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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 Role of Consumption of Molybdenum Biofortified Crops in Bone Homeostasis and Healthy Aging.
Vasto, S, Baldassano, D, Sabatino, L, Caldarella, R, Di Rosa, L, Baldassano, S
Nutrients. 2023;(4)
Abstract
Osteoporosis is a chronic disease and public health issue in aging populations. Inadequate intake of micronutrients increases the risk of bone loss during an adult's lifespan and therefore of osteoporosis. The aim of the study was to analyze the effects of consumption of biofortified crops with the micronutrient molybdenum (Mo) on bone remodeling and metabolism in a population of adults and seniors. The trial enrolled 42 senior and 42 adult people randomly divided into three groups that consumed lettuce biofortified with molybdenum (Mo-biofortified group) or without biofortification (control group) or molybdenum in a tablet (Mo-tablet group) for 12 days. We chose an experimental period of 12 days because the bone remodeling marker levels are influenced in the short term. Therefore, a period of 12 days allows us to determine if there are changes in the indicators. Blood samples, obtained at time zero and at the end of the study, were compared within the groups adults and seniors for the markers of bone resorption, C-terminal telopeptide (CTX) and bone formation osteocalcin, along with the markers of bone metabolism, parathyroid hormone (PTH), calcitonin, albumin-adjusted calcium, vitamin D, phosphate and potassium. Consumption of a Mo tablet did not affect bone metabolism in the study. Consumption of Mo-biofortified lettuce significantly reduced levels of CTX and PTH and increased vitamin D in adults and seniors while levels of osteocalcin, calcitonin, calcium, potassium and phosphate were not affected. The study opens up new considerations about the role of nutrition and supplementation in the prevention of chronic diseases in middle-aged and older adults. Consumption of Mo-biofortified lettuce positively impacts bone metabolism in middle-aged and older adults through reduced bone resorption and improved bone metabolism while supplementation of Mo tablets did not affect bone remodeling or metabolism. Therefore, Mo-biofortified lettuce may be used as a nutrition intervention to improve bone homeostasis and prevent the occurrence of osteoporosis in the elderly.
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3.
Boosting plant food polyphenol concentration by saline eustress as supplement strategies for the prevention of metabolic syndrome: an example of randomized interventional trial in the adult population.
Ferrantelli, V, Vasto, S, Alongi, A, Sabatino, L, Baldassano, D, Caldarella, R, Gagliano, R, Di Rosa, L, Consentino, BB, Vultaggio, L, et al
Frontiers in nutrition. 2023;:1288064
Abstract
INTRODUCTION Phenolic compounds in lettuce can increase by the application of positive stress (eustress) such as moderate saline stress. Phenolic compounds possess antioxidant capacity that is a key factor in the detoxification of excess reactive oxygen species. A double-blinded randomized interventional and placebo- controlled study design was carried out to compare the effect of daily dietary eustress lettuce ingestion in hepatic, lipid, bone, glucose, and iron metabolism. METHODS Forty-two healthy volunteers, 19 female and 23 male participants, were divided into two groups. Participants were randomized into a polyphenol-enriched treatment (PET) arm or control arm. Each arm consumed 100 g/day of control or eustress (polyphenols enriched treatment = PET) lettuce for 12 days. Primary study outcomes were serological analysis for assessing hepatic, lipid, bone, iron, and glucose markers at baseline and after 12 days. Secondary outcomes assessed body composition. RESULTS Salinity stress reduced plant yield but increased caffeic acid (+467%), chlorogenic acid (+320%), quercetin (+538%), and rutin (+1,095%) concentrations. The intake of PET lettuce reduced PTH, low-density lipoprotein (LDL), cholesterol, alanine transaminase (ALT), and aspartate transaminase (AST) enzyme levels and increased vitamin D and phosphate levels, while iron and glucose metabolism were unaffected. DISCUSSION Supplementation with eustress lettuce by increasing polyphenols concentration ameliorates hepatic, lipid, and bone homeostasis. Body composition was not affected. CLINICAL TRIAL REGISTRATION https://classic.clinicaltrials.gov/ct2/show/NCT06002672, identifier: NCT06002672.
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4.
Genetic Mechanisms for Hybrid Breeding in Vegetable Crops.
Singh, H, Sekhon, BS, Kumar, P, Dhall, RK, Devi, R, Dhillon, TS, Sharma, S, Khar, A, Yadav, RK, Tomar, BS, et al
Plants (Basel, Switzerland). 2023;(12)
Abstract
To address the complex challenges faced by our planet such as rapidly changing climate patterns, food and nutritional insecurities, and the escalating world population, the development of hybrid vegetable crops is imperative. Vegetable hybrids could effectively mitigate the above-mentioned fundamental challenges in numerous countries. Utilizing genetic mechanisms to create hybrids not only reduces costs but also holds significant practical implications, particularly in streamlining hybrid seed production. These mechanisms encompass self-incompatibility (SI), male sterility, and gynoecism. The present comprehensive review is primarily focused on the elucidation of fundamental processes associated with floral characteristics, the genetic regulation of floral traits, pollen biology, and development. Specific attention is given to the mechanisms for masculinizing and feminizing cucurbits to facilitate hybrid seed production as well as the hybridization approaches used in the biofortification of vegetable crops. Furthermore, this review provides valuable insights into recent biotechnological advancements and their future utilization for developing the genetic systems of major vegetable crops.
