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Dietary habits strongly influence our health status, mostly in terms of maintenance of the inflammatory/anti-inflammatory homeostasis. High fat and high sugar diets account for the development of a low-grade inflammation, which is the pathogenic common denominator of various chronic diseases. Severe Acute Respiratory Syndrome Coronavirus (SARS)-CoV2 (COVID-19) infection affects all ages and especially frail elderly people and a nutritional intervention seems to be crucial in the course of this pandemic. The present review describes the properties of some vegetal products and their derivatives, such as Lupin sp., garlic, salvia and extra virgin olive oil (EVOO) that can be exploited for their beneficial effects, as preventive and/or nutritional treatment of coronavirus disease SARS-CoV2. Lupin, salvia, garlic and EVOO share overlapping properties, such as anti-oxidant, anti-inflammatory and anti-viral activities. Quite importantly, these products and their derivatives are able to recover the expression of angiotensin converting enzyme expression 2 on cell membrane, otherwise suppressed by COVID-19 binding and entry into cytoplasm. Dietary administration of the above nutraceuticals or their extracts may play a preventive or nutritional role in the course of SARS-CoV2 infection, even including the effects of the lockdown and the condition of inflamm-ageing.
Annalisa Rizzo; Raffaele L. Sciorsci; Thea Magrone; Emilio Jirillo. Exploitation of Some Natural Products for the Prevention and/or Nutritional Treatment of SARS-CoV2 Infection. Endocrine, Metabolic & Immune Disorders - Drug Targets 2021, 21, 1171 -1182.
AMA StyleAnnalisa Rizzo, Raffaele L. Sciorsci, Thea Magrone, Emilio Jirillo. Exploitation of Some Natural Products for the Prevention and/or Nutritional Treatment of SARS-CoV2 Infection. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021; 21 (7):1171-1182.
Chicago/Turabian StyleAnnalisa Rizzo; Raffaele L. Sciorsci; Thea Magrone; Emilio Jirillo. 2021. "Exploitation of Some Natural Products for the Prevention and/or Nutritional Treatment of SARS-CoV2 Infection." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. 7: 1171-1182.
Despite the evidence that plants do not possess sessile cells, they are able to mount a vigorous immune response against invaders or under stressful conditions. Plants are endowed with pattern recognition receptors (PPRs) which perceive damage-associated molecular patterns and microbe- associated molecular patterns or pathogen-associated molecular patterns (PAMPs), respectively. PPR activation leads to either the initiation of PAMP-triggered immunity (PTI) (early response) or the effector-triggered immunity (ETI). Both PTI and ETI contribute to plant systemic acquired resistance as an expression of immunological memory or trained immunity. PTI is initiated by activation of both receptor-like kinases and receptor-like proteins, while ETI depends on nucleotide- binding leucine-rich-repeat protein receptors for microbe recognition. Plant chloroplasts contribute to both PTI and ETI through the production of peptides, which act as hormones or phytocytokines. Salicylic acid, jasmonic acid and ethylene are the major compounds involved in plant defense. The interaction between plant receptors and/or their products and bacterial components will be discussed. Also, emphasis will be placed on plant microbiome for its contribution to plant immune response. Finally, the mutual interplay between insects and plants will also be illustrated. A better knowledge of plant immunity may pave the way for the exploitation of plant derivatives in the field of agriculture and medicine, as well.
Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets 2021, 21, 1183 -1195.
AMA StyleThea Magrone, Manrico Magrone, Matteo A. Russo, Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021; 21 (7):1183-1195.
Chicago/Turabian StyleThea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. 2021. "Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. 7: 1183-1195.
Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in the haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. The participation of platelets in inflammatory processes will also be discussed in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.
Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. Platelets: Angels and Demons Dancing on the Immune Stage. Nutrition Conducts the Orchestra. Endocrine, Metabolic & Immune Disorders - Drug Targets 2021, 21, 1196 -1218.
AMA StyleThea Magrone, Manrico Magrone, Matteo A. Russo, Emilio Jirillo. Platelets: Angels and Demons Dancing on the Immune Stage. Nutrition Conducts the Orchestra. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021; 21 (7):1196-1218.
Chicago/Turabian StyleThea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. 2021. "Platelets: Angels and Demons Dancing on the Immune Stage. Nutrition Conducts the Orchestra." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. 7: 1196-1218.
