Publications by authors named "Olga Scudiero"

50 Publications

Multidisciplinary In-Depth Investigation in a Young Athlete Suffering from Syncope Caused by Myocardial Bridge.

Diagnostics (Basel) 2021 Nov 19;11(11). Epub 2021 Nov 19.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.

Laboratory medicine, along with genetic investigations in sports medicine, is taking on an increasingly important role in monitoring athletes' health conditions. Acute or intense exercise can result in metabolic imbalances, muscle injuries or reveal cardiovascular disorders. This study aimed to monitor the health status of a basketball player with an integrated approach, including biochemical and genetic investigations and advanced imaging techniques, to shed light on the causes of recurrent syncope he experienced during exercise. Biochemical analyses showed that the athlete had abnormal iron, ferritin and bilirubin levels. Coronary Computed Tomographic Angiography highlighted the presence of an intramyocardial bridge, suggesting this may be the cause of the observed syncopes. The athlete was excluded from competitive activity. In order to understand if this cardiac malformation could be caused by an inherited genetic condition, both array-CGH and whole exome sequencing were performed. Array-CGH showed two intronic deletions involving and genes, which could be related to a congenital heart defect; whole exome sequencing highlighted the genotype compatible with Gilbert syndrome. However, no clear pathogenic mutations related to the patient's cardiological phenotype were detected, even after applying machine learning methods. This case report highlights the importance and the need to provide exhaustive personalized diagnostic work up for the athletes in order to cover the cause of their malaise and for safeguarding their health. This multidisciplinary approach can be useful to create ad personam training and treatments, thus avoiding the appearance of diseases and injuries which, if underestimated, can become irreversible disorders and sometimes can result in the death of the athlete.
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http://dx.doi.org/10.3390/diagnostics11112144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618222PMC
November 2021

Antimicrobial Peptides and Physical Activity: A Great Hope against COVID 19.

Microorganisms 2021 Jun 30;9(7). Epub 2021 Jun 30.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Antimicrobial peptides (AMPs), α- and β-defensins, possess antiviral properties. These AMPs achieve viral inhibition through different mechanisms of action. For example, they can: (i) bind directly to virions; (ii) bind to and modulate host cell-surface receptors, disrupting intracellular signaling; (iii) function as chemokines to augment and alter adaptive immune responses. Given their antiviral properties and the fact that the development of an effective coronavirus disease 2019 (COVID-19) treatment is an urgent public health priority, they and their derivatives are being explored as potential therapies against COVID-19. These explorations using various strategies, range from their direct interaction with the virus to using them as vaccine adjuvants. However, AMPs do not work in isolation, specifically in their role as potent immune modulators, where they interact with toll-like receptors (TLRs) and chemokine receptors. Both of these receptors have been shown to play roles in COVID-19 pathogenesis. In addition, it is known that a healthy lifestyle accompanied by controlled physical activity can represent a natural weapon against COVID-19. In competitive athletes, an increase in serum defensins has been shown to function as self-protection from the attack of microorganisms, consequently a controlled physical activity could act as a support to any therapies in fighting COVID-19. Therefore, including information on all these players' interactions would produce a complete picture of AMP-based therapies' response.
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http://dx.doi.org/10.3390/microorganisms9071415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304224PMC
June 2021

Molecular Epidemiology of Mitochondrial Cardiomyopathy: A Search Among Mitochondrial and Nuclear Genes.

Int J Mol Sci 2021 May 27;22(11). Epub 2021 May 27.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.

Mitochondrial Cardiomyopathy (MCM) is a common manifestation of multi-organ Mitochondrial Diseases (MDs), occasionally present in non-syndromic cases. Diagnosis of MCM is complex because of wide clinical and genetic heterogeneity and requires medical, laboratory, and neuroimaging investigations. Currently, the molecular screening for MCM is fundamental part of MDs management and allows achieving the definitive diagnosis. In this article, we review the current genetic knowledge associated with MDs, focusing on diagnosis of MCM and MDs showing cardiac involvement. We searched for publications on mitochondrial and nuclear genes involved in MCM, mainly focusing on genetic screening based on targeted gene panels for the molecular diagnosis of the MCM, by using Next Generation Sequencing. Here we report twelve case reports, four case-control studies, eleven retrospective studies, and two prospective studies, for a total of twenty-nine papers concerning the evaluation of cardiac manifestations in mitochondrial diseases. From the analysis of published causal mutations, we identified 130 genes to be associated with mitochondrial heart diseases. A large proportion of these genes (34.3%) encode for key proteins involved in the oxidative phosphorylation system (OXPHOS), either as directly OXPHOS subunits (22.8%), and as OXPHOS assembly factors (11.5%). Mutations in several mitochondrial tRNA genes have been also reported in multi-organ or isolated MCM (15.3%). This review highlights the main disease-genes, identified by extensive genetic analysis, which could be included as target genes in next generation panels for the molecular diagnosis of patients with clinical suspect of mitochondrial cardiomyopathies.
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http://dx.doi.org/10.3390/ijms22115742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197938PMC
May 2021

Combined Effect of Mediterranean Diet and Aerobic Exercise on Weight Loss and Clinical Status in Obese Symptomatic Patients with Hypertrophic Cardiomyopathy.

