Publications

2025

Pacella, Daniela, Maria Lembo, Valentina Trimarco, Alessia Izzo, Maria Virginia Manzi, Stanislovas S Jankauskas, Imma Forzano, et al. “Dual Modulation of Lipid and Glucose Metabolism by a Nutraceutical Combination in Patients at Cardiometabolic Risk: Results from a Multicenter Randomized Controlled Trial.”. Cardiovascular Diabetology 24, no. 1 (2025): 384. https://doi.org/10.1186/s12933-025-02920-4.

BACKGROUND: Recent evidence suggests that inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a key enzyme in cholesterol biosynthesis, has beneficial effects on lipid metabolism and blood pressure (BP), but detrimental consequences on glycemia. Nutraceuticals (NUTs) containing both Monacolin K (MK) and Morus alba have been shown to be more effective in lowering lipids compared to NUT formulations containing only MK. However, the effects of these NUTs on glucose homeostasis have not been fully determined.

METHODS: To evaluate the association between LDL-C-lowering therapy and glycemia in patients receiving NUT combinations with or without Morus alba, we analyzed data from a prospective, randomized, active-treatment controlled trial (NCT02898805), which enrolled 359 patients to compare the effects of a NUT combination containing MK alone (Formulation 1, F1; n = 170) versus one containing MK and Morus alba (Formulation 1, F2; n = 189).

RESULTS: Participants in the two treatment arms (F1 vs. F2) were comparable in terms of sex, age, metabolic parameters, and BP. After 3 months, both groups experienced significant reductions in LDL-C, fasting plasma glucose, HbA1c, and HOMA index. F2 treatment led to a significantly greater reduction in glycemic levels compared to F1 treatment (b = - 16, p < 0.001). Notably, a divergent trend emerged over time: an inverse relationship between LDL-C and glycemic levels was observed in the F1 group, while a significant direct association between LDL-C and glycemic levels was detected in the F2 group (b = 0.06, p = 0.002).

CONCLUSIONS: Taken together, our findings indicate that the treatment with a NUT combination containing Morus alba simultaneously reduces plasma levels of LDL-C and glucose.

Santulli, Gaetano. “The 2025 AHA/ACC Hypertension Guidelines: Implications for Cardiovascular and Renal Risk in Patients With Diabetes.”. Cardiovascular Diabetology. Endocrinology Reports 11, no. 1 (2025): 21. https://doi.org/10.1186/s40842-025-00239-3.

Hypertension remains a major contributor to cardiovascular and renal complications in patients with diabetes mellitus, increasing the risk of macrovascular and microvascular disease. The 2025 AHA/ACC hypertension guidelines maintain a diagnostic and treatment threshold of 130/80 mmHg, emphasizing earlier and more intensive blood pressure control to reduce cardiovascular events, stroke, heart failure, and progression of diabetic nephropathy. Evidence from clinical trials and meta-analyses supports the benefits of tighter blood pressure targets, while acknowledging potential risks such as hypotension, electrolyte disturbances, and acute kidney injury. Management strategies combine pharmacologic therapy with lifestyle interventions including dietary modification, physical activity, weight management, and smoking cessation. Individualized blood pressure targets are recommended for older or frail patients to balance safety and benefit. Home and ambulatory blood pressure monitoring are highlighted for detecting masked or nocturnal hypertension, enhancing risk stratification, and supporting treatment titration. The guidelines also emphasize integrated risk assessment and multidisciplinary management. The 2025 AHA/ACC hypertension guidelines provide an evidence-based, patient-centered framework to optimize cardiovascular and renal outcomes in patients with diabetes, promoting early intervention, individualized therapy, and comprehensive risk reduction.

Pande, Shivangi, Fahimeh Varzideh, Jessica Gambardella, Stanislovas S Jankauskas, Federica Andrea Cerasuolo, Letizia Spinelli, Urna Kansakar, et al. “Fabry Disease Cardiomyopathy: A State-of-the-Art Review.”. Progress in Cardiovascular Diseases, 2025. https://doi.org/10.1016/j.pcad.2025.08.003.

Fabry disease or Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (GLA), leading to systemic accumulation of globotriaosyl-ceramide (Gb3). Initially described in 1898 as a dermatological condition, Fabry disease is now recognized as a progressive multisystem disorder with significant cardiac involvement. Cardiomyopathy in Fabry disease arises from Gb3 accumulation in cardiac tissue, resulting in structural changes such as fibrosis and left ventricular hypertrophy (LVH), and functional impairments including diastolic dysfunction and heart failure. The deacylated derivative, lysoGb3, serves as a biomarker of cardiac involvement. Diagnosis relies on enzyme assays, genetic testing, and advanced cardiac imaging modalities like echocardiography and cardiac MRI. Management strategies are centered around enzyme replacement therapy, and prognosis varies due to phenotypic heterogeneity and severity of disease progression. Psychological and social burdens further complicate patient care. However, underdiagnosis remains a concerning issue, particularly in individuals with unexplained cardiomyopathies. Early recognition through increased clinical awareness and genetic screening is crucial for timely intervention. Ongoing research is essential to develop new therapies targeting the genetic and metabolic roots of the disease. This systematic review comprehensively examines current evidence regarding the mechanisms, diagnosis, treatment, and prognosis of cardiomyopathy associated with Fabry disease, providing insight that may enhance clinical practice and guide future research initiatives.

