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Article ; Online: Adipocyte PI3K links adipostasis with baseline insulin secretion at fasting through an adipoincretin effect.

Becattini, Barbara / Molinaro, Angela / Henricsson, Marcus / Borén, Jan / Solinas, Giovanni

2024 Volume 43, Issue 5, Page(s) 114132

Abstract: Insulin-PI3K signaling controls insulin secretion. Understanding this feedback mechanism is crucial for comprehending how insulin functions. However, the role of adipocyte insulin-PI3K signaling in controlling insulin secretion in vivo remains unclear. ... ...

Abstract	Insulin-PI3K signaling controls insulin secretion. Understanding this feedback mechanism is crucial for comprehending how insulin functions. However, the role of adipocyte insulin-PI3K signaling in controlling insulin secretion in vivo remains unclear. Using adipocyte-specific PI3Kα knockout mice (PI3Kα
Language	English
Publishing date	2024-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.114132
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Article: PI3K and AKT at the Interface of Signaling and Metabolism.

Solinas, Giovanni / Becattini, Barbara

Current topics in microbiology and immunology

2022 Volume 436, Page(s) 311–336

Abstract: The PI3K/AKT signaling module is recruited by several receptors implicated in maintaining tissue and metabolic homeostasis and signaling pathways controlling immune responses. Constitutive activation of PI3K/AKT signaling leads to tissue overgrowth and ... ...

Abstract	The PI3K/AKT signaling module is recruited by several receptors implicated in maintaining tissue and metabolic homeostasis and signaling pathways controlling immune responses. Constitutive activation of PI3K/AKT signaling leads to tissue overgrowth and is frequently observed in cancer cells, whereas reduced PI3K/AKT signaling is associated with diabetes and growth defects. Thus, a critical roadblock to effective PI3K-targeted therapy comes from the crucial role of PI3K/AKT signaling in systemic metabolic homeostasis. This chapter describes the role of PI3K/AKT in insulin signaling and metabolic homeostasis and the interplay between insulin action and metabolic feedback loops that cause resistance to PI3K-targeted therapies. Furthermore, we provide examples of insulin-independent roles for PI3K/AKT in metabolic homeostasis, and some generalizations on the action of PI3K/AKT signaling at the interface of signaling and metabolism are derived. Finally, the specific roles for different class I PI3K isoforms in controlling systemic metabolic homeostasis and energy balance are discussed. We conclude that defining the functional specificities and redundancies of different class I PI3K isoforms in pathways driving disease and controlling metabolic homeostasis is fundamental to develop novel PI3K-targeted therapies.
MeSH term(s)	Insulin/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
Chemical Substances	Insulin ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2022-10-15
Publishing country	Germany
Document type	Journal Article
ISSN	0070-217X
ISSN	0070-217X
DOI	10.1007/978-3-031-06566-8_13
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Article: Heavy Metal(loid) Accumulation in the Ovarian Tissue of Free-Ranging Queens and Bitches Inhabiting Highly Polluted Urban Environments.

Forte, Giovanni / Ariu, Federica / Bocca, Beatrice / Solinas, Giuliana / Leoni, Giovanni Giuseppe / Podda, Andrea / Madeddu, Roberto / Bogliolo, Luisa

Animals : an open access journal from MDPI

2023 Volume 13, Issue 4

Abstract: There is strong scientific evidence that exposure to environmental contaminants, such as heavy metal(loid)s (HMs), can impair female reproductive function. Pets, such as cats and dogs, who share the same habitat as humans, may be particularly useful ... ...

Abstract	There is strong scientific evidence that exposure to environmental contaminants, such as heavy metal(loid)s (HMs), can impair female reproductive function. Pets, such as cats and dogs, who share the same habitat as humans, may be particularly useful sentinel models for detecting HMs in the ovary. In the present study, we compared the concentration of essential (Ems; Cu, Fe, Mn, Se, and Zn) and non-essential metal(loid)s (NEMs; Al, As, Cd, and Pb) in the ovarian tissues of free-ranging queens and bitches of different ages living in industrialized/highly polluted (south group) and non-polluted (north group) urban areas of the island of Sardinia, Italy. The results showed that both EMs and NEMs were present at detectable concentrations in feline and canine ovaries and their levels varied according to geographical areas and animal age. Among the EMs, Cu was found elevated in older queens and bitches inhabiting the southern area. Cadmium and lead were higher in feline and canine ovaries of older animals from the south compared to those living in the north. In addition, Cd and Pb concentrations increased in individuals of both species living in the south. These findings showed new perspectives for the use of pets as early warning sentinels of environmental pollution by HMs and for the risk of human exposure within a "One Health" approach. Pets may help to study the link between exposure to metals and female reproductive disturbances in mammals.
Language	English
Publishing date	2023-02-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani13040650
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Article ; Online: Clinical and hemodynamic outcomes of the Perceval sutureless aortic valve from a real-world registry.

