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1.
M2 muscarinic receptors negatively modulate cell migration in human glioblastoma cells.
Guerriero, C, Fanfarillo, R, Mancini, P, Sterbini, V, Guarguaglini, G, Sforna, L, Michelucci, A, Catacuzzeno, L, Tata, AM
Neurochemistry international. 2024;:105673
Abstract
Glioblastoma (GB) is a very aggressive human brain tumor. The high growth potential and invasiveness make this tumor surgically and pharmacologically untreatable. Our previous work demonstrated that the activation of the M2 muscarinic acetylcholine receptors (M2 mAChRs) inhibited cell proliferation and survival in GB cell lines and in the cancer stem cells derived from human biopsies. The aim of the present study was to investigate the ability of M2 mAChR to modulate cell migration in two different GB cell lines: U87 and U251. By wound healing assay and single cell migration analysis performed by time-lapse microscopy, we demonstrated the ability of M2 mAChRs to negatively modulate cell migration in U251 but not in the U87 cell line. In order to explain the different effects observed in the two cell lines we have evaluated the possible involvement of the intermediate conductance calcium-activated potassium (IKCa) channel. IKCa channel is present in the GB cells, and it has been demonstrated to modulate cell migration. Using the perforated patch-clamp technique we have found that selective activation of M2 mAChR significantly reduced functional density of the IKCa current in U251 but not in U87 cells. To understand whether the M2 mAChR mediated reduction of ion channel density in the U251 cell line was relevant for the cell migration impairment, we tested the effects of TRAM-34, a selective inhibitor of the IKCa channel, in wound healing assay. We found that it was able to markedly reduce U251 cell migration and significantly decrease the number of invadopodia-like structure formations. These results suggest that only in U251 cells the reduced cell migration M2 mAChR-mediated might involve, at least in part, the IKCa channel.
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2.
Biological Activities of Molecules Derived from Olea europaea L. Tested In Vitro.
Marrone, G, Urciuoli, S, Candi, E, Bernini, R, Vanni, G, Masci, C, Guerriero, C, Mancini, M, De Lorenzo, A, Vignolini, P, et al
Life (Basel, Switzerland). 2023;(1)
Abstract
BACKGROUND Extra virgin olive oil is a typical food of the Mediterranean area, obtained by pressing Olea europaea L. fruits. Its polyphenols have been studied for their antioxidant function and protective action against cancer and chronic kidney disease. In this in vitro study, we tested titrated extracts from Olea europaea L. on a human embryonic kidney 293 (HEK-293E) cell line, regarding their pro-apoptotic and antiproliferative capacities, using " IncuCyte® S3 Live-Cell Analysis System". MATERIALS AND METHODS We selected Olea europaea L. active compounds like hydroxytyrosol (HT) and oleuropein (OLE). These extracts were tested at different concentrations and characterized by HPLC-DAD-MS for the content in secondary active metabolites. The real-time observation of cell behavior was performed by IncuCyte, which can quantitatively analyze the cell proliferation and death. RESULTS This study showed that all the tested extracts can significantly inhibit cellular growth at 50 µM but the reduced proliferation is not related to an increase in cellular apoptosis. Instead, the same analysis performed by using extracts at 100 µM reveals that they can inhibit cellular growth, further inducing cellular apoptosis. CONCLUSIONS The results on the HEK-293E cells confirmed the antiproliferative and proapoptotic actions of active compounds from an Olea europaea L. matrix in this cell line.
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3.
Linking Migraine to Gut Dysbiosis and Chronic Non-Communicable Diseases.
Di Lauro, M, Guerriero, C, Cornali, K, Albanese, M, Costacurta, M, Mercuri, NB, Di Daniele, N, Noce, A
Nutrients. 2023;(20)
Abstract
In the world, migraine is one of the most common causes of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers in combination with a genetic predisposition. Among the factors related to migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this context, in addition to conventional pharmacological treatments for migraine, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity, and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, such as diabetes mellitus, arterial hypertension, obesity, cancer, and chronic kidney diseases, whose link is represented by gut dysbiosis.
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4.
Extra Virgin Olive Oil and Cardiovascular Protection in Chronic Kidney Disease.
Marrone, G, Urciuoli, S, Di Lauro, M, Ruzzolini, J, Ieri, F, Vignolini, P, Di Daniele, F, Guerriero, C, Nediani, C, Di Daniele, N, et al
Nutrients. 2022;(20)
Abstract
The high mortality related to chronic kidney disease (CKD) is not only due to the disease itself; in fact, CKD also represents an important risk factor for cardiovascular (CV) morbidity and mortality. Among the functional foods that seems to have cardioprotective action, extra virgin olive oil (EVOO) plays a pivotal health-promoting role. The aim of this study was to evaluate the possible cardioprotective effects of an EVOO containing a very high content (>900 ppm) of minor phenolic compounds (MPCs). The selected EVOO was analyzed by HPLC-DAD-MS to establish the MPC content. The Olea extract obtained from the selected EVOO was tested against the RAW 264.7 cell line in order to investigate its anti-inflammatory activity. We enrolled 40 CKD patients under conservative therapy for in vivo clinical testing. All CKD patients consumed 40 mL/day of raw EVOO for 9 weeks (T1). At baseline (T0) and at T1, we monitored the patients’ blood and urinary parameters. The patients’ body composition was assessed using bioelectrical impedance analysis and the carotid intima-media thickness (CIMT) using ultrasound imaging. At T1, we observed a decrease in inflammatory parameters, CIMT, and oxidative stress biomarkers. We also noticed improvements in lipid and purine metabolism, atherogenic indices, and body composition. Thus, this study highlighted the cardioprotective action of EVOO in nephropathic patients.