Heart Fail Clin 2021 Apr 10;17(2):303-313. Epub 2021 Feb 10.

Cardiomyopathy Unit and Genetic Unit, Careggi University Hospital, Largo Brambrilla, 50134 Florence, Italy.

We evaluated the impact of weight loss (WL) using a Mediterranean diet and mild-to-moderate-intensity aerobic exercise program, on clinical status of obese, symptomatic patients with hypertrophic cardiomyopathy (HCM). Compared with nonresponders, responders showed a significant reduction of left atrial diameter, left atrial volume index (LAVI), E/E'average, pulmonary artery systolic pressure (PASP), and a significant increase in Vo (%) and peak workload. Body mass index changes correlated with reduction in left atrial diameter, LAVI, E/E'average, PASP, and increase of Vo (mL/Kg/min), Vo (%), peak workload. Mediterranean diet and aerobic exercise is associated with clinical-hemodynamic improvement in obese symptomatic HCM patients.
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http://dx.doi.org/10.1016/j.hfc.2021.01.003DOI Listing
April 2021

Effects of the COVID-19 Pandemic on Job Activity, Dietary Behaviours and Physical Activity Habits of University Population of Naples, Federico II-Italy.

Int J Environ Res Public Health 2021 02 5;18(4). Epub 2021 Feb 5.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80121 Naples, Italy.

Coronaviruses (CoVs) are a large family of respiratory viruses that can cause mild to moderate illness. The new variant COVID-19 has started to spread rapidly since December 2019, posing a new threat to global health. To counter the spread of the virus, the Italian government forced the population to close all activities starting from 9 March 2020 to 4 May 2020. In this scenario, we conducted a cross-sectional study on a heterogeneous sample (average age of 28 ± 12 years, 62.6% females) of the University of Naples Federico II (Italy). The aim of the study was to describe the lifestyle change in the university population during quarantine for the COVID 19 pandemic. Participants compiled an online survey consisting of 3 sections: socio-demographic data, dietary behaviours, physical activity habits and psychological aspects. The different results by gender are: 90.8% of females continued to work from home (81.9% were students); 34.8% increased their physical activity; and, only 0.8% prefer ready meals. Whereas, the same percentage of men continued to work from home (90%), but only 72.1% were students ( < 0.001 vs. females), only 23.9% increased physical activity ( < 0.001) and 1.7% favous ready meals. Our data shows that the male population was more affected by isolation and quarantine reporting more unfavourable behavioural changes.
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http://dx.doi.org/10.3390/ijerph18041502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915794PMC
February 2021

Exercise, Immune System, Nutrition, Respiratory and Cardiovascular Diseases during COVID-19: A Complex Combination.

Int J Environ Res Public Health 2021 01 21;18(3). Epub 2021 Jan 21.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.

Coronaviruses (CoVs) represent a large family of RNA viruses that can infect different living species, posing a global threat to human health. CoVs can evade the immune response, replicate within the host, and cause a rapid immune compromise culminating in severe acute respiratory syndrome. In humans, the immune system functions are influenced by physical activity, nutrition, and the absence of respiratory or cardiovascular diseases. This review provides an in-depth study between the interactions of the immune system and coronaviruses in the host to defend against CoVs disease.
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http://dx.doi.org/10.3390/ijerph18030904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908487PMC
January 2021

Dietary Thiols: A Potential Supporting Strategy against Oxidative Stress in Heart Failure and Muscular Damage during Sports Activity.

Int J Environ Res Public Health 2020 12 16;17(24). Epub 2020 Dec 16.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Moderate exercise combined with proper nutrition are considered protective factors against cardiovascular disease and musculoskeletal disorders. However, physical activity is known not only to have positive effects. In fact, the achievement of a good performance requires a very high oxygen consumption, which leads to the formation of oxygen free radicals, responsible for premature cell aging and diseases such as heart failure and muscle injury. In this scenario, a primary role is played by antioxidants, in particular by natural antioxidants that can be taken through the diet. Natural antioxidants are molecules capable of counteracting oxygen free radicals without causing cellular cytotoxicity. In recent years, therefore, research has conducted numerous studies on the identification of natural micronutrients, in order to prevent or mitigate oxidative stress induced by physical activity by helping to support conventional drug therapies against heart failure and muscle damage. The aim of this review is to have an overview of how controlled physical activity and a diet rich in antioxidants can represent a "natural cure" to prevent imbalances caused by free oxygen radicals in diseases such as heart failure and muscle damage. In particular, we will focus on sulfur-containing compounds that have the ability to protect the body from oxidative stress. We will mainly focus on six natural antioxidants: glutathione, taurine, lipoic acid, sulforaphane, garlic and methylsulfonylmethane.
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http://dx.doi.org/10.3390/ijerph17249424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765667PMC
December 2020

The Hidden Fragility in the Heart of the Athletes: A Review of Genetic Biomarkers.

