148a-3p in the CRC cell death mechanism(s). To this end, miR-148a-3p expression was evaluated in SW480 and SW620 cells and normal colon epithelial CCD 841 CoN cells with quantitative real-time polymerase chain reaction (qRT-PCR). Data reported a reduction of miR-148a-3p expression in SW480 and SW620 cells compared to non-tumor cells (
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15174342
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Article: Whey Improves In Vitro Endothelial Mitochondrial Function and Metabolic Redox Status in Diabetic State.

Martino, Elisa / Luce, Amalia / Balestrieri, Anna / Mele, Luigi / Anastasio, Camilla / D'Onofrio, Nunzia / Balestrieri, Maria Luisa / Campanile, Giuseppe

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 6

Abstract: Endothelial dysfunction plays a critical role in the progression of type 2 diabetes mellitus (T2DM), leading to cardiovascular complications. Current preventive antioxidant strategies to reduce oxidative stress and improve mitochondrial function in T2DM ... ...

Abstract	Endothelial dysfunction plays a critical role in the progression of type 2 diabetes mellitus (T2DM), leading to cardiovascular complications. Current preventive antioxidant strategies to reduce oxidative stress and improve mitochondrial function in T2DM highlight dietary interventions as a promising approach, stimulating the deepening of knowledge of food sources rich in bioactive components. Whey (WH), a dairy by-product with a considerable content of bioactive compounds (betaines and acylcarnitines), modulates cancer cell metabolism by acting on mitochondrial energy metabolism. Here, we aimed at covering the lack of knowledge on the possible effect of WH on the mitochondrial function in T2DM. The results showed that WH improved human endothelial cell (TeloHAEC) function during the in vitro diabetic condition mimicked by treating cells with palmitic acid (PA) (0.1 mM) and high glucose (HG) (30 mM). Of note, WH protected endothelial cells from PA+HG-induced cytotoxicity (
Language	English
Publishing date	2023-06-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12061311
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Article ; Online: Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer.

Colloca, Antonino / Balestrieri, Anna / Anastasio, Camilla / Balestrieri, Maria Luisa / D'Onofrio, Nunzia

International journal of molecular sciences

2022 Volume 23, Issue 6

Abstract: Sirtuins (SIRTs) are a family of class III histone deacetylases (HDACs) consisting of seven members, widely expressed in mammals. SIRTs mainly participate in metabolic homeostasis, DNA damage repair, cell survival, and differentiation, as well as other ... ...

Abstract	Sirtuins (SIRTs) are a family of class III histone deacetylases (HDACs) consisting of seven members, widely expressed in mammals. SIRTs mainly participate in metabolic homeostasis, DNA damage repair, cell survival, and differentiation, as well as other cancer-related biological processes. Growing evidence shows that SIRTs have pivotal roles in chronic degenerative diseases, including colorectal cancer (CRC), the third most frequent malignant disease worldwide. Metabolic alterations are gaining attention in the context of CRC development and progression, with mitochondrion representing a crucial point of complex and intricate molecular mechanisms. Mitochondrial SIRTs, SIRT2, SIRT3, SIRT4 and SIRT5, control mitochondrial homeostasis and dynamics. Here, we provide a comprehensive review on the latest advances on the role of mitochondrial SIRTs in the initiation, promotion and progression of CRC. A deeper understanding of the pathways by which mitochondrial SIRTs control CRC metabolism may provide new molecular targets for future innovative strategies for CRC prevention and therapy.
MeSH term(s)	Animals ; Colorectal Neoplasms/metabolism ; Homeostasis ; Mammals/metabolism ; Mitochondria/metabolism ; Sirtuin 3/metabolism ; Sirtuins/metabolism
Chemical Substances	Sirtuin 3 (EC 3.5.1.-) ; Sirtuins (EC 3.5.1.-)
Language	English
Publishing date	2022-03-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23063212
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Article ; Online: MiR-15b-5p and PCSK9 inhibition reduces lipopolysaccharide-induced endothelial dysfunction by targeting SIRT4.

