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Article: Corrigendum: miR-21 in Human Cardiomyopathies.

Surina / Fontanella, Rosaria Anna / Scisciola, Lucia / Marfella, Raffaele / Paolisso, Giuseppe / Barbieri, Michelangela

2022 Volume 9, Page(s) 913429

Abstract: This corrects the article DOI: 10.3389/fcvm.2021.767064.]. ...

Abstract	[This corrects the article DOI: 10.3389/fcvm.2021.767064.].
Language	English
Publishing date	2022-04-25
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.913429
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Article ; Online: Circulating biomarkers of inflammaging and Alzheimer's disease to track age-related trajectories of dementia: Can we develop a clinically relevant composite combination?

Abbatecola, Angela Marie / Giuliani, Angelica / Biscetti, Leonardo / Scisciola, Lucia / Battista, Petronilla / Barbieri, Michelangela / Sabbatinelli, Jacopo / Olivieri, Fabiola

Ageing research reviews

2024 Volume 96, Page(s) 102257

Abstract: Alzheimer's disease (AD) is a rapidly growing global concern due to a consistent rise of the prevalence of dementia which is mainly caused by the aging population worldwide. An early diagnosis of AD remains important as interventions are plausibly more ... ...

Abstract	Alzheimer's disease (AD) is a rapidly growing global concern due to a consistent rise of the prevalence of dementia which is mainly caused by the aging population worldwide. An early diagnosis of AD remains important as interventions are plausibly more effective when started at the earliest stages. Recent developments in clinical research have focused on the use of blood-based biomarkers for improve diagnosis/prognosis of neurodegenerative diseases, particularly AD. Unlike invasive cerebrospinal fluid tests, circulating biomarkers are less invasive and will become increasingly cheaper and simple to use in larger number of patients with mild symptoms or at risk of dementia. In addition to AD-specific markers, there is growing interest in biomarkers of inflammaging/neuro-inflammaging, an age-related chronic low-grade inflammatory condition increasingly recognized as one of the main risk factor for almost all age-related diseases, including AD. Several inflammatory markers have been associated with cognitive performance and AD development and progression. The presence of senescent cells, a key driver of inflammaging, has also been linked to AD pathogenesis, and senolytic therapy is emerging as a potential treatment strategy. Here, we describe blood-based biomarkers clinically relevant for AD diagnosis/prognosis and biomarkers of inflammaging associated with AD. Through a systematic review approach, we propose that a combination of circulating neurodegeneration and inflammatory biomarkers may contribute to improving early diagnosis and prognosis, as well as providing valuable insights into the trajectory of cognitive decline and dementia in the aging population.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/pathology ; Cognitive Dysfunction/diagnosis ; Aging ; Biomarkers/cerebrospinal fluid ; Amyloid beta-Peptides
Chemical Substances	Biomarkers ; Amyloid beta-Peptides
Language	English
Publishing date	2024-03-02
Publishing country	England
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2024.102257
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Article ; Online: On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?

Scisciola, Lucia / Olivieri, Fabiola / Ambrosino, Concetta / Barbieri, Michelangela / Rizzo, Maria Rosaria / Paolisso, Giuseppe

Ageing research reviews

2023 Volume 92, Page(s) 102131

Abstract: Here we propose that SGLT2 inhibitors (SGLT2i), a class of drugs primarily used to treat type 2 diabetes, could also be repositioned as anti-aging senomorphic drugs (agents that prevent the extrinsic harmful effects of senescent cells). As observed for ... ...