Background Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. Objective and methods To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: “sars cov 2”, “covid 19”, “subacute thyroiditis”, “atypical thyroiditis”, “chronic thyroiditis”, “hashimoto’s thyroiditis”, “graves’ disease”, “thyroid nodule”, “differentiated thyroid cancer”, “medullary thyroid cancer”, “methimazole”, “levothyroxine”, “multikinase inhibitor”, “remdesivir”, “tocilizumab”. Data were collected, analyzed, and discussed to answer the following clinical questions: “What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?”; “Could medical management of thyroid diseases influence the clinical course of COVID-19?”; “Does medical management of COVID-19 interfere with thyroid function?”; “Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?”. Results SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. Discussion Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.
G. Lisco; A. De Tullio; E. Jirillo; V. A. Giagulli; G. De Pergola; E. Guastamacchia; V. Triggiani. Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects. Journal of Endocrinological Investigation 2021, 44, 1801 -1814.
AMA StyleG. Lisco, A. De Tullio, E. Jirillo, V. A. Giagulli, G. De Pergola, E. Guastamacchia, V. Triggiani. Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects. Journal of Endocrinological Investigation. 2021; 44 (9):1801-1814.
Chicago/Turabian StyleG. Lisco; A. De Tullio; E. Jirillo; V. A. Giagulli; G. De Pergola; E. Guastamacchia; V. Triggiani. 2021. "Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects." Journal of Endocrinological Investigation 44, no. 9: 1801-1814.
Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce the release of proinflammatory cytokines and nitric oxide (NO), while increasing the levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Methods: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). The other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups, seven dropouts were recorded. Result: At T1 in comparison to T0, in treated patients, values of interferon-γ, IL-4, IL-17, pentraxin 3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo- treated patients, no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.
Thea Magrone; Emilio Jirillo; Manrico Magrone; Matteo A. Russo; Paolo Romita; Francesco Massari; Caterina Foti. Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis. Endocrine, Metabolic & Immune Disorders - Drug Targets 2021, 21, 374 -384.
AMA StyleThea Magrone, Emilio Jirillo, Manrico Magrone, Matteo A. Russo, Paolo Romita, Francesco Massari, Caterina Foti. Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021; 21 (2):374-384.
Chicago/Turabian StyleThea Magrone; Emilio Jirillo; Manrico Magrone; Matteo A. Russo; Paolo Romita; Francesco Massari; Caterina Foti. 2021. "Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. 2: 374-384.
Background: Plants have represented an essential source of foods for human beings, as confirmed by archeological studies that have revealed on old pottery the presence of proteins from cereal and legumes. Specific aims: In this review, major healthy effects derived from the consumption of plant fibers, polyunsaturated fatty acids (PUFAs) and polyphenols, respectively, will be described with special emphasis on their mechanisms of action, both at cellular and molecular levels. Dietary compounds: Fibers exhibit a prevalent prebiotic effect, acting on the intestinal microbiota with the production of protective metabolites, such as short chain fatty acids. Plant PUFAs include α-linolenic and stearidonic acids, which are precursors of other two major PUFAs, namely, eicosapentaenoic and docosahexaenoic acids. Some clinical trials demonstrated the ability of PUFAs to lower the risk of coronary disease, while other trials did not confirm such a finding. Polyphenols are endowed with anti-oxidant and anti-inflammatory activity in view of their property to inhibit NF-κB activation, to induce the anti-inflammatory T regulatory cells and to normalize the intestinal microbiota. The beneficial effects of polyphenols on obesity/diabetes, allergic/autoimmune and inflammatory disease are elucidated. Conclusion: Plants are one of the major sources of healthy dietary products, whose exploitation may promote prevention of chronic disease.
Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. Exploitation of Plant Natural Products for Preventing or Treating Human Disease. Second of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 21, 1 -16.
AMA StyleThea Magrone, Manrico Magrone, Matteo Antonio Russo, Emilio Jirillo. Taking Advantage of Plant Defense Mechanisms to Promote Human Health. Exploitation of Plant Natural Products for Preventing or Treating Human Disease. Second of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 21 ():1-16.
Chicago/Turabian StyleThea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. 2020. "Taking Advantage of Plant Defense Mechanisms to Promote Human Health. Exploitation of Plant Natural Products for Preventing or Treating Human Disease. Second of Two Parts." Endocrine, Metabolic & Immune Disorders - Drug Targets 21, no. : 1-16.