Gatto, Cristina, Maria Rosaria Rusciano, Daniela Sorriento, Paola Di Pietro, Angela Carmelita Abate, Valeria Visco, Nicola Montone, et al. “Mitochondrial Accumulation of GRK2 As a Protective Mechanism Against Hypoxia-Induced Endothelial Dysfunction.”. Cell Death Discovery 11, no. 1 (2025): 324. https://doi.org/10.1038/s41420-025-02628-0.

Hypoxia, a condition characterized by a temporary lack of oxygen, causes mitochondrial damage, which in turn leads to endothelial dysfunction. G-protein-coupled receptor kinase 2 (GRK2) plays a key role in vascular homeostasis and remodeling, influencing endothelial function through various pathways. GRK2 moves within the cellular compartments and is linked to mitochondrial function and biogenesis, promoting ATP production and protecting against oxidative stress and cell death. The present study examined how mitochondrial GRK2 accumulation affects vascular reactivity and endothelial function in transient hypoxic conditions. Using a cloning strategy, we employed a small peptide (10aa) TAT-conjugated based on the pleckstrin homology domain of GRK2 to redirect GRK2 from the plasma membrane to the mitochondria. Mitochondrial accumulation of GRK2 increases vasodilatory responses in isolated swine artery segments, indicating potential therapeutic applications for cardiovascular disorders. Furthermore, in endothelial cells, GRK2 accumulation within mitochondria protects membrane potential, mitochondrial mass and prevents oxidative damage and cell death caused by transient hypoxia. Our findings show that GRK2 accumulation in mitochondria represents a potential therapeutic target to prevent transient hypoxia-induced damage.

Trimarco, Valentina, Raffaele Izzo, Daniela Pacella, Maria Virginia Manzi, Stanislovas S Jankauskas, Paola Gallo, Francesco Rozza, et al. “Aspirin Reduces the Risk of Type 2 Diabetes Associated With COVID-19.”. Npj Metabolic Health and Disease. 3, no. 1 (2025): 27. https://doi.org/10.1038/s44324-025-00072-3.

This study aimed to determine whether daily low-dose aspirin reduces the risk of type 2 diabetes (T2D) associated with COVID-19. A longitudinal cohort of 200,000 adults followed from 2018 to 2022 was analyzed, comparing T2D incidence between aspirin users and non-users. Propensity score matching was used to balance the groups. The incidence of T2D was substantially lower in the aspirin group, with Cox regression showing a 52% risk reduction. Kaplan-Meier analysis confirmed a significant divergence in cumulative T2D risk after two years. This protective effect was observed both before and during the COVID-19 pandemic, with a stronger association during the pandemic period. These findings indicate that daily low-dose aspirin significantly reduces the risk of COVID-19-associated new-onset T2D, highlighting the role of inflammation in the pathogenesis of T2D triggered or unmasked by COVID-19.

Trimarco, Valentina, Raffaele Izzo, Daniela Pacella, Maria Manzi V, Fahimeh Varzideh, Maria Lembo, Paola Gallo, et al. “The COVID-19 Pandemic Increased the Incidence of Newly Diagnosed Cancers: Evidence from a Large Cohort Study in Southern Italy.”. BMC Medicine 23, no. 1 (2025): 399. https://doi.org/10.1186/s12916-025-04237-1.

BACKGROUND: Recent studies based on hospital and outpatient clinic databases have reported a decline in cancer diagnoses during the COVID-19 pandemic, an observation that has been mainly attributed to halted screenings.

METHODS: We investigated the impact of COVID-19 on cancer incidence in the Campania Region (Italy) among adults followed by their primary care physicians over a 6-year period (2017-2022). Using a single-cohort design, we employed interrupted time series (ITS) analysis to compare cancer incidence rates during the 3 years preceding the pandemic (2017-2019) with those during the three pandemic years (2020-2022).

RESULTS: We analyzed data from 212,656 individuals and found that the incidence of new cancer diagnoses rose from 14.3 to 23.1 per 1000 person-years when comparing the pre-pandemic to the COVID-19 period. ITS analysis revealed a stable trend in cancer diagnoses before the pandemic, followed by a marked increase of  8 new cases per month beginning in January 2020, with a peak observed in August 2021. Notably, diagnoses of brain and skin cancers increased by 300% in 2022 compared to 2017.

CONCLUSIONS: Taken together, these findings highlight a concerning increase in cancer diagnoses in the Campania Region during the COVID-19 pandemic, contrasting with earlier reports that pointed to a decline in cases, mostly attributed to interrupted screening services. Several indirect factors might contribute to this trend, including heightened psychosocial stress and shifts in lifestyle behaviors, as well as profound disruptions in access to and continuity of healthcare delivery.