Abstract	Here we propose that SGLT2 inhibitors (SGLT2i), a class of drugs primarily used to treat type 2 diabetes, could also be repositioned as anti-aging senomorphic drugs (agents that prevent the extrinsic harmful effects of senescent cells). As observed for metformin, another anti-diabetic drug with established anti-aging potential, increasing evidence suggests that SGLT2i can modulate some relevant pathways associated with the aging process, such as free radical production, cellular energy regulation through AMP-activated protein kinase (AMPK), autophagy, and the activation of nuclear factor (NF)-kB/inflammasome. Some interesting pro-healthy effects were also observed on human microbiota. All these mechanisms converge on fueling a systemic proinflammatory condition called inflammaging, now recognized as the main risk factor for accelerated aging and increased risk of age-related disease development and progression. Inflammaging can be worsened by cellular senescence and immunosenescence, which contributes to the increased burden of senescent cells during aging, perpetuating the proinflammatory condition. Interestingly, increasing evidence suggested the direct effects of SGLT-2i against senescent cells, chronic activation of immune cells, and metabolic alterations induced by overnutrition (meta-inflammation). In this framework, we analyzed and discussed the multifaceted impact of SGLT2i, compared with metformin effects, as a potential anti-aging drug beyond diabetes management. Despite promising results in experimental studies, rigorous investigations with well-designed cellular and clinical investigations will need to validate SGLT2 inhibitors' anti-aging effects.
MeSH term(s)	Humans ; Aging ; Cellular Senescence ; Diabetes Mellitus, Type 2/drug therapy ; Metformin/pharmacology ; Metformin/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
Chemical Substances	Metformin (9100L32L2N) ; Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2023-11-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2023.102131
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Article ; Online: Do immune checkpoint inhibitors share the same pharmacological feature in the risk of cardiac arrhythmias?

Mascolo, Annamaria / Sportiello, Liberata / Rafaniello, Concetta / Donniacuo, Maria / Ruggiero, Donatella / Scisciola, Lucia / Barbieri, Michelangela / Rossi, Francesco / Paolisso, Giuseppe / Capuano, Annalisa

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 164, Page(s) 114912

Abstract: Background: Despite the available evidence showing an association between cardiac arrhythmia and Immune Checkpoint Inhibitors (ICIs), few studies have compared this risk between ICIs.: Objectives: We aim to evaluate Individual Case Safety Reports ( ... ...

Abstract	Background: Despite the available evidence showing an association between cardiac arrhythmia and Immune Checkpoint Inhibitors (ICIs), few studies have compared this risk between ICIs. Objectives: We aim to evaluate Individual Case Safety Reports (ICSRs) of ICIs-induced cardiac arrhythmias and compare the reporting frequency of cardiac arrhythmias among ICIs. Methods: ICSRs were retrieved from the European Pharmacovigilance database (Eudravigilance). ICSRs were classified based on the ICI reported (pembrolizumab, nivolumab, atezolizumab, ipilimumab, durvalumab, avelumab, cemiplimab, and dostarlimab). If more than one ICI was reported, the ICSR was classified as a combination of ICIs. ICSRs of ICI-related arrhythmias were described and the reporting frequency of cardiac arrhythmias was assessed by applying the reporting odds ratio (ROR) and its 95 % confidence interval (95 %CI). Results: A total of 1262 ICSRs were retrieved, of which 147 (11.65 %) were related to combinations of ICIs. A total of 1426 events of cardiac arrhythmias were identified. The three most reported events were atrial fibrillation, tachycardia, and cardiac arrest. Ipilimumab was associated with a reduced reporting frequency of cardiac arrhythmias compared to all other ICIs (ROR 0.71, 95 %CI 0.55-0.92; p = 0.009). Anti-PD1 was associated with a higher reporting frequency of cardiac arrhythmias than anti-CTLA4 (ROR 1.47, 95 %CI 1.14-1.90; p = 0.003). Conclusion: This study is the first comparing ICIs for the risk of cardiac arrhythmias. We found that ipilimumab was the only ICI associated with a reduced reporting frequency. Further high-quality studies are needed to confirm our results.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors/adverse effects ; Antineoplastic Agents, Immunological ; Ipilimumab ; Pharmacovigilance ; Atrial Fibrillation
Chemical Substances	Immune Checkpoint Inhibitors ; Antineoplastic Agents, Immunological ; Ipilimumab
Language	English
Publishing date	2023-05-19
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.114912
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Article: Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line.

Scisciola, Lucia / Fontanella, Rosaria Anna / Surina / Garofalo, Giovanna / Rizzo, Maria Rosaria / Paolisso, Giuseppe / Barbieri, Michelangela

Frontiers in pharmacology

2022 Volume 13, Page(s) 868365

Abstract: The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and ... ...