Concistré, Giovanni / Baghai, Max / Santarpino, Giuseppe / Royse, Alistair / Scherner, Maximilian / Troise, Giovanni / Glauber, Mattia / Solinas, Marco

Interdisciplinary cardiovascular and thoracic surgery

2023 Volume 36, Issue 6

Abstract: Objectives: Perceval sutureless valve has been in clinical use for >15 years. The aim of this study is to report the real-word clinical and haemodynamic performance from the SURE-aortic valve replacement international prospective registry in patients ... ...

Abstract	Objectives: Perceval sutureless valve has been in clinical use for >15 years. The aim of this study is to report the real-word clinical and haemodynamic performance from the SURE-aortic valve replacement international prospective registry in patients who underwent aortic valve replacement with Perceval valve. Methods: From 2011 to 2021, patients from 55 institutions received a Perceval valve. Postoperative, follow-up, and echocardiographic outcomes were analysed. Results: A total of 1652 patients were included; mean age was 75.3 ± 7.0 years (53.9% female); mean EuroSCORE II was 4.1 ± 6.3. Minimally invasive approach was performed in 45.3% of patients; concomitant procedures were done in 35.9% of cases. Within 30 days, 0.3 and 0.7% valve-related reinterventions were reported. Transient ischaemic attack, disabling and non-disabling strokes were limited (0.4%, 0.4% and 0.7%, respectively). Pacemaker implant was required in 5.7% of patients. Intra-prosthetic regurgitation ≥2 was present in 0.2% of cases, while paravalvular leak ≥2 in only 0.1%. At a maximum follow-up of 8 years, 1.9% of cardiovascular deaths and 0.8% of valve-related reintervention occurred. Among the 10 cases of structural valve deterioration (mean 5.6 ± 1.4 years after implant; range: 2.6-7.3 years), 9 were treated with a transcatheter vale-in-valve implantation and 1 with explant. Mean pressure gradient decreased from 45.8 ± 16.5 mmHg preoperatively to 13.3 ± 5.2 mmHg at discharge and remained stable during follow-up. Conclusions: This experience represents the largest prospective real-world cohort of patients treated with Perceval showing that Perceval is a safe and effective alternative to conventional surgical aortic valve replacement, providing favourable clinical and haemodynamic results also at mid-term follow-up.
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article
ISSN	2753-670X
ISSN (online)	2753-670X
DOI	10.1093/icvts/ivad103
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Article ; Online: The role of PI3Kγ in metabolism and macrophage activation.

Solinas, Giovanni / Becattini, Barbara

Oncotarget

2017 Volume 8, Issue 63, Page(s) 106145–106146

Language	English
Publishing date	2017-10-25
Publishing country	United States
Document type	Editorial
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.22068
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Article ; Online: Heavy Metal(loid) Accumulation in the Ovarian Tissue of Free-Ranging Queens and Bitches Inhabiting Highly Polluted Urban Environments

Forte, Giovanni / Ariu, Federica / Bocca, Beatrice / Solinas, Giuliana / Leoni, Giovanni Giuseppe / Podda, Andrea / Madeddu, Roberto / Bogliolo, Luisa