Int J Mol Sci 2020 Sep 12;21(18). Epub 2020 Sep 12.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.

Sudden cardiac death (SCD) is a devastating event which can also affect people in apparent good health, such as young athletes. It is known that intense and continuous exercise along with a genetic background that predisposes a person to the risk of fatal arrhythmias is a trigger for SCD. Therefore, knowledge of the athlete's genetic conditions underlying the onset of SCD must be extended, in order to develop new effective prevention and/or therapeutic strategies. Arrhythmic features occur across a broad spectrum of cardiac diseases, sometimes presenting with overlapping phenotypes. The genetic basis of arrhythmogenic disorders has been greatly highlighted in the last 30 years, and has shown marked heterogeneity. The advent of next-generation sequencing has constantly updated our understanding of the genetic basis of arrhythmogenic diseases and is laying the foundation for precision medicine. With the exception of a few clinical cases involving a single athlete showing a highly suspected phenotype for the presence of a heart disease, there are few studies to date that analysed the applicability of genetic testing on cohorts of athletes. This evidence shows that genetic testing can contribute to the diagnosis of up to 13% of athletes; however, the presence of clinical markers is essential. This review aims to provide a reference collection on current knowledge of the genetic basis of sudden cardiac death in athletes and to review updated evidence on the effectiveness of genetic testing in early identification of athletes at risk for SCD.
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http://dx.doi.org/10.3390/ijms21186682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555257PMC
September 2020

Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies.

Int J Mol Sci 2020 Sep 4;21(18). Epub 2020 Sep 4.

Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", 80131 Naples, Italy.

Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.
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http://dx.doi.org/10.3390/ijms21186462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554875PMC
September 2020

Urinary Biomarkers: Diagnostic Tools for Monitoring Athletes' Health Status.

Int J Environ Res Public Health 2020 08 20;17(17). Epub 2020 Aug 20.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Acute or intense exercise is sometimes related to infections of the urinary tract. It can also lead to incorrect hydration as well as incorrect glomerular filtration due to the presence of high-molecular-weight proteins that cause damage to the kidneys. In this context, our study lays the foundations for the use of a urine test in a team of twelve male basketball players as a means of monitoring numerous biochemical parameters, including pH, specific weight, color, appearance, presence of bacterial cells, presence of squamous cells, leukocytes, erythrocytes, proteins, glucose, ketones, bilirubin, hemoglobin, nitrite, and leukocyte esterase, to prevent and/or treat the onset of pathologies, prescribe personalized treatments for each athlete, and monitor the athletes' health status.
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http://dx.doi.org/10.3390/ijerph17176065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503896PMC
August 2020

Athlete's Passport: Prevention of Infections, Inflammations, Injuries and Cardiovascular Diseases.

J Clin Med 2020 Aug 6;9(8). Epub 2020 Aug 6.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Laboratory medicine in sports medicine is taking on an ever-greater role in the assessment and monitoring of an athlete's health condition. The acute or intense exercise practiced by elite athletes can lead to the appearance of infections, inflammations, muscle injuries or cardiovascular disorders, whose diagnosis is not always rapid and efficient, as there is no continuous monitoring of the athlete. The absence of such monitoring can have serious consequences in terms of recovery of the professional athlete. These imbalances can induce metabolic adaptations which translate into alterations of specific parameters in terms of concentration and activity. The aim of this study was to follow the variation of specific biochemical biomarkers in a basketball team participating to the maximum championship during different phases of the agonistic season. The evaluation of serum biomarkers can help doctors to safeguard the athlete's health and sports trainers to adapt workouts, thus avoiding the appearance of diseases and injuries that in some cases can be underestimated by becoming irreversible ailments that do not allow the athlete to return to a healthy state. This information can be useful to create athlete biologic passports.
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http://dx.doi.org/10.3390/jcm9082540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465786PMC
August 2020

Methicillin-Resistant : Risk for General Infection and Endocarditis Among Athletes.

Antibiotics (Basel) 2020 Jun 18;9(6). Epub 2020 Jun 18.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S.Pansini 5, 80131 Naples, Italy.