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5.
Effects of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Stages: A Case-Control Study.
Albanese, M, Marrone, G, Paolino, A, Di Lauro, M, Di Daniele, F, Chiaramonte, C, D'Agostini, C, Romani, A, Cavaliere, A, Guerriero, C, et al
Pharmaceuticals (Basel, Switzerland). 2022;(2)
Abstract
Ultramicronized palmitoylethanolamide (um-PEA), a compound with antioxidant, anti-inflammatory and neuroprotective properties, appears to be a potential adjuvant treatment for early stages of Coronavirus disease 2019 (COVID-19). In our study, we enrolled 90 patients with confirmed diagnosis of COVID-19 that were randomized into two groups, homogeneous for age, gender and BMI. The first group received oral supplementation based on um-PEA at a dose of 1800 mg/day for a total of 28 days; the second group was the control group (R.S. 73.20). At baseline (T0) and after 28 days of um-PEA treatment (T1), we monitored: routine laboratory parameters, inflammatory and oxidative stress (OS) biomarkers, lymphocytes subpopulation and COVID-19 serological response. At T1, the um-PEA-treated group presented a significant reduction in inflammation compared to the control group (CRP p = 0.007; IL-6 p = 0.0001; neutrophils to lymphocytes ratio p = 0.044). At T1, the controls showed a significant increase in OS compared to the treated group (FORT p = 0.05). At T1, the um-PEA group exhibited a significant decrease in D-dimer levels (p = 0.0001) and higher levels of IgG against SARS-CoV-2 (p = 0.0001) compared to the controls. Our data demonstrated, in a randomized clinical trial, the beneficial effects of um-PEA in both asymptomatic and mild-symptomatic patients related to reductions in inflammatory state, OS and coagulative cascade alterations.
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6.
Vegan Diet Health Benefits in Metabolic Syndrome.
Marrone, G, Guerriero, C, Palazzetti, D, Lido, P, Marolla, A, Di Daniele, F, Noce, A
Nutrients. 2021;13(3)
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Plain language summary
Plant-based diets (PBD) have grown in popularity in recent years and have been associated with better health outcomes especially with heart disease, however poorly planned PBD’s can result in nutrient deficiencies like vitamin B12. This review aimed to summarise the health benefits of PBD’s, especially vegan diets, compared to omnivorous diets when looking at risk factors associated with heart disease. The authors started by summarising three PBD’s obvious in the literature; vegan diet with no animal products, lacto-ovo-vegetarian (LOV) with dairy products and eggs, and fish-vegetarian including fish and seafoods. The study then highlighted the strengths and weaknesses of the vegan diet, highlighting that although the vegan diet represents a healthy way of eating rich in carbohydrates, omega-6 fats, fibre, vitamin C, vitamin E and magnesium it can be low in protein, omega-3 fats, vitamin B12, vitamin D, calcium, iron, zinc and iodine if not properly planned. Heart disease incidence was reported to be lower in individuals on a PBD, especially vegans, when compared to omnivorous diets possibly due to their improvement on risk factors associated with the disease. Metabolic syndrome, blood pressure, fat production, and blood sugar balance were all shown to be improved and reasons such as their high fibre content reducing energy intake and causing feelings of satiety and their low saturated fat content impacting cholesterol production were listed as possible mechanisms behind the improvements. It was concluded that a nutritionist led, vegan diet can improve risk factors for heart disease resulting in better health outcomes. This study could be used by healthcare practitioners to understand where vegan diets may lack certain nutrients and the Importance of a well-planned vegan diet in the prevention of heart disease in those at an increased risk.
Abstract
Plant-based diets (PBDs) are increasingly consumed by the Italian population and around the world. In particular, among PBDs, the vegan diet is a food pattern characterized by the exclusion of all animal-origin foods. What drives people to adopt this model are mainly ethical, health and environmental reasons. A vegan diet, if well-balanced and varied, can help in achieving and maintaining an optimal state of health. However, this nutritional approach, if not well-balanced, can cause deficiencies in proteins, ω-3 fatty acids, iron, vitamin D and calcium, zinc, iodine and, above all, vitamin B12. Oral food supplements especially fortified foods are recommended in these cases to restore the nutritional deficiencies. A vegan diet generally reduces the risk of developing chronic non-communicable degenerative diseases, such as metabolic syndrome (MetS) and, in addition, requires fewer natural resources for food production than an omnivorous diet. The aim of this review is to analyze the possible impact of the vegan diet on MetS onset and its treatment.