Martino, Elisa / D'Onofrio, Nunzia / Balestrieri, Anna / Mele, Luigi / Sardu, Celestino / Marfella, Raffaele / Campanile, Giuseppe / Balestrieri, Maria Luisa

Cellular & molecular biology letters

2023 Volume 28, Issue 1, Page(s) 66

Abstract: Background: Endothelial dysfunction and deregulated microRNAs (miRNAs) participate in the development of sepsis and are associated with septic organ failure and death. Here, we explored the role of miR-15b-5p on inflammatory pathways in ... ...

Abstract	Background: Endothelial dysfunction and deregulated microRNAs (miRNAs) participate in the development of sepsis and are associated with septic organ failure and death. Here, we explored the role of miR-15b-5p on inflammatory pathways in lipopolysaccharide (LPS)-treated human endothelial cells, HUVEC and TeloHAEC. Methods: The miR-15b-5p levels were evaluated in LPS-stimulated HUVEC and TeloHAEC cells by quantitative real-time PCR (qRT-PCR). Functional experiments using cell counting kit-8 (CCK-8), transfection with antagomir, and enzyme-linked immunosorbent assays (ELISA) were conducted, along with investigation of pyroptosis, apoptosis, autophagy, and mitochondrial reactive oxygen species (ROS) by cytofluorometric analysis and verified by fluorescence microscopy. Sirtuin 4 (SIRT4) levels were detected by ELISA and immunoblotting, while proprotein convertase subtilisin-kexin type 9 (PCSK9) expression was determined by flow cytometry (FACS) and immunofluorescence analyses. Dual-luciferase reporter evaluation was performed to confirm the miR-15b-5p-SIRT4 interaction. Results: The results showed a correlation among miR-15b-5p, PCSK9, and SIRT4 levels in septic HUVEC and TeloHAEC. Inhibition of miR-15b-5p upregulated SIRT4 content, alleviated sepsis-related inflammatory pathways, attenuated mitochondrial stress, and prevented apoptosis, pyroptosis, and autophagic mechanisms. Finally, a PCSK9 inhibitor (i-PCSK9) was used to analyze the involvement of PCSK9 in septic endothelial injury. i-PCSK9 treatment increased SIRT4 protein levels, opposed the septic inflammatory cascade leading to pyroptosis and autophagy, and strengthened the protective role of miR-15b-5p inhibition. Increased luciferase signal validated the miR-15b-5p-SIRT4 binding. Conclusions: Our in vitro findings suggested the miR-15b-5p-SIRT4 axis as a suitable target for LPS-induced inflammatory pathways occurring in sepsis, and provide additional knowledge on the beneficial effect of i-PCSK9 in preventing vascular damage by targeting SIRT4.
MeSH term(s)	Humans ; Antagomirs ; Endothelial Cells/pathology ; Lipopolysaccharides ; Mitochondrial Proteins ; Proprotein Convertase 9 ; Sirtuins/genetics ; MicroRNAs
Chemical Substances	Antagomirs ; Lipopolysaccharides ; Mitochondrial Proteins ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; SIRT4 protein, human (EC 3.5.1.-) ; Sirtuins (EC 3.5.1.-) ; MIRN15 microRNA, human ; MicroRNAs
Language	English
Publishing date	2023-08-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2108724-6
ISSN	1689-1392 ; 1689-1392
ISSN (online)	1689-1392
ISSN	1689-1392
DOI	10.1186/s11658-023-00482-5
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Article ; Online: Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage.

Salzano, Angela / Fioriniello, Salvatore / D'Onofrio, Nunzia / Balestrieri, Maria Luisa / Aiese Cigliano, Riccardo / Neglia, Gianluca / Della Ragione, Floriana / Campanile, Giuseppe

BMC genomics

2023 Volume 24, Issue 1, Page(s) 133

Abstract: Background: Green feed diet in ruminants exerts a beneficial effect on rumen metabolism and enhances the content of milk nutraceutical quality. At present, a comprehensive analysis focused on the identification of genes, and therefore, biological ... ...