The first studies on (SA) infections in athletes were conducted in the 1980s, and examined athletes that perform in close physical contact, with particular attention to damaged or infected skin. Recent studies have used molecular epidemiology to shed light on the transmission of SA in professional athletes. These studies have shown that contact between athletes is prolonged and constant, and that these factors influence the appearance of infections caused by SA. These results support the need to use sanitary measures designed to prevent the appearance of SA infections. The factors triggering the establishment of SA within professional sports groups are the nasal colonization of SA, contact between athletes and sweating. Hence, there is a need to use the most modern molecular typing methods to evaluate the appearance of cutaneous SA disease. This review aims to summarize both the current SA infections known in athletes and the diagnostic methods employed for recognition, pointing to possible preventive strategies and the factors that can act as a springboard for the appearance of SA and subsequent transmission between athletes.
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http://dx.doi.org/10.3390/antibiotics9060332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345113PMC
June 2020

HNP-1 and HBD-1 as Biomarkers for the Immune Systems of Elite Basketball Athletes.

Antibiotics (Basel) 2020 Jun 7;9(6). Epub 2020 Jun 7.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Acute or strenuous exercise is sometimes related to upper respiratory tract infections in athletes. Practicing intense and regular exercise can lead to incorrect activation of the immune system, causing athletes to be excluded from training programs and competitions. Defensins are small antimicrobial peptides that are part of the innate immune system and dynamically involved in several biological activities. In this study, we highlight the role of human defensins in competitive basketball athletes. In particular, we consider the behavior of alpha- and beta-defensins together with white blood cells in a cohort of players. Moreover, we focus our attention on cortisol, a physiological indicator of stress, and testosterone, both of which are human hormones involved in muscle metabolism. The free-testosterone/cortisol ratio is considered to be an indicator of overtraining among athletes. This paper provides an up-to-date information of the role of human defensins as self-defense molecules during a continuous stressor such as long-term exercise, and it recognizes them as potential markers of infection.
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http://dx.doi.org/10.3390/antibiotics9060306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345027PMC
June 2020

Human Defensins: A Novel Approach in the Fight against Skin Colonizing a.

Antibiotics (Basel) 2020 04 21;9(4). Epub 2020 Apr 21.

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

is a microorganism capable of causing numerous diseases of the human skin. The incidence of skin infections reflects the conflict between the host skin's immune defenses and the virulence elements. Antimicrobial peptides (AMPs) are small protein molecules involved in numerous biological activities, playing a very important role in the innate immunity. They constitute the defense of the host's skin, which prevents harmful microorganisms from entering the epithelial barrier, including However, uses ambiguous mechanisms against host defenses by promoting colonization and skin infections. Our review aims to provide a reference collection on host-pathogen interactions in skin disorders, including infections and its resistance to methicillin (MRSA). In addition to these, we discuss the involvement of defensins and other innate immunity mediators (i.e., toll receptors, interleukin-1, and interleukin-17), involved in the defense of the host against the skin disorders caused by , and then focus on the evasion mechanisms developed by the pathogenic microorganism under analysis. This review provides the "state of the art" on molecular mechanisms underlying skin infection and the pharmacological potential of AMPs as a new therapeutic strategy, in order to define alternative directions in the fight against cutaneous disease.
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http://dx.doi.org/10.3390/antibiotics9040198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235756PMC
April 2020

Idiopathic Hypereosinophilia and Venous Thromboembolism: Is There a Pathophysiological or Clinical Link? Description of an Intriguing Clinical Case.

J Blood Med 2020 28;11:73-76. Epub 2020 Feb 28.

Thrombosis and Hemorrhagic Center, Humanitas Research Hospital and Humanitas University, Rozzano, Italy.

Thrombosis events usually occur after prolonged bedrest, pregnancy, hormonal therapy, recent surgery and in the presence of inherited or acquired thrombophilia. However, several other diseases are often associated with thrombosis although their frequency is not easily estimated. Eosinophilia is one of these conditions. From a clinical viewpoint it is very difficult to understand which conditions might lead to a thrombotic event because the underlying pathophysiological mechanisms are different. Here, we report a case of idiopathic hypereosinophilia associated to venous thromboembolism without any other associated prothrombotic condition.
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http://dx.doi.org/10.2147/JBM.S229074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055521PMC
February 2020

Physical Activity and Thrombophilic Risk in a Short Series.

J Blood Med 2020 30;11:39-42. Epub 2020 Jan 30.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Napoli, Italia.

The role of influence on protein C anticoagulant system and PC deficiency-related thrombophilic risk due to strenuous physical exercise is still under discussion. To investigate the modification of the protein C anticoagulant pathway after vigorous exercise, we measured ProC Global assay, a protein C activity dependent clotting time, in 20 healthy subjects before and immediately after maximal treadmill exercise, and at 5, 15, 30 and 60 min in the recovery phase. The most evident change was a shortening of ProC Global clotting time from the average basal value of 123 sec to 84 sec at 30 min in post-exercise. Our study shows that the coagulation unbalance observed after strenuous exercise and with no consequence in healthy individuals with normal PC level, could increase the thrombophilic risk in silent carriers of significant defects of the protein C system and occasionally trigger an episode of deep vein thrombosis.
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http://dx.doi.org/10.2147/JBM.S220566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996552PMC
January 2020

Beyond cholesterol metabolism: The pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Genetics, mutations, expression, and perspective for long-term inhibition.