Background & Objectives: In old people, both innate and adaptive immune responses are impaired, thus leading to a condition of systemic inflamm-ageing, even including the involvement of the central nervous system (CNS). Aims: Here, main mechanisms of the immune ageing and neuro-inflammation will be discussed along with the dietary approaches for the modulation of age related diseases. Discussion: Neuroinflammation is caused by the passage of inflammatory mediators through the brain blood barrier to CNS. Then, in the brain, antigenic stimulation of microglia and/or its activation by peripheral cytokines lead to a robust production of free radicals with another wave of proinflammatory cytokines which, in turn, causes massive neuronal damage. Also, infiltrating T cells [T helper (h) and T cytotoxic cells] contribute to neuronal damage. Additionally, a peripheral imbalance between inflammatory Th17 cells and anti-inflammatory T regulatory cells seems to be prevalent in the aged brain, thus leading to a proinflammatory profile. Alzheimer’s disease, Parkinson’s disease and multiple sclerosis will be described as typical neurodegenerative diseases. Finally, modulation of the immune response thanks to the anti-oxidant and anti-inflammatory effects exerted by dietary products and nutraceuticals in ageing will be discussed. Special emphasis will be placed on polyunsaturated fatty acids, polyphenols, micronutrients and pre-probiotics and synbiotics. Conclusion: Ageing is characterized by an imbalance subversion of the immune system with a condition of inflamm-ageing. Neuroinflammation and neurodegenerative diseases seem to be a central manifestation of a peripheral perturbation of the immune machinery. Dietary products and nutraceuticals may lead to a down-regulation of the oxidative and pro-inflammatory profile in ageing.
Thea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 20, 1391 -1411.
AMA StyleThea Magrone, Manrico Magrone, Matteo A. Russo, Emilio Jirillo. Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20 (9):1391-1411.
Chicago/Turabian StyleThea Magrone; Manrico Magrone; Matteo A. Russo; Emilio Jirillo. 2020. "Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 9: 1391-1411.
Background: Heavy metals [arsenic, aluminium, cadmium, chromium, cobalt, lead, nickel (Ni), palladium and titanium] are environmental contaminants able to impact with host human cells, thus, leading to severe damage. Objective: In this review, the detrimental effects of several heavy metals on human organs will be discussed and special emphasis will be placed on Ni. In particular, Ni is able to interact with Toll-like receptor (TLR)-4 on immune and non immune cells, thus, triggering the cascade of pro-inflammatory cytokines. Then, inflammatory and allergic reactions mediated by Ni will be illustrated within different organs, even including the central nervous system, airways and the gastrointestinal system. Discussion: Different therapeutic strategies have been adopted to mitigate Ni-induced inflammatory-allergic reactions. In this context the ability of polyphenols to counteract the inflammatory pathway induced by Ni on peripheral blood leukocytes from Ni-sensitized patients will be outlined. In particular, polyphenols are able to decrease serum levels of interleukin (IL)-17, while increasing levels of IL-10. These data suggest that the equilibrium between T regulatory cells and T helper 17 cells is recovered with IL-10 acting as an anti-inflammatory cytokine. In the same context, polyphenols reduced elevated serum levels of nitric oxide, thus, expressing their anti-oxidant potential. Finally, the carcinogenic potential of heavy metals, even including Ni, will be highlighted. Conclusion: Heavy metals and, in particular, Ni are very spread in the environment. Nutritional approaches seem to represent a novel option in the treatment of Ni-induced damage and, among them, polyphenols should be taken into consideration for their anti-oxidant and anti-inflammatory activities.
Matteo Antonio Russo; Emilio Jirillo. Impact of heavy metals with host cells: Special focus on nickel-mediated pathologies and novel interventional approaches. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 20, 1 -1.
AMA StyleMatteo Antonio Russo, Emilio Jirillo. Impact of heavy metals with host cells: Special focus on nickel-mediated pathologies and novel interventional approaches. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20 (7):1-1.
Chicago/Turabian StyleMatteo Antonio Russo; Emilio Jirillo. 2020. "Impact of heavy metals with host cells: Special focus on nickel-mediated pathologies and novel interventional approaches." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 7: 1-1.
