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1.
Vitamin D Determinants, Status, and Antioxidant/Anti-inflammatory-Related Effects in Cardiovascular Risk and Disease: Not the Last Word in the Controversy.
Della Nera, G, Sabatino, L, Gaggini, M, Gorini, F, Vassalle, C
Antioxidants (Basel, Switzerland). 2023;(4)
Abstract
Beyond its key role in calcium homeostasis, vitamin D has been found to significantly affect the cardiovascular (CV) system. In fact, low vitamin D levels have been associated with increased CV risk, as well as increased CV morbidity and mortality. The majority of effects of this molecule are related directly or indirectly to its antioxidative and anti-inflammatory properties. Generally, vitamin D insufficiency is considered for 25-hydroxyvitamin D (25(OH)D) levels between 21-29 ng/mL (corresponding to 52.5-72.5 nmol/L), deficiency as 25(OH)D levels less than 20 ng/mL (<50 nmol/L), and extreme deficiency as 25(OH)D less than 10 ng/mL (<25 nmol/L). However, the definition of an optimal vitamin D status, as defined by 25(OH)D, remains controversial for many extra-bone conditions, including CV disease. In this review, confounding factors affecting the 25(OH)D measurement and status will be discussed. In particular, available evidence on the mechanism and role of vitamin D in relation to CV risk and disease through its antioxidant effect will be reported, also facing the aspect regarding the debate on the minimum blood 25(OH)D level required to ensure optimal CV health.
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2.
The impact of HCV chronic positivity and clearance on extrahepatic morbidity in thalassemia major patients: an observational study from MIOT Network.
Meloni, A, Pistoia, L, Gamberini, MR, Spasiano, A, Cuccia, L, Allò, M, Messina, G, Cecinati, V, Geraradi, C, Rosso, R, et al
European journal of internal medicine. 2023;:93-100
Abstract
BACKGROUND No study has evaluated the effect of hepatitis C virus (HCV) infection on the wide spectrum of complications affecting patients with thalassemia. OBJECTIVES This multicenter study prospectively assessed the relationship of HCV infection with diabetes mellitus and cardiovascular complications in patients with thalassemia major (TM). METHODS We considered 1057 TM patients (539 females; 29.79±10.08 years) enrolled in the MIOT Network and categorized into 4 groups: negative patients (group 1a, N=460), patients who spontaneously cleared the virus within 6months (group 1b, N=242), patients who eradicated the virus after the treatment with antiviral therapy (group 2, N=102), and patients with chronic HCV infection (group 3, N=254). RESULTS Group 1a and 1b were considered as a unique group (group 1). For both groups 1 and 3, a match 1:1 for age and sex with group 2 was performed. The effective study cohort consisted of 306 patients (three groups of 102 patients). During a mean follow-up of 67.93±39.20months, the group 3 experienced a significantly higher % increase/month in aspartate transaminase levels and left ventricular mass index than both groups 1 and 2. The changes in iron overload indexes were comparable among the three groups. Compared to group 1, the chronic HCV group showed a significantly higher risk of diabetes (hazard ratio-HR=5.33; p=0.043) and of cardiovascular diseases (HR=3.80; p=0.034). CONCLUSION Chronic HCV infection is associated with a significant higher risk of diabetes mellitus and cardiovascular complications in TM patients and should be approached as a systemic disease in which extrahepatic complications increase the weight of its pathological burden.
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3.
Sphingolipid Levels and Signaling via Resveratrol and Antioxidant Actions in Cardiometabolic Risk and Disease.
Gaggini, M, Fenizia, S, Vassalle, C
Antioxidants (Basel, Switzerland). 2023;(5)
Abstract
Resveratrol (RSV) is a phenolic compound with strong antioxidant activity, which is generally associated with the beneficial effects of wine on human health. All resveratrol-mediated benefits exerted on different systems and pathophysiological conditions are possible through resveratrol's interactions with different biological targets, along with its involvement in several key cellular pathways affecting cardiometabolic (CM) health. With regard to its role in oxidative stress, RSV exerts its antioxidant activity not only as a free radical scavenger but also by increasing the activity of antioxidant enzymes and regulating redox genes, nitric oxide bioavailability and mitochondrial function. Moreover, several studies have demonstrated that some RSV effects are mediated by changes in sphingolipids, a class of biolipids involved in a number of cellular functions (e.g., apoptosis, cell proliferation, oxidative stress and inflammation) that have attracted interest as emerging critical determinants of CM risk and disease. Accordingly, this review aimed to discuss the available data regarding the effects of RSV on sphingolipid metabolism and signaling in CM risk and disease, focusing on oxidative stress/inflammatory-related aspects, and the clinical implications of this relationship.