Biofactors 2020 May 30;46(3):367-380. Epub 2020 Jan 30.

Division of Clinical Cardiology, A.O.R.N. "Sant'Anna e San Sebastiano", Caserta, Italy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, particularly due to its function in low-density lipoprotein receptor degradation. Gain-of-function genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol-lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL-C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue-specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long-term pharmacological inhibition.
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http://dx.doi.org/10.1002/biof.1619DOI Listing
May 2020

Childhood obesity: an overview of laboratory medicine, exercise and microbiome.

Clin Chem Lab Med 2020 08 10;58(9):1385-1406. Epub 2019 Dec 10.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.

In the last few years, a significant increase of childhood obesity incidence unequally distributed within countries and population groups has been observed, thus representing an important public health problem associated with several health and social consequences. Obese children have more than a 50% probability of becoming obese adults, and to develop pathologies typical of obese adults, that include type 2-diabetes, dyslipidemia and hypertension. Also environmental factors, such as reduced physical activity and increased sedentary activities, may also result in increased caloric intake and/or decreased caloric expenditure. In the present review, we aimed to identify and describe a specific panel of parameters in order to evaluate and characterize the childhood obesity status useful in setting up a preventive diagnostic approach directed at improving health-related behaviors and identifying predisposing risk factors. An early identification of risk factors for childhood obesity could definitely help in setting up adequate and specific clinical treatments.
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http://dx.doi.org/10.1515/cclm-2019-0789DOI Listing
August 2020

Beta-defensins and analogs in Helicobacter pylori infections: mRNA expression levels, DNA methylation, and antibacterial activity.

PLoS One 2019 19;14(9):e0222295. Epub 2019 Sep 19.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Napoli, Italy.

Antimicrobial peptides can protect the gastric mucosa from bacteria, but Helicobacter pylori (H. pylori) can equally colonize the gastric apparatus. To understand beta-defensin function in H. pylori-associated chronic gastritis, we investigated susceptibility, human beta-defensin mRNA expression, and DNA methylation changes to promoters in the gastric mucosa with or without H. pylori infection. We studied the expression of HBD2 (gene name DEFB4A), HBD3 (DEFB103A), and HBD4 (DEFB104) using real-time PCR in 15 control and 10 H. pylori infection patient gastric specimens. This study demonstrates that H. pylori infection is related to gastric enhancement of inducible HBD2, but inducible HBD3 and HBD4 expression levels remained unchanged. HBD2 gene methylation levels were overall higher in H. pylori-negative samples than in H. pylori-positive samples. We also assessed antimicrobial susceptibility using growth on blood agar. The H. pylori strain Tox+ was susceptible to all defensins tested and their analogs (3N, 3NI). These results show that HBD2 is involved in gastritis development driven by H. pylori, which facilitates the creation of an epigenetic field during H. pylori-associated gastric tumorigenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222295PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752957PMC
March 2020

A Novel View of Human Infections: Interplay between Microbiota and Beta-Defensins.

Biomolecules 2019 06 18;9(6). Epub 2019 Jun 18.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", 80131 Napoli, Italy.

The gut microbiota is significantly involved in the preservation of the immune system of the host, protecting it against the pathogenic bacteria of the stomach. The correlation between gut microbiota and the host response supports human gastric homeostasis. Gut microbes may be shifted in ()-infected individuals to advance gastric inflammation and distinguished diseases. Particularly interesting is the establishment of cooperation between gut microbiota and antimicrobial peptides (AMPs) of the host in the gastrointestinal tract. AMPs have great importance in the innate immune reactions to and participate in conservative co-evolution with an intricate microbiome. β-Defensins, a class of short, cationic, arginine-rich proteins belonging to the AMP group, are produced by epithelial and immunological cells. Their expression is enhanced during infection. In this review, we discuss the impact of the gut microbiome on the host response, with particular regard to β-defensins in -associated infections. In microbial infections, mostly in precancerous lesions induced by infection, these modifications could lead to different outcomes.
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http://dx.doi.org/10.3390/biom9060237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627275PMC
June 2019

Laboratory medicine: health evaluation in elite athletes.

Clin Chem Lab Med 2019 Sep;57(10):1450-1473

Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.