In this study, the neural phenotype is explored in rodent models of the spinocerebellar disorder known as the Friedreich Ataxia (FA), which results from mutations within the gene encoding the Frataxin mitochondrial protein. For this, the M12 line, bearing a targeted mutation, which disrupts the Frataxin gene exon 4 was used, together with the M02 line, which, in addition, is hemizygous for the human Frataxin gene mutation (Pook transgene), implying the occurrence of 82–190 GAA repeats within its first intron. The mutant mice phenotype was compared to the one of wild type littermates in regions undergoing differential profiles of neurogenesis, including the cerebellar cortex and the spinal cord by using neuronal (β-tubulin) and glial (Glial Fibrillary Acidic Protein) markers as well as the Contactin 1 axonal glycoprotein, involved in neurite growth control. Morphological/morphometric analyses revealed that while in Frataxin mutant mice the neuronal phenotype was significantly counteracted, a glial upregulation occurred at the same time. Furthermore, Contactin 1 downregulation suggested that changes in the underlying gene contributed to the disorder pathogenesis. Therefore, the FA phenotype implies an alteration of the developmental profile of neuronal and glial precursors. Finally, epigallocatechin gallate polyphenol administration counteracted the disorder, indicating protective effects of antioxidant administration.
Antonella Bizzoca; Martina Caracciolo; Patrizia Corsi; Thea Magrone; Emilio Jirillo; Gianfranco Gennarini. Molecular and Cellular Substrates for the Friedreich Ataxia. Significance of Contactin Expression and of Antioxidant Administration. Molecules 2020, 25, 4085 .
AMA StyleAntonella Bizzoca, Martina Caracciolo, Patrizia Corsi, Thea Magrone, Emilio Jirillo, Gianfranco Gennarini. Molecular and Cellular Substrates for the Friedreich Ataxia. Significance of Contactin Expression and of Antioxidant Administration. Molecules. 2020; 25 (18):4085.
Chicago/Turabian StyleAntonella Bizzoca; Martina Caracciolo; Patrizia Corsi; Thea Magrone; Emilio Jirillo; Gianfranco Gennarini. 2020. "Molecular and Cellular Substrates for the Friedreich Ataxia. Significance of Contactin Expression and of Antioxidant Administration." Molecules 25, no. 18: 4085.
Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1]. With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3]. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7]. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9]. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11]. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13]. In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies. In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16]. In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16]. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected. Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)- production in the course of SARS acting as IFN antagonist [20-22]. In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23]. In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25]. Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26]. As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27]. Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29]. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30]. In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31]. According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33]. These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19. Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34]. As recently reported, during COVID-19 pandemic in...
Manrico Magrone; Emilio Jirillo. Focus on Receptors for Coronaviruses with Special Reference to Angiotensin- Converting Enzyme 2 as a Potential Drug Target - A Perspective. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 20, 807 -811.
AMA StyleManrico Magrone, Emilio Jirillo. Focus on Receptors for Coronaviruses with Special Reference to Angiotensin- Converting Enzyme 2 as a Potential Drug Target - A Perspective. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20 (6):807-811.
Chicago/Turabian StyleManrico Magrone; Emilio Jirillo. 2020. "Focus on Receptors for Coronaviruses with Special Reference to Angiotensin- Converting Enzyme 2 as a Potential Drug Target - A Perspective." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 6: 807-811.
Background The novel severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) disease 2019 (COVID‐19) seems to have a worse clinical course among infected men compared with women, thus highlighting concerns about gender predisposition to serious prognosis. Therefore, androgens, particularly testosterone (T), could be suspected as playing a critical role in driving this excess of risk. However, gonadal function in critically ill men is actually unknown, mainly because serum T concentration is not routinely measured in clinical practice, even more in this clinical context. Objective To overview on possible mechanisms by which serum T levels could affect the progression of COVID‐19 in men. Methods Authors searched PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, Google, and institutional websites for medical subject headings terms and free text words referred to “SARS‐CoV‐2,” “COVID‐19,” “testosterone,” “male hypogonadism,” “gender” “immune system,” “obesity,” “thrombosis” until May 19th 2020. Results T, co‐regulating the expression of angiotensin‐converting enzyme 2 and transmembrane protease serine 2 in host cells, may facilitate SARS‐CoV‐2 internalization. Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation. Obesity, one of the leading causes of severe prognosis in infected patients, is strictly associated with functional hypogonadism, and may consistently strengthen the aforementioned alterations, ultimately predisposing to serious respiratory and systemic consequences. Discussion and conclusion T in comparison to estrogen may predispose men to a widespread COVID‐19 infection. Low serum levels of T, which should be supposed to characterize the hormonal milieu in seriously ill individuals, may predispose men, especially elderly men, to poor prognosis or death. Further studies are needed to confirm these pathophysiological assumptions and to promptly identify adequate therapeutic strategies.