Abstract	The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and platelets), and cardiac myocytes have the potential to damage vascular cells directly and cardiac myocytes, initiating mechanisms that induce apoptosis, inflammation, necrosis, and fibrosis of myocardial cells. In addition to reducing blood pressure, lisinopril, a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, increases the antioxidant defense in animals and humans. Recently, it has been shown that lisinopril can attenuate renal oxidative injury in the l-NAME-induced hypertensive rat and cause an impressive improvement in the antioxidant defense system of Wistar rats treated with doxorubicin. The potential effect of lisinopril on oxidative damage and fibrosis in human cardiomyocytes has not been previously investigated. Thus, the present study aims to investigate the effect of different doses of lisinopril on oxidative stress and fibrotic mediators in AC16 human cardiomyocytes, along with a 7-day presence in the culture medium. The results revealed that AC16 human cardiomyocytes exposed to lisinopril treatment significantly showed an upregulation of proteins involved in protecting against oxidative stress, such as catalase, SOD2, and thioredoxin, and a reduction of osteopontin and Galectin-3, critical proteins involved in cardiac fibrosis. Moreover, lisinopril treatment induced an increment in Sirtuin 1 and Sirtuin 6 protein expression. These findings demonstrated that, in AC16 human cardiomyocytes, lisinopril could protect against oxidative stress and fibrosis
Language	English
Publishing date	2022-05-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.868365
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Article ; Online: Tirzepatide prevents neurodegeneration through multiple molecular pathways.

Fontanella, Rosaria Anna / Ghosh, Puja / Pesapane, Ada / Taktaz, Fatemeh / Puocci, Armando / Franzese, Martina / Feliciano, Maria Federica / Tortorella, Giovanni / Scisciola, Lucia / Sommella, Eduardo / Ambrosino, Concetta / Paolisso, Giuseppe / Barbieri, Michelangela

Journal of translational medicine

2024 Volume 22, Issue 1, Page(s) 114

Abstract: Background: Several evidence demonstrated that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce the risk of dementia in type 2 diabetes patients by improving memory, learning, and overcoming cognitive impairment. In this study, we elucidated ... ...

Abstract	Background: Several evidence demonstrated that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce the risk of dementia in type 2 diabetes patients by improving memory, learning, and overcoming cognitive impairment. In this study, we elucidated the molecular processes underlying the protective effect of Tirzepatide (TIR), a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP-RA)/ GLP-1RA, against learning and memory disorders. Methods: We investigated the effects of TIR on markers of neuronal growth (CREB and BDNF), apoptosis (BAX/Bcl2 ratio) differentiation (pAkt, MAP2, GAP43, and AGBL4), and insulin resistance (GLUT1, GLUT4, GLUT3 and SORBS1) in a neuroblastoma cell line (SHSY5Y) exposed to normal and high glucose concentration. The potential role on DNA methylation of genes involved in neuroprotection and epigenetic modulators of neuronal growth (miRNA 34a), apoptosis (miRNA 212), and differentiation (miRNA 29c) was also investigated. The cell proliferation was detected by measuring Ki-67 through flow cytometry. The data were analysed by SPSS IBM Version 23 or GraphPad Prism 7.0 software and expressed as the means ± SEM. Differences between the mean values were considered significant at a p-value of < 0.05. GraphPad Prism software was used for drawing figures. Results: For the first time, it was highlighted: (a) the role of TIR in the activation of the pAkt/CREB/BDNF pathway and the downstream signaling cascade; (b) TIR efficacy in neuroprotection; (c) TIR counteracting of hyperglycemia and insulin resistance-related effects at the neuronal level. Conclusions: We demonstrated that TIR can ameliorate high glucose-induced neurodegeneration and overcome neuronal insulin resistance. Thus, this study provides new insight into the potential role of TIR in improving diabetes-related neuropathy.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Insulin/metabolism ; Insulin Resistance ; Brain-Derived Neurotrophic Factor ; Blood Glucose/metabolism ; MicroRNAs ; Glucagon-Like Peptide-1 Receptor/agonists ; Hypoglycemic Agents/pharmacology ; Glucagon-Like Peptide-2 Receptor ; Gastric Inhibitory Polypeptide
Chemical Substances	tirzepatide (OYN3CCI6QE) ; Insulin ; Brain-Derived Neurotrophic Factor ; Blood Glucose ; MicroRNAs ; Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents ; MIRN212 microRNA, human ; Glucagon-Like Peptide-2 Receptor ; Gastric Inhibitory Polypeptide (59392-49-3)
Language	English
Publishing date	2024-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-024-04927-z
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Article ; Online: Evidence that tirzepatide protects against diabetes-related cardiac damages.