The need to evaluate the health status of an athlete represents a crucial aim in preventive and protective sports science in order to identify the best diagnostic strategy to improve performance and reduce risks related to physical exercise. In the present review we aim to define the main biochemical and haematological markers that vary significantly during and after sports training to identify risk factors, at competitive and professional levels and to highlight the set up of a specific parameter's panel for elite athletes. Moreover, we also intend to consider additional biomarkers, still under investigation, which could further contribute to laboratory sports medicine and provide reliable data that can be used by athlete's competent staff in order to establish personal attitudes and prevent sports injuries.
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http://dx.doi.org/10.1515/cclm-2018-1107DOI Listing
September 2019

Adiponectin and Orexin-A as a Potential Immunity Link Between Adipose Tissue and Central Nervous System.

Front Physiol 2018 24;9:982. Epub 2018 Jul 24.

Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Adipose tissue (AT) is strongly associated with development and progression of immune disorders through adipokines secretion, such as adiponectin. This protein has beneficial energetic properties and is involved in inflammation and immunity processes. Three oligomers of circulating adiponectin with different molecular weight are described: High (HMW), Medium (MMW), and Low (LMW). The HMW is the most biologically active oligomers. On binding to its receptors AdipoR1, AdipoR2, and T-cadherin, adiponectin acts on both innate and acquired immunity. The suppression of NF-κB activation and pro-inflammatory cytokine expression in macrophages is mediated by AdipoR1. AdipoR2 mediates polarization of anti-inflammatory M2 macrophages T-cadherin is essential for the M2 macrophage proliferation. Furthermore, adiponectin reduces T cells responsiveness and B cells lymphopoiesis. The immune system is very sensitive to environmental changes and it is not only interconnected with AT but also with the central nervous system (CNS). Cytokines, which are mediators of the immune system, exercise control over mediators of the CNS. Microglia, which are immunity cells belonging to the macrophage family, are present within the CNS. The nervous system is also involved in immunity through the production of neuropeptides such as orexin-A/hypocretin-1. This neuropeptide is involved in metabolic disorders, inflammation and in the immune response. The relationship between adipokines, immunity, and the nervous system is validated by both the role of orexin-A on fat, food intake, and energy expenditure, as well as by role of adiponectin on the CNS. In this review, we focused on the functions of adiponectin and orexin-A as a potential immunity link between AT and CNS.
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http://dx.doi.org/10.3389/fphys.2018.00982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094989PMC
July 2018

Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625.

Sci Rep 2017 08 25;7(1):9434. Epub 2017 Aug 25.

Department of Pharmacy and CiRPEB- University of Naples "Federico II", Via Mezzocannone 16, 80134, Napoli, Italy.

gH625 constitutes a promising delivery vehicle for the transport of therapeutic biomacromolecules across membrane barriers. We report an application of multivalency to create a complex nanosystem for delivery and to elucidate the mechanism of peptide-lipid bilayer interactions. Multivalency may offer a route to enhance gH625 cellular uptake as demonstrated by results obtained on dimers of gH625 by fluorescence spectroscopy, circular dichroism, and surface plasmon resonance. Moreover, using both phase contrast and light sheet fluorescence microscopy we were able to characterize and visualize for the first time the fusion of giant unilamellar vesicles caused by a membranotropic peptide.
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http://dx.doi.org/10.1038/s41598-017-09001-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572722PMC
August 2017

Total and High Molecular Weight Adiponectin Expression Is Decreased in Patients with Common Variable Immunodeficiency: Correlation with Ig Replacement Therapy.

Front Immunol 2017 31;8:895. Epub 2017 Jul 31.

Department of Translational Medical Sciences, Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy.

Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic properties. It circulates as low molecular weight (LMW), medium molecular weight (MMW), and high molecular weight (HMW) oligomers. The latter exerts the most potent biological effects. Acrp30 attracted renewed interest with the finding that it was associated with the development and progression of immune disorders. The mechanisms underlying this association and the role of Acrp30 in the pathophysiology of immune-mediated conditions remain unknown. Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by chronic activation of the immune system, impaired antibody production, and imbalanced cytokine production. In the attempt to shed light on the expression of Acrp30 in CVID, we: (a) investigated total Acrp30 and its oligomerization state in CVID patients undergoing maintenance Ig replacement therapy; (b) assessed the effects of Ig replacement therapy on Acrp30 expression in treatment-naïve CVID patients, namely, patients not treated before diagnosis, before and after the first Ig administration; and (c) evaluated the correlation between Acrp30 levels and clinical phenotypes of the disease. As controls, we analyzed healthy subjects and patients affected by a non-immunodeficiency chronic inflammatory demyelinating polyneuropathy (CIDP), before and after Ig infusion. We found that total Acrp30 and HMW oligomers were decreased in CVID but not in CIDP patients versus controls. Moreover, Acrp30 levels were correlated with IgA levels and were associated with two CVID phenotypes, namely, autoimmune cytopenia and enteropathy. Receiver operating characteristic curve analysis indicated that Acrp30 modulation is specific for CVID patients. Acrp30 and HMW levels quickly and dramatically increased after Ig infusion only in eight treatment-naïve CVID patients but not in five CIDP patients. This finding indicates that Ig administration is not able to induce an increase of Acrp30, but the specific cellular and/or molecular background proper of CVID seems to be essential. In conclusion, our data indicate that Acrp30 is specifically related to CVID activity. Further studies are required to understand the biological role of Acrp30 and its possible use as disease biomarker in CVID.
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http://dx.doi.org/10.3389/fimmu.2017.00895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534466PMC
July 2017

Cyclic Peptides as Novel Therapeutic Microbicides: Engineering of Human Defensin Mimetics.