Vito Angelo Giagulli; Edoardo Guastamacchia; Thea Magrone; Emilio Jirillo; Giuseppe Lisco; Giovanni De Pergola; Vincenzo Triggiani. Worse progression of COVID‐19 in men: Is testosterone a key factor? Andrology 2020, 9, 53 -64.
AMA StyleVito Angelo Giagulli, Edoardo Guastamacchia, Thea Magrone, Emilio Jirillo, Giuseppe Lisco, Giovanni De Pergola, Vincenzo Triggiani. Worse progression of COVID‐19 in men: Is testosterone a key factor? Andrology. 2020; 9 (1):53-64.
Chicago/Turabian StyleVito Angelo Giagulli; Edoardo Guastamacchia; Thea Magrone; Emilio Jirillo; Giuseppe Lisco; Giovanni De Pergola; Vincenzo Triggiani. 2020. "Worse progression of COVID‐19 in men: Is testosterone a key factor?" Andrology 9, no. 1: 53-64.
Mast cells (MCs) have recently been re-interpreted in the context of the immune scenario in the sense that their pro-allergic role is no longer exclusive. In fact, MCs even in steady state conditions maintain homeostatic functions, producing mediators and intensively cross-talking with other immune cells. Here, emphasis will be placed on the array of receptors expressed by MCs and the variety of cytokines they produce. Then, the bulk of data discussed will provide readers with a wealth of information on the dual ability of MCs not only to defend but also to offend the host. This double attitude of MCs relies on many variables, such as their subsets, tissues of residency and type of stimuli ranging from microbes to allergens and food antigens. Finally, the relationship between MCs with basophils and eosinophils will be discussed.
Thea Magrone; Emilio Jirillo; Manrico Magrone. Mast Cells as a Double-Edged Sword in Immunity: Their Function in Health and Disease. First of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 20, 654 -669.
AMA StyleThea Magrone, Emilio Jirillo, Manrico Magrone. Mast Cells as a Double-Edged Sword in Immunity: Their Function in Health and Disease. First of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20 (5):654-669.
Chicago/Turabian StyleThea Magrone; Emilio Jirillo; Manrico Magrone. 2020. "Mast Cells as a Double-Edged Sword in Immunity: Their Function in Health and Disease. First of Two Parts." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 5: 654-669.
: Mast cells (MCs) bear many receptors which allow them to respond tAs far as treatment of MC-derived diseases is concerned, allergen immunotherapy as well as other attempts to reduce MC-activation will be outlined according to the recent data. Finally, in agreement with current literature and our own data polyphenols have been demonstrated to attenuate type I allergic reactions and contact dermatitis in response to nickel. The use of polyphenols in these diseases will be discussed also in view of MC involvement.o a variety of exogenous and endogenous stimuli. However, MC function is dual since they can initiate pathological events or protect the host against infectious challenges. : The role of MCs in disease will be analyzed in a broad sense, describing cellular and molecular mechanisms related to their involvement in auto-inflammatory diseases, asthma, autoimmune diseases and cancer. On the other hand, their protective role in the course of bacterial, fungal and parasitic infections will also be illustrated. : Mast cells (MCs) bear many receptors that allow them to respond to a variety of exogenous and endogenous stimuli. However, MC function is dual since they can initiate pathological events or protect the host against infectious challenges.
Thea Magrone; Emilio Jirillo; Manrico Magrone. Mast Cells as a Double Edged Sword in Immunity: Disorders of Mast Cell Activation and Therapeutic Management. Second of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets 2020, 20, 670 -686.
AMA StyleThea Magrone, Emilio Jirillo, Manrico Magrone. Mast Cells as a Double Edged Sword in Immunity: Disorders of Mast Cell Activation and Therapeutic Management. Second of Two Parts. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20 (5):670-686.
Chicago/Turabian StyleThea Magrone; Emilio Jirillo; Manrico Magrone. 2020. "Mast Cells as a Double Edged Sword in Immunity: Disorders of Mast Cell Activation and Therapeutic Management. Second of Two Parts." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 5: 670-686.