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4.
Interplay between Vitamin D and Sphingolipids in Cardiometabolic Diseases.
Fenizia, S, Gaggini, M, Vassalle, C
International journal of molecular sciences. 2023;(23)
Abstract
Sphingolipids (SLs) are structural, bioactive molecules with several key cellular roles, whereas 1,25-dihydroxyvitamin D (1,25(OH)D), the active form of vitamin D, is considered the major regulator of calcium homeostasis, although it also exerts other extraskeletal effects. Many studies reported the physiological connection between vitamin D and SLs, highlighting not only the effects of vitamin D on SL metabolism and signaling but also the influence of SLs on vitamin D levels and function, thus strongly suggesting a crosstalk between these molecules. After a brief description of 1,25(OH)D and SL metabolism, this review aims to discuss the preclinical and clinical evidence on the crosstalk between SLs and 1,25(OH)D, with a special focus on cardiometabolic diseases.
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5.
Selenium and Selenoproteins at the Intersection of Type 2 Diabetes and Thyroid Pathophysiology.
Gorini, F, Vassalle, C
Antioxidants (Basel, Switzerland). 2022;(6)
Abstract
Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of T2D pathogenesis and progression. Selenium is considered an essential element with antioxidant properties, and is incorporated into the selenoproteins involved in the antioxidant response. Furthermore, deiodinases, the enzymes responsible for homeostasis and for controlling the activity of thyroid hormones (THs), contain Se. Given the crucial action of oxidative stress in the onset of insulin resistance (IR) and T2D, and the close connection between THs and glucose metabolism, Se may be involved in these fundamental relationships; it may cover a dual role, both as a protective factor and as a risk factor of T2D, depending on its basal plasma concentration and the individual's diet intake. In this review we discuss the current evidence (from experimental, observational and randomized clinical studies) on how Se is associated with the occurrence of T2D and its influence on the relationship between thyroid pathophysiology, IR and T2D.
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6.
Thyroid Dysfunction and COVID-19: The Emerging Role of Selenium in This Intermingled Relationship.
Gorini, F, Sabatino, L, Coi, A, Iervasi, G, Vassalle, C
International journal of environmental research and public health. 2022;(11)
Abstract
COVID-19 represents a worldwide public health emergency, and, beyond the respiratory symptoms characterizing the classic viral disease, growing evidence has highlighted a possible reciprocal relationship between SARS-CoV-2 infection and thyroid dysfunction. The updated data discussed in this review suggests a role of SARS-CoV-2 infection on the thyroid gland, with multiple thyroid pictures described. Conversely, no conclusion can be drawn on the association between pre-existing thyroid disease and increased risk of SARS-CoV-2 infection. In this scenario, selenium (Se), an essential trace element critical for thyroid function and known as an effective agent against viral infections, is emerging as a potential novel therapeutic option for the treatment of COVID-19. Large multicentre cohort studies are required to elucidate the mechanisms underlying thyroid dysfunction during or following recovery from COVID-19, including Se status. Meanwhile, clinical trials should be performed to evaluate whether adequate intake of Se can help address COVID-19 in Se-deficient patients, also avoiding thyroid complications that can contribute to worsening outcomes during infection.
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7.
Vitamin D Status in Children with Autism Spectrum Disorders: Determinants and Effects of the Response to Probiotic Supplementation.