Molecules 2017 07 20;22(7). Epub 2017 Jul 20.

CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy.

Cyclic peptides are receiving significant attention thanks to their antimicrobial activity and high serum stability, which is useful to develop and design novel antimicrobial agents. Antimicrobial peptides appear to be key components of innate defences against bacteria, viruses, and fungi. Among the others, defensins possess a strong microbicidial activity. Defensins are cationic and amphipathic peptides with six cysteine residues connected by three disulfide bonds found in plants, insects, and mammals; they are divided in three families: α-, β-, and θ-defensins. α-Defensins are contained in the primary granules of human neutrophils; β-defensins are expressed in human epithelia; and θ-defensins are pseudo-cyclic defensins not found in humans, but in rhesus macaques. The structural diversities among the three families are reflected in a different antimicrobial action as well as in serum stability. The engineering of these peptides is an exciting opportunity to obtain more functional antimicrobial molecules highlighting their potential as therapeutic agents. The present review reports the most recent advances in the field of cyclic peptides with a specific regard to defensin analogs.
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http://dx.doi.org/10.3390/molecules22071217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152268PMC
July 2017

Adiponectin down-regulates CREB and inhibits proliferation of A549 lung cancer cells.

Pulm Pharmacol Ther 2017 08 12;45:114-120. Epub 2017 May 12.

Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", Medical School, Via L. De Crecchio 7, 80138 Naples, Italy.

Introduction: Adipokines are known to play a relevant role in a number of cancer related molecular pathways. Adiponectin is a major adipokine with anti-inflammatory and beneficial metabolic actions. Furthermore, it has been shown to exert anti-carcinogenic effects in various tumor models and some clinical studies suggested an inverse relationship between circulating levels of adiponectin and an increased risk for development of malignancies. On the other hand, the cyclic AMP response element binding (CREB) transcription factor has been clearly linked to lung cancer.

Methods: we analyzed cell proliferation, cell cycle of A549 cells treated with adiponectin as well as CREB activation status in human lung adenocarcinoma A549 cells and in non-small cell lung cancer (NSCLC) samples.

Results: adiponectin treatment, at concentrations ranging between 5 and 50 μg/ml mimicking human serum levels, has a significant effect on reducing tumor cell proliferation of A549 cells, mainly by altering cell cycle progression. Importantly, we provide evidence that adiponectin clearly inhibits in a dose- and time-dependent manner CREB phosphorylation (activation) and, at least in part, also the level of CREB protein itself, preceding and accompanying the anti-proliferative effects in response to adiponectin. Moreover, in agreement with previous studies demonstrating that CREB over-expression occurs in many tumors, we also show by western-blotting from lung specimen that CREB is significantly up-regulated in NSCLC samples compared to adjacent normal tissues from six patients.

Conclusions: Overall, our results represent the first evidence of CREB inhibition by adiponectin and may provide new insight into therapeutic strategies for lung cancer.
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http://dx.doi.org/10.1016/j.pupt.2017.05.009DOI Listing
August 2017

Adiponectin profile and Irisin expression in Italian obese children: Association with insulin-resistance.

Cytokine 2017 06 3;94:8-13. Epub 2017 Apr 3.

CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy; Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Seconda Università degli Studi di Napoli, Via A. Vivaldi 42, 81100 Caserta, Italy. Electronic address:

Adiponectin (Acrp30), its high molecular weight (HMW) oligomers, and Irisin are molecules involved in several metabolic processes. To investigate if these cytokines could represent new metabolic markers, we evaluated the expression of Acrp30 and Irisin in serum of obese children from South Italy affected by different degrees of insulin resistance (IR). The anthropometric and metabolic features were evaluated in 27 obese children versus 13 age-matched controls. The expression of Acrp30, its pattern and Irisin were investigated by ELISA, western blotting and fast protein liquid chromatography. The HOMA index was significantly higher in obese children versus controls, and metabolic syndrome was more prevalent in obese children with elevated IR versus those with normal HOMA (38% vs 16%). Total Acrp30 and HMW oligomers were significantly lower in obese than in control children, and the difference was more pronounced in children with HOMA >3.4. In control and obese children, total Acrp30 and HMW oligomers were inversely related to HOMA (r-0.38, p 0.02; r-0.35, p 0.03). Irisin was significantly higher in obese than in control children, and was inversely correlated with Acrp30 and HMW (r-0.32, p 0.04; r-0.39, p 0.01). The inverse correlation of Acpr30 and HMW oligomers with HOMA indicates that Acpr30 is directly involved in IR status. Moreover, the inverse correlation between Irisin and Acrp30 and, more significantly, between Irisin and HMW oligomers suggests that the two cytokines are closely connected. The use of Acrp30, HMW oligomers and Irisin as predictive factors of IR in obese children remains to be further elucidated.
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http://dx.doi.org/10.1016/j.cyto.2016.12.018DOI Listing
June 2017

β-Defensins in the Fight against Helicobacter pylori.