Animals. 2023 Feb. 13, v. 13, no. 4

2023

Abstract	There is strong scientific evidence that exposure to environmental contaminants, such as heavy metal(loid)s (HMs), can impair female reproductive function. Pets, such as cats and dogs, who share the same habitat as humans, may be particularly useful sentinel models for detecting HMs in the ovary. In the present study, we compared the concentration of essential (Ems; Cu, Fe, Mn, Se, and Zn) and non-essential metal(loid)s (NEMs; Al, As, Cd, and Pb) in the ovarian tissues of free-ranging queens and bitches of different ages living in industrialized/highly polluted (south group) and non-polluted (north group) urban areas of the island of Sardinia, Italy. The results showed that both EMs and NEMs were present at detectable concentrations in feline and canine ovaries and their levels varied according to geographical areas and animal age. Among the EMs, Cu was found elevated in older queens and bitches inhabiting the southern area. Cadmium and lead were higher in feline and canine ovaries of older animals from the south compared to those living in the north. In addition, Cd and Pb concentrations increased in individuals of both species living in the south. These findings showed new perspectives for the use of pets as early warning sentinels of environmental pollution by HMs and for the risk of human exposure within a “One Health” approach. Pets may help to study the link between exposure to metals and female reproductive disturbances in mammals.
Keywords	animal age ; cadmium ; cats ; dogs ; females ; habitats ; heavy metals ; humans ; industrialization ; lead ; pollution ; risk ; Italy ; Sardinia
Language	English
Dates of publication	2023-0213
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani13040650
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Insulin signaling and glucose metabolism in different hepatoma cell lines deviate from hepatocyte physiology toward a convergent aberrant phenotype.

Molinaro, Angela / Becattini, Barbara / Solinas, Giovanni

Scientific reports

2020 Volume 10, Issue 1, Page(s) 12031

Abstract: Hepatoma cell lines are widely used to model the hepatocyte for insulin signaling and fatty liver disease. However, a direct comparison of insulin action in primary hepatocytes and in hepatoma cell lines is needed to validate this model and to better ... ...

Abstract	Hepatoma cell lines are widely used to model the hepatocyte for insulin signaling and fatty liver disease. However, a direct comparison of insulin action in primary hepatocytes and in hepatoma cell lines is needed to validate this model and to better understand liver cancer. Here we have investigated insulin signaling, gluconeogenic gene expression, glucose production, and fatty acid synthase abundance in primary hepatocytes and in HepG2, Hepa 1-6, and McARH7777 hepatoma cell lines. Differences in the electrophoretic profiles of protein extracts from human and mouse primary hepatocytes and the hepatoma cells lines are shown. Compared to primary hepatocytes, hepatoma cells showed high basal phosphorylation of AKT at Thr 308 and constitutively activated RAS-MAPK signaling, which were resistant to the dominant negative Ras mutant H-Ras17N. Hepatoma cell lines also showed defective expression of gluconeogenic enzymes, insulin unresponsive GSK phosphorylation, and marginal glucose production. Hepatoma cells also showed lower protein levels of fatty acid synthase and a largely distinct protein electrophoresis profile from hepatocytes but similar between different hepatoma lines. We conclude that hepatoma cell lines do not accurately model the hepatocyte for insulin action but may be valuable tools to investigate the proteomic changes conferring to hepatocellular carcinoma its peculiar metabolisms.
MeSH term(s)	Animals ; Carcinoma, Hepatocellular/metabolism ; Cell Line, Tumor ; Glucose/metabolism ; Hepatocytes/metabolism ; Humans ; Insulin/metabolism ; Liver Neoplasms/metabolism ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Phenotype ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; ras Proteins/metabolism
Chemical Substances	Insulin ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; ras Proteins (EC 3.6.5.2) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-07-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-68721-9
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Article ; Online: The oligometastatic setting in HNSCC: A critical review by the Rete Oncologica Piemonte e Valle d'Aosta multidisciplinary team.

Denaro, Nerina / Succo, Giovanni / Ostellino, Oliviero / Airoldi, Mario / Merlano, Marco Carlo / Badellino, Serena / Solinas, Cinzia / Garrone, Ornella / Iorio, Giuseppe Carlo

Critical reviews in oncology/hematology

2023 Volume 185, Page(s) 103968

Abstract: Introduction: The oligometastatic disease is a low burden metastatic disease that might still benefit from curable treatment. Squamous cell carcinoma of the head and neck (HNSCC) is a complex group of malignancies, with high rates of loco-regional ... ...

Abstract	Introduction: The oligometastatic disease is a low burden metastatic disease that might still benefit from curable treatment. Squamous cell carcinoma of the head and neck (HNSCC) is a complex group of malignancies, with high rates of loco-regional recurrences. Distant metastases are less frequent, and a single or few deposits are often observed (oligometastatic disease). The optimal management of oligometastatic HNSCC remains to be defined. Materials and methods: Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. Results: This paper contains a narrative report and a critical discussion of the available evidence on the management of oligometastatic HNSCC patients, with a focus on metastasis-directed therapy (MDT), particularly stereotactic ablative radiotherapy (SABR). Conclusions: in line with literature data, the multidisciplinary evaluation emerged as the key element in the management of oligometastatic HNSCC patients.
MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck/therapy ; Carcinoma, Squamous Cell/pathology ; Radiosurgery ; Head and Neck Neoplasms/therapy ; Patient Care Team
Language	English
Publishing date	2023-03-23
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2023.103968
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Article: Outcomes of Emergent Isolated Coronary Bypass Grafting in Heart Failure Patients.