Guiducci, L, Vassalle, C, Prosperi, M, Santocchi, E, Morales, MA, Muratori, F, Calderoni, S
Metabolites. 2022;(7)
Abstract
A relationship between the presence of clinical symptoms and gastrointestinal (GI) disturbances associated with nutritional deficiencies, including vitamin D (25(OH)D) deficiency, has been observed in autism spectrum disorder (ASD). The aim was to evaluate 25(OH)D levels according to the annual rhythm cycle, gender, the severity of autism, nutritional or clinical status, inflammatory and metabolic biomarkers, GI symptoms, and the clinical response to probiotic/placebo supplementation in preschooler children with ASD. Eighty-one ASD preschoolers (67 males) were assessed with standardized tools for ASD severity (ADOS score) and GI symptoms (by GI-Index at six-items and at nine-items, the latter defined as the Total GI-Index). The 25(OH)D levels were compared among different ASD subgroups according to metabolic and inflammatory biomarkers (leptin, insulin, resistin, PAI-1, MCP-1, TNF-alfa, and IL-6), gender, and the presence or absence of: (i) GI symptoms, (ii) the response to probiotic supplementation (the improvement of GI symptomatology), (iii) the response to probiotic supplementation (improvement of ASD severity). Only 25% of the ASD children presented an adequate 25(OH)D status (≥30 ng/mL according to the Endocrine Society guidelines). All the 25(OH)D levels falling in the severe deficiency range (<10 ng/mL) were observed in the male subgroup. A significant inverse correlation between 25(OH)D and leptin was observed (R = −0.24, p = 0.037). An inverse correlation was found between 25(OH)D levels and the GI Index 6-Items and Total GI-Index (R = −0.25, p = 0.026; −0.27, = 0.009) and a direct relationship with the probiotic response (R = 0.4, p = 0.05). The monitoring of 25(OH)D levels and the co-administration of 25(OH)D and probiotic supplementation could be considered in ASD from early ages.
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8.
Lipids in Atherosclerosis: Pathophysiology and the Role of Calculated Lipid Indices in Assessing Cardiovascular Risk in Patients with Hyperlipidemia.
Gaggini, M, Gorini, F, Vassalle, C
International journal of molecular sciences. 2022;(1)
Abstract
The role of lipids is essential in any phase of the atherosclerotic process, which is considered a chronic lipid-related and inflammatory condition. The traditional lipid profile (including the evaluation of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) is a well-established tool to assess the risk of atherosclerosis and as such has been widely used as a pillar of cardiovascular disease prevention and as a target of pharmacological treatments in clinical practice over the last decades. However, other non-traditional lipids have emerged as possible alternative predictors of cardiometabolic risk in addition to traditional single or panel lipids, as they better reflect the overall interaction between lipid/lipoprotein fractions. Therefore, this review deals with the lipid involvement characterizing the pathophysiology of atherosclerosis, discussing some recently proposed non-traditional lipid indices and, in the light of available knowledge, their actual potential as new additive tools to better stratify cardiovascular risk in patients with hyperlipidemia as well as possible therapeutic targets in the clinical practice.
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9.
Vitamin D, Thyroid Hormones and Cardiovascular Risk: Exploring the Components of This Novel Disease Triangle.
Vassalle, C, Parlanti, A, Pingitore, A, Berti, S, Iervasi, G, Sabatino, L
Frontiers in physiology. 2021;:722912
Abstract
The role of thyroid hormones (THs) in the cardiovascular (CV) system, through several direct and indirect effects is recognized. Even very small modification in TH levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome) may adversely affect the CV system, whereas thyroid hormones benefit the CV system and improve the prognosis. There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity, renin-angiotensin-aldosterone system, nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement. Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression causing subsequential peripheral conversion of T4 into T3. However, the functional links among THs, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed. The main aim of this review is to discuss pathophysiology of this relationship, proposing new mechanistic insights involving vitamin D in the modulation of cardiometabolic disease and thyroid profile.
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10.
H2S as a Bridge Linking Inflammation, Oxidative Stress and Endothelial Biology: A Possible Defense in the Fight against SARS-CoV-2 Infection?
Gorini, F, Del Turco, S, Sabatino, L, Gaggini, M, Vassalle, C
Biomedicines. 2021;(9)
Abstract
The endothelium controls vascular homeostasis through a delicate balance between secretion of vasodilators and vasoconstrictors. The loss of physiological homeostasis leads to endothelial dysfunction, for which inflammatory events represent critical determinants. In this context, therapeutic approaches targeting inflammation-related vascular injury may help for the treatment of cardiovascular disease and a multitude of other conditions related to endothelium dysfunction, including COVID-19. In recent years, within the complexity of the inflammatory scenario related to loss of vessel integrity, hydrogen sulfide (H2S) has aroused great interest due to its importance in different signaling pathways at the endothelial level. In this review, we discuss the effects of H2S, a molecule which has been reported to demonstrate anti-inflammatory activity, in addition to many other biological functions related to endothelium and sulfur-drugs as new possible therapeutic options in diseases involving vascular pathobiology, such as in SARS-CoV-2 infection.