Molecules 2017 Mar 7;22(3). Epub 2017 Mar 7.

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II', 80131 Napoli, Italy.

Antimicrobial peptides (AMPs) play a pivotal role in the innate immune responses to Helicobacter pylori (Hp) in humans. β-Defensins, a class of cationic arginine-rich AMPs, are small peptides secreted by immune cells and epithelial cells that exert antimicrobial activity against a broad spectrum of microorganisms, including Gram-positive and Gram-negative bacteria and fungi. During Hp infections, AMP expression is able to eradicate the bacteria, thereby preventing Hp infections in gastrointestinal tract. It is likely that gastric β-defensins expression is increased during Hp infection. The aim of this review is to focus on increased knowledge of the role of β-defensins in response to Hp infection. We also briefly discuss the potential use of AMPs, either alone or in combination with conventional antibiotics, for the treatment of Hp infection.
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http://dx.doi.org/10.3390/molecules22030424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155297PMC
March 2017

The burden of obesity in asthma and COPD: Role of adiponectin.

Pulm Pharmacol Ther 2017 04 20;43:20-25. Epub 2017 Jan 20.

Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Seconda Università degli Studi di Napoli, via G. Vivaldi 42, 81100 Caserta, Italy; CEINGE-Biotecnologie Avanzate Scarl, via G. Salvatore 486, 80145 Napoli, Italy.

The influence of obesity on development, severity and prognosis of both asthma and COPD is attracting growing interest. The impact of obesity on the respiratory system ranges from structural modifications (decline of total lung capacity) to humoral alterations. Adipose tissue strongly contributes to the establishment of an inflammatory state being an important source of adipokines. Amongst adipokines, adiponectin is an important component of organ cross talk with adipose tissue exerting protective effects on a variety of pathophysiological processes. Adiponectin is secreted in serum where it abundantly circulates as complexes of different molecular weight. Adiponectin properties are mediated by specific receptors that are widely expressed with AdipoR1, AdipoR2, and T-cadherin being present on epithelial and endothelial pulmonary cells indicating a functional role on lung physiology. In COPD, mild to moderate obesity has been shown to have protective effects on patient's survival, while a higher mortality rate has been observed in patients with low BMI. A specific cluster of obese patients has been identified; in this group, asthma features are particularly severe and difficult to treat. Better understanding of the molecular mechanisms at the base of cross talk among different tissues and organs will lead to identification of new targets for both diagnosis and treatment of asthma and COPD.
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http://dx.doi.org/10.1016/j.pupt.2017.01.004DOI Listing
April 2017

Host defense peptide-derived privileged scaffolds for anti-infective drug discovery.

J Pept Sci 2017 Apr 12;23(4):303-310. Epub 2017 Jan 12.

CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145, Naples, Italy.

'Privileged scaffolds' are molecular frameworks which have been successfully exploited for small molecule drug discovery. Peptide privileged scaffolds, featuring a strictly conserved multiple-disulfide framework and high variability in the rest of the sequence, display a broad range of biological effects, including antimicrobial and antiviral activity. Unlike small molecules, however, the cost of manufacturing these peptides is high, and their synthesis challenging. We previously described a simplified privileged scaffold corresponding to the γ-core of human β-defensin-3 (HBD3). The γ-core is a common structural signature found in virtually all host defense peptides (HDPs) stabilized by multiple disulfides, and we showed that for HBD3, it represents the evolutionary starting point of the full-length molecule and, thus, is itself a primordial HDP. Accordingly, we showed that the peptide folded rapidly and was stable in human serum, and displayed many of the biological activities of HBD3. We report here that in addition to the previously reported antibacterial activity on planktonic bacteria, the γ-core peptide is active against biofilm formation and maturation. We also show that it is readily cell penetrant, like HBD3, although with a different mechanism, which is independent from CD98. Overall, the potency of the single-disulfide, 23-amino acid γ-core is comparable with the full-length peptide across the whole spectrum of examined properties, and the peptide is not toxic to human cells. The HBD3 γ-core peptide may therefore represent the first example of an economically viable lead peptide derived from a HDP privileged scaffold. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/psc.2962DOI Listing
April 2017
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