Taktaz, Fatemeh / Scisciola, Lucia / Fontanella, Rosaria Anna / Pesapane, Ada / Ghosh, Puja / Franzese, Martina / Tortorella, Giovanni / Puocci, Armando / Sommella, Eduardo / Signoriello, Giuseppe / Olivieri, Fabiola / Barbieri, Michelangela / Paolisso, Giuseppe

Cardiovascular diabetology

2024 Volume 23, Issue 1, Page(s) 112

Abstract: Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their ... ...

Abstract	Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. Methods: A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. Results: Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r Conclusion: Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.
MeSH term(s)	Humans ; Heart Failure/prevention & control ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/drug therapy ; Hypertrophy ; Hypoglycemic Agents/pharmacology ; Myocytes, Cardiac ; Fibrosis ; Glucose ; Glucagon-Like Peptide-1 Receptor ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide-2 Receptor ; Gastric Inhibitory Polypeptide
Chemical Substances	tirzepatide (OYN3CCI6QE) ; Hypoglycemic Agents ; Glucose (IY9XDZ35W2) ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptide-2 Receptor ; Gastric Inhibitory Polypeptide (59392-49-3)
Language	English
Publishing date	2024-03-30
Publishing country	England
Document type	Meta-Analysis ; Journal Article
ZDB-ID	2093769-6
ISSN	1475-2840 ; 1475-2840
ISSN (online)	1475-2840
ISSN	1475-2840
DOI	10.1186/s12933-024-02203-4
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Article: Autonomic Nervous System and Cognitive Impairment in Older Patients: Evidence From Long-Term Heart Rate Variability in Real-Life Setting.

Dalise, Anna Maria / Prestano, Raffaele / Fasano, Renata / Gambardella, Antonio / Barbieri, Michelangela / Rizzo, Maria Rosaria

Frontiers in aging neuroscience

2020 Volume 12, Page(s) 40

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2020-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2020.00040
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Article: miR-21 in Human Cardiomyopathies.

Surina, Surina / Fontanella, Rosaria Anna / Scisciola, Lucia / Marfella, Raffaele / Paolisso, Giuseppe / Barbieri, Michelangela

Frontiers in cardiovascular medicine

2021 Volume 8, Page(s) 767064

Abstract: miR-21 is a 22-nucleotide long microRNA that matches target mRNAs in a complementary base pairing fashion and regulates gene expression by repressing or degrading target mRNAs. miR-21 is involved in various cardiomyopathies, including heart failure, ... ...

Abstract	miR-21 is a 22-nucleotide long microRNA that matches target mRNAs in a complementary base pairing fashion and regulates gene expression by repressing or degrading target mRNAs. miR-21 is involved in various cardiomyopathies, including heart failure, dilated cardiomyopathy, myocardial infarction, and diabetic cardiomyopathy. Expression levels of miR-21 notably change in both heart and circulation and provide cardiac protection after heart injury. In the meantime, miR-21 also tightly links to cardiac dysfunctions such as cardiac hypertrophy and fibrosis. This review focuses on the miR-21 expression pattern and its functions in diseased-heart and further discusses the feasibility of miR-21 as a biomarker and therapeutic target in cardiomyopathies.
Language	English
Publishing date	2021-10-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2021.767064
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Article: Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk.

Scisciola, Lucia / Fontanella, Rosaria Anna / Surina / Cataldo, Vittoria / Paolisso, Giuseppe / Barbieri, Michelangela

Life (Basel, Switzerland)

2021 Volume 11, Issue 2

Abstract: Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with ... ...

Abstract	Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or more cognitive domains as language, memory, reasoning, social cognition, planning, making decisions, and solving problems. Although the exact mechanism relating to sarcopenia and cognitive function has not yet been defined, several studies have shown that skeletal muscle produces and secrete molecules, called myokines, that regulate brain functions, including mood, learning, locomotor activity, and neuronal injury protection, showing the existence of muscle-brain cross-talk. Moreover, studies conducted on physical exercise supported the existence of muscle-brain cross-talk, showing how physical activity, changing myokines' circulating levels, exerts beneficial effects on the brain. The review mainly focuses on describing the role of myokines on brain function and their involvement in cognitive impairment in sarcopenia.
Language	English
Publishing date	2021-02-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life11020173
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