Abstract	Background: Green feed diet in ruminants exerts a beneficial effect on rumen metabolism and enhances the content of milk nutraceutical quality. At present, a comprehensive analysis focused on the identification of genes, and therefore, biological processes modulated by the green feed in buffalo rumen has never been reported. We performed RNA-sequencing in the rumen of buffaloes fed a total mixed ration (TMR) + the inclusion of 30% of ryegrass green feed (treated) or TMR (control), and identified differentially expressed genes (DEGs) using EdgeR and NOISeq tools. Results: We found 155 DEGs using EdgeR (p-values < 0.05) and 61 DEGs using NOISeq (prob ≥0.8), 30 of which are shared. The rt-qPCR validation suggested a higher reliability of EdgeR results as compared with NOISeq data, in our biological context. Gene Ontology analysis of DEGs identified using EdgeR revealed that green feed modulates biological processes relevant for the rumen physiology and, then, health and well-being of buffaloes, such as lipid metabolism, response to the oxidative stress, immune response, and muscle structure and function. Accordingly, we found: (i) up-regulation of HSD17B13, LOC102410803 (or PSAT1) and HYKK, and down-regulation of CDO1, SELENBP1 and PEMT, encoding factors involved in energy, lipid and amino acid metabolism; (ii) enhanced expression of SIM2 and TRIM14, whose products are implicated in the immune response and defense against infections, and reduced expression of LOC112585166 (or SAAL1), ROR2, SMOC2, and S100A11, encoding pro-inflammatory factors; (iii) up-regulation of NUDT18, DNAJA4 and HSF4, whose products counteract stressful conditions, and down-regulation of LOC102396388 (or UGT1A9) and LOC102413340 (or MRP4/ABCC4), encoding detoxifying factors; (iv) increased expression of KCNK10, CACNG4, and ATP2B4, encoding proteins modulating Ca Conclusion: Although statistically unpowered, this study suggests that green feed modulates the expression of genes involved in biological processes relevant for rumen functionality and physiology, and thus, for welfare and quality production in Italian Mediterranean dairy buffaloes. These findings, that need to be further confirmed through the validation of additional DEGs, allow to speculate a role of green feed in the production of nutraceutical molecules, whose levels might be enhanced also in milk.
MeSH term(s)	Animals ; Female ; Buffaloes/genetics ; Transcriptome ; Animal Feed/analysis ; Reproducibility of Results ; Diet/veterinary ; Milk/metabolism ; Rumen/metabolism ; Lactation ; Fermentation
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-023-09215-6
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Article: Diet‐derived ergothioneine induces necroptosis in colorectal cancer cells by activating the SIRT3/MLKL pathway

D'Onofrio, Nunzia / Martino, Elisa / Balestrieri, Anna / Mele, Luigi / Cautela, Domenico / Castaldo, Domenico / Balestrieri, Maria Luisa

FEBS letters. 2022 May, v. 596, no. 10

2022

Abstract: Ergothioneine (Egt) is a dietary amino acid which acts as an antioxidant to protect against ageing‐related diseases. We investigated the anti‐cancer properties of Egt in colorectal cancer cells (CRC). Egt treatment exerted cytotoxicity in a dose‐ ... ...

Abstract	Ergothioneine (Egt) is a dietary amino acid which acts as an antioxidant to protect against ageing‐related diseases. We investigated the anti‐cancer properties of Egt in colorectal cancer cells (CRC). Egt treatment exerted cytotoxicity in a dose‐dependent manner, induced reactive oxygen species accumulation, loss of mitochondrial membrane potential and upregulation of the histone deacetylase SIRT3. Immunoblotting analysis indicated that the cell death occurred via necroptosis through activation of the RIP1/RIP3/MLKL pathway. An immunoprecipitation assay unveiled that the interaction between the terminal effector in necroptotic signalling MLKL and SIRT3 increased during the Egt treatment. SIRT3 gene silencing blocked the upregulation of MLKL and abolished the ability of Egt to induce necroptosis. The SIRT3–MLKL interaction may mediate the necroptotic effects of Egt in CRC, suggesting the potential of this dietary amino thione in the prevention of CRC.
Keywords	amino acids ; colorectal neoplasms ; cytotoxicity ; dose response ; genes ; histone deacetylase ; immunoblotting ; membrane potential ; mitochondrial membrane ; necroptosis ; precipitin tests ; reactive oxygen species
Language	English
Dates of publication	2022-05
Size	p. 1313-1329.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14310
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