Bianchi, Giacomo / Zancanaro, Edoardo / Margaryan, Rafik / Concistré, Giovanni / Varone, Egidio / Simeoni, Simone / Solinas, Marco

Life (Basel, Switzerland)

2022 Volume 12, Issue 12

Abstract: Patients with previously diagnosed HF are at greater risk for subsequent morbidity and mortality when hospitalized for an Acute Myocardial Infarction (AMI). The purpose of our study was to describe the time trend of the incidence of emergent CABG in ... ...

Abstract	Patients with previously diagnosed HF are at greater risk for subsequent morbidity and mortality when hospitalized for an Acute Myocardial Infarction (AMI). The purpose of our study was to describe the time trend of the incidence of emergent CABG in patients with and without HF, the clinical characteristics, outcomes, and the risk factors for mortality of surgical revascularization in the short and medium term. This was a single-center retrospective observational study of patients who underwent isolated emergency CABG from January 2009 to January 2020. A propensity-score matching analysis yielded two comparable groups (n = 430) of patients without (n = 215) and with (n = 215) heart failure. In-hospital mortality did not differ in the two groups (2.8%; p > 0.9); the patients with heart failure presented more frequently with cardiogenic shock, and there was an association with mortality and mechanical circulatory support (OR 16.7−95% CI 3.31−140; p = 0.002) and postoperative acute renal failure (OR 15.9−95% CI 0.66−203; p = 0.036). In the early- and mid-term, heart failure and NSTEMI were associated with mortality (HR 3.47−95% CI 1.15−10.5; p = 0.028), along with age (HR 1.28−95% CI 1.21−1.36; p < 0.001). Surgical revascularization offers an excellent solution for patients with acute coronary syndrome, leading to a good immediate prognosis even in those with chronic heart failure.
Language	English
Publishing date	2022-12-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12122124
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Article ; Online: Tubular

Dahlke, Eileen / Engmann, Toni / Anan, Yaman / Häsler, Robert / Solinas, Giovanni / Theilig, Franziska

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: Acute kidney injury (AKI) is a common renal injury leading to relevant morbidity and mortality worldwide. Most of the clinical cases of AKI are caused by ischemia reperfusion (I/R) injury with renal ischemia injury followed by reperfusion injury and ... ...

Abstract	Acute kidney injury (AKI) is a common renal injury leading to relevant morbidity and mortality worldwide. Most of the clinical cases of AKI are caused by ischemia reperfusion (I/R) injury with renal ischemia injury followed by reperfusion injury and activation of the innate immune response converging to NF-ĸB pathway induction. Despite the clear role of NF-ĸB in inflammation, it has recently been acknowledged that NF-ĸB may impact other cell functions. To identify NF-ĸB function with respect to metabolism, vascular function and oxidative stress after I/R injury and to decipher in detail the underlying mechanism, we generated a transgenic mouse model with targeted deletion of IKKβ along the tubule and applied I/R injury followed by its analysis after 2 and 14 days after I/R injury. Tubular IKKβ deletion ameliorated renal function and reduced tissue damage. RNAseq data together with immunohistochemical, biochemical and morphometric analysis demonstrated an ameliorated vascular organization and mRNA expression profile for increased angiogenesis in mice with tubular IKKβ deletion at 2 days after I/R injury. RNAseq and protein analysis indicate an ameliorated metabolism, oxidative species handling and timely-adapted cell proliferation and apoptosis as well as reduced fibrosis in mice with tubular IKKβ deletion at 14 days after I/R injury. In conclusion, mice with tubular IKKβ deletion upon I/R injury display improved renal function and reduced tissue damage and fibrosis in association with improved vascularization, metabolism, reactive species disposal and fine-tuned cell proliferation.
MeSH term(s)	Acute Kidney Injury/genetics ; Acute Kidney Injury/metabolism ; Animals ; Apoptosis/genetics ; Fibrosis ; I-kappa B Kinase/genetics ; Ischemia ; Kidney/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; NF-kappa B/metabolism ; Reperfusion Injury/genetics
Chemical Substances	NF-kappa B ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2022-09-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231710199
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