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5.
SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis.
Pranzini, E, Pardella, E, Muccillo, L, Leo, A, Nesi, I, Santi, A, Parri, M, Zhang, T, Uribe, AH, Lottini, T, et al
Cell reports. 2022;(7):111233
Abstract
5-Fluorouracil (5-FU) is a key component of chemotherapy for colorectal cancer (CRC). 5-FU efficacy is established by intracellular levels of folate cofactors and DNA damage repair strategies. However, drug resistance still represents a major challenge. Here, we report that alterations in serine metabolism affect 5-FU sensitivity in in vitro and in vivo CRC models. In particular, 5-FU-resistant CRC cells display a strong serine dependency achieved either by upregulating endogenous serine synthesis or increasing exogenous serine uptake. Importantly, regardless of the serine feeder strategy, serine hydroxymethyltransferase-2 (SHMT2)-driven compartmentalization of one-carbon metabolism inside the mitochondria represents a specific adaptation of resistant cells to support purine biosynthesis and potentiate DNA damage response. Interfering with serine availability or affecting its mitochondrial metabolism revert 5-FU resistance. These data disclose a relevant mechanism of mitochondrial serine use supporting 5-FU resistance in CRC and provide perspectives for therapeutic approaches.
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6.
A New Potential Dietary Approach to Supply Micronutrients to Physically Active People through Consumption of Biofortified Vegetables.
Baldassano, S, Polizzi, MR, Sabatino, L, Caldarella, R, Macaluso, A, Alongi, A, Caldara, GF, Ferrantelli, V, Vasto, S
Nutrients. 2022;(14)
Abstract
Micronutrients are required in many reactions involved in physical activity and exercise. Most physically active people do not meet the body's needs in terms of micronutrients through diet. The novelty of the present manuscript is the use of an innovative dietary approach to supply micronutrients to physically active people through biofortified food. Therefore, the key point of this study was to verify whether supplementation with biofortified vegetables-and specifically molybdenum (Mo)-enriched lettuce-in healthy volunteers affects essential regulators of body homeostasis and, specifically, hematological parameters, iron and lipid metabolism, and hepatic function. Twenty-four healthy volunteers were allocated in a double-blinded manner to either a control group that consumed lettuce, or the intervention group, which consumed Mo-enriched lettuce, for 12 days. Blood samples were collected at baseline (T0) and after 12 days (T1). We found that supplementation with Mo-enriched lettuce did not affect hematological parameters, liver function, or lipid metabolism, but significantly improved iron homeostasis by increasing non-binding hemoglobin iron by about 37% and transferrin saturation by about 42%, while proteins of iron metabolism (e.g., transferrin, ferritin, ceruloplasmin) were not affected. The serum molybdenum concentration increased by about 42%. In conclusion, this study shows that consumption of Mo-biofortified lettuce ameliorates iron homeostasis in healthy subjects, and suggests that it could be used as a new nutritional supplementation strategy to avoid iron deficiency in physically active people.
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7.
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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8.
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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9.
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.
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10.
Topical Ectoine: A Promising Molecule in the Upper Airways Inflammation-A Systematic Review.
Casale, M, Moffa, A, Carbone, S, Fraccaroli, F, Costantino, A, Sabatino, L, Lopez, MA, Baptista, P, Cassano, M, Rinaldi, V
BioMed research international. 2019;:7150942
Abstract
To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the mucosa of the upper airways (UA). Recently, topical administration of ectoine has just been recognized as adjuvant treatment in the Allergic Rhinitis (AR) and Rhinosinusitis (ARS). The aim of this work is to review the published literature regarding all the potential therapeutic effects of ectoine in the acute and chronic inflammatory diseases of UA. Pertinent studies published without temporal limitation were selected searching on MEDLINE the following terms: "ectoine" and "nasal spray," "oral spray," "upper respiratory tract infections," "rhinosinusitis," "rhinitis," "rhinoconjunctivitis," "pharyngitis," and "laryngitis." At the end of our selection process, six relevant publications were included: two studies about the effect of ectoine on AR, one study about ARS, one study about rhinitis sicca anterior, and two studies about acute pharyngitis and/or laryngitis. Due to its moisturizing and anti-inflammatory properties, topical administration of ectoine could play a potential additional role in treatment of acute and chronic inflammatory diseases of UA, in particular in the management of sinonasal conditions improving symptoms and endoscopic findings. However, these results should be viewed cautiously as they are based on a limited number of studies; some of them were probably underpowered because of their small patient samples.