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7.
Uremic Sarcopenia and Its Possible Nutritional Approach.
Noce, A, Marrone, G, Ottaviani, E, Guerriero, C, Di Daniele, F, Pietroboni Zaitseva, A, Di Daniele, N
Nutrients. 2021;(1)
Abstract
Uremic sarcopenia is a frequent condition present in chronic kidney disease (CKD) patients and is characterized by reduced muscle mass, muscle strength and physical performance. Uremic sarcopenia is related to an increased risk of hospitalization and all-causes mortality. This pathological condition is caused not only by advanced age but also by others factors typical of CKD patients such as metabolic acidosis, hemodialysis therapy, low-grade inflammatory status and inadequate protein-energy intake. Currently, treatments available to ameliorate uremic sarcopenia include nutritional therapy (oral nutritional supplement, inter/intradialytic parenteral nutrition, enteral nutrition, high protein and fiber diet and percutaneous endoscopic gastrectomy) and a personalized program of physical activity. The aim of this review is to analyze the possible benefits induced by nutritional therapy alone or in combination with a personalized program of physical activity, on onset and/or progression of uremic sarcopenia.
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8.
Impact of Physical Activity and Natural Bioactive Compounds on Endothelial Dysfunction in Chronic Kidney Disease.
Grazioli, E, Romani, A, Marrone, G, Di Lauro, M, Cerulli, C, Urciuoli, S, Murri, A, Guerriero, C, Tranchita, E, Tesauro, M, et al
Life (Basel, Switzerland). 2021;(8)
Abstract
Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.
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9.
Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients.
Noce, A, Albanese, M, Marrone, G, Di Lauro, M, Pietroboni Zaitseva, A, Palazzetti, D, Guerriero, C, Paolino, A, Pizzenti, G, Di Daniele, F, et al
Pharmaceuticals (Basel, Switzerland). 2021;(4)
Abstract
The Coronavirus Disease-19 (COVID-19) pandemic has caused more than 100,000,000 cases of coronavirus infection in the world in just a year, of which there were 2 million deaths. Its clinical picture is characterized by pulmonary involvement that culminates, in the most severe cases, in acute respiratory distress syndrome (ARDS). However, COVID-19 affects other organs and systems, including cardiovascular, urinary, gastrointestinal, and nervous systems. Currently, unique-drug therapy is not supported by international guidelines. In this context, it is important to resort to adjuvant therapies in combination with traditional pharmacological treatments. Among natural bioactive compounds, palmitoylethanolamide (PEA) seems to have potentially beneficial effects. In fact, the Food and Drug Administration (FDA) authorized an ongoing clinical trial with ultramicronized (um)-PEA as an add-on therapy in the treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. In support of this hypothesis, in vitro and in vivo studies have highlighted the immunomodulatory, anti-inflammatory, neuroprotective and pain-relieving effects of PEA, especially in its um form. The purpose of this review is to highlight the potential use of um-PEA as an adjuvant treatment in SARS-CoV-2 infection.
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10.
Efficacy and tolerability of topical 0.2% Myrtacine® and 4% vitamin PP for prevention and treatment of retinoid dermatitis in patients with mild to moderate acne.
Veraldi, S, Giovene, GL, Guerriero, C, Bettoli, V
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2012;(5):491-7
Abstract
AIM: The aim of the present study was to evaluate the efficacy and tolerability of an emulsion of 0.2% Myrtacine® and 4% vitamin PP, compared with a simple emollient cream, in the treatment of retinoid dermatitis in patients with mild-to-moderate acne. METHODS This was a prospective, multicenter, open-label, non-randomised, parallel-group study. Patients (age 12-49 years; skin phototype I-IV) with mild-to-moderate acne, who were treated with a topical retinoid for at least one month and had developed skin irritation were assigned to one of the two following treatments: 0.2% Myrtacine® and 4% vitamin PP (N.=116) or a simple emollient cream (N.=48). Both treatments were administered twice daily, 1-1.5 hours after the application of the topical retinoid. Study endpoints were improvement in signs and symptoms of retinoid dermatitis, global efficacy, reduction in acne severity, overall clinical outcome, patient satisfaction and tolerability. RESULTS At day 28, compared with the simple emollient cream, 0.2% Myrtacine® and 4% vitamin PP significantly decreased signs (erythema, dryness/scaling, oedema, and roughness) and symptoms (itching, stinging, burning sensation and discomfort) of retinoid dermatitis (P<0.01). In addition, compared with the simple emollient cream, 0.2% Myrtacine® and 4% vitamin PP decreased acne severity in a significantly greater proportion of patients (P=0.023) and was associated with a better clinical outcome (mild, intermediate, clinically relevant or global improvement; P<0.001). 0.2% Myrtacine® and 4% vitamin PP was also associated with greater patient satisfaction and was better tolerated than the simple emollient cream. CONCLUSION 0.2% Myrtacine® and 4% vitamin PP was effective and well tolerated in the treatment of retinoid dermatitis in patients with mild-to-moderate acne and significantly improved acne severity and overall clinical outcome.