In this review, special emphasis will be placed on red grape polyphenols for their antioxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of proinflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Additionally, the effects of red grape polyphenols will be analyzed in obesity, as a low-grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood–brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great antioxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites, and interaction with microbiota, deserve deeper studies.
Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies. Antioxidants 2019, 9, 35 .
AMA StyleThea Magrone, Manrico Magrone, Matteo Antonio Russo, Emilio Jirillo. Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies. Antioxidants. 2019; 9 (1):35.
Chicago/Turabian StyleThea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. 2019. "Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies." Antioxidants 9, no. 1: 35.
In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.
Thea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies. 2019, 1 .
AMA StyleThea Magrone, Manrico Magrone, Matteo Antonio Russo, Emilio Jirillo. Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies. . 2019; ():1.
Chicago/Turabian StyleThea Magrone; Manrico Magrone; Matteo Antonio Russo; Emilio Jirillo. 2019. "Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies." , no. : 1.
In mice, postnatal immune development has previously been investigated, and evidence of a delayed maturation of the adaptive immune response has been detected. In this study, the effects of red grape polyphenol oral administration on the murine immune response were explored using pregnant mice (TAG/F3 transgenic and wild type (wt) mice) as the animal model. The study was performed during pregnancy as well as during lactation until postnatal day 8. Suckling pups from polyphenol-administered dams as well as day 30 post-weaning pups (dietary-administered with polyphenols) were used. Polyphenol effects were evaluated, measuring splenic cytokine secretion. Phorbol myristate acetate-activated splenocytes underwent the highest cytokine production at day 30 in both wt and TAG/F3 mice. In the latter, release of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was found to be higher than in the wt counterpart. In this context, polyphenols exerted modulating activities on day 30 TAG/F3 mice, inducing release of interleukin (IL)-10 in hetero mice while abrogating release of IL-2, IFN-γ, TNF-α, IL-6, and IL-4 in homo and hetero mice. Polyphenols are able to prevent the development of an inflammatory/allergic profile in postnatal TAG/F3 mice.
Thea Magrone; Anna Spagnoletta; Antonella Bizzoca; Matteo Antonio Russo; Emilio Jirillo; Gianfranco Gennarini. Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice. Molecules 2019, 24, 2205 .
AMA StyleThea Magrone, Anna Spagnoletta, Antonella Bizzoca, Matteo Antonio Russo, Emilio Jirillo, Gianfranco Gennarini. Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice. Molecules. 2019; 24 (12):2205.
Chicago/Turabian StyleThea Magrone; Anna Spagnoletta; Antonella Bizzoca; Matteo Antonio Russo; Emilio Jirillo; Gianfranco Gennarini. 2019. "Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice." Molecules 24, no. 12: 2205.
Background and Objective: Hepatopancreas is an accessory organ associated with the liver in some fish, even including sea bass (Dicentrharcus labrax L.). Hepatopancreas contains an exocrine portion but until now its function has poorly been investigated. Methods: Here, European farmed sea bass have been treated with a feed enriched in polyphenols extracted from seeds of red grape (Nero di Troia cultivar) at two different doses (100 and 200 mg/kg, respectively) from day 273 to day 323. In fish samples, hepatopancreas area sizes have been measured to evaluate the effects of this dietary regimen on its morphology. Results: Quite interestingly, in treated fish area sizes of hepatopancreas were higher than those detected in untreated fish. Two hundred mg dose of polyphenols was more effective than that of 100 mg/kg polyphenols. Finally, hepatic polyphenol concentration was diminished in fish receiving 100 mg dose polyphenols and normalized with 200 mg dose in comparison to untreated fish. This evidence suggests the utilization of polyphenols for liver function, even including hepatopancreas development. Conclusion: Our data suggest an expansion of hepatopancreas induced by polyphenol administration that is also associated with less mortality in farmed fish.
Thea Magrone; Anna Spagnoletta; Manrico Magrone; Matteo Antonio Russo; Aldo Corriero; Emilio Jirillo; Letizia Passantino. Effects of Polyphenol Administration to European Farmed Sea Bass (Dicentrharcus labrax L.): Special Focus on Hepatopancreas Morphology. Endocrine, Metabolic & Immune Disorders - Drug Targets 2019, 19, 526 -533.
AMA StyleThea Magrone, Anna Spagnoletta, Manrico Magrone, Matteo Antonio Russo, Aldo Corriero, Emilio Jirillo, Letizia Passantino. Effects of Polyphenol Administration to European Farmed Sea Bass (Dicentrharcus labrax L.): Special Focus on Hepatopancreas Morphology. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2019; 19 (4):526-533.
Chicago/Turabian StyleThea Magrone; Anna Spagnoletta; Manrico Magrone; Matteo Antonio Russo; Aldo Corriero; Emilio Jirillo; Letizia Passantino. 2019. "Effects of Polyphenol Administration to European Farmed Sea Bass (Dicentrharcus labrax L.): Special Focus on Hepatopancreas Morphology." Endocrine, Metabolic & Immune Disorders - Drug Targets 19, no. 4: 526-533.
Background: T cell tolerance both at thymic and peripheral levels is a mechanism of protection finalized to eradicate autoreactive T cell clones and/or to maintain immune homeostasis, especially, postnatally. Central tolerance occurs in the thymic medulla via a mechanism of negative selection which leads to the eradication of autoreactive T cell clones. Mechanisms of Action: Such a tolerogenic event relies on Fas-mediated apoptosis of autoreactive T cell clones operated by thymic dendritic cells (DCs), on the one hand. On the other hand, activated thymic T regulatory (Treg) cells in cooperation with medullary thymic epithelial cells and DCs suppress autoreactive T cell clones. Peripherally, different types of Treg cells exert the so-called peripheral tolerance towards autoreactive T cell clones which may have escaped from negative selection mechanisms. At the same time, peripheral Treg cells activated by tolerogenic DC have antiinflammatory activities, especially in the intestine towards food and microbial antigens. Drug Targeting: Various natural and dietary products, such as vitamins (A, C, D), lactobacilli and polyphenols will be described for their tolerogenic capacity to attenuate the inflammatory pathway, as observed in preclinical and clinical studies.
Thea Magrone; Emilio Jirillo. The Tolerant Immune System: Biological Significance and Clinical Implications of T Cell Tolerance. Endocrine, Metabolic & Immune Disorders - Drug Targets 2019, 19, 580 -593.
AMA StyleThea Magrone, Emilio Jirillo. The Tolerant Immune System: Biological Significance and Clinical Implications of T Cell Tolerance. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2019; 19 (5):580-593.
Chicago/Turabian StyleThea Magrone; Emilio Jirillo. 2019. "The Tolerant Immune System: Biological Significance and Clinical Implications of T Cell Tolerance." Endocrine, Metabolic & Immune Disorders - Drug Targets 19, no. 5: 580-593.
Fish despite their low collocation in the vertebrate phylum possess a complete immune system. In teleost fish both innate and adaptive immune responses have been described with melanomacrophage centers (MMCs) equivalent to mammalian germinal centers. Primary lymphoid organs are represented by the thymus and kidney, while spleen and mucosa-associated lymphoid tissues act as secondary lymphoid organs. Functions of either innate immune cells (e.g., macrophages and dendritic cells) or adaptive immune cells (T and B lymphocytes) will be described in detail, even including their products, such as cytokines and antibodies. In spite of a robust immune arsenal, fish are very much exposed to infectious agents (marine bacteria, parasites, fungi, and viruses) and, consequentially, mortality is very much enhanced especially in farmed fish. In fact, in aquaculture stressful events (overcrowding), microbial infections very frequently lead to a high rate of mortality. With the aim to reduce mortality of farmed fish through the reinforcement of their immune status the current trend is to administer natural products together with the conventional feed. Then, in the second part of the present review emphasis will be placed on a series of products, such as prebiotics, probiotics and synbiotics, β-glucans, vitamins, fatty acids and polyphenols all used to feed farmed fish. With special reference to polyphenols, results of our group using red grape extracts to feed farmed European sea bass will be illustrated. In particular, determination of cytokine production at intestinal and splenic levels, areas of MMCs and development of hepatopancreas will represent the main biomarkers considered. All together, our own data and those of current literature suggests that natural product administration to farmed fish for their beneficial effects may, in part, solve the problem of fish mortality in aquaculture, enhancing their immune responses.
Thea Magrone; Matteo A. Russo; Emilio Jirillo. Dietary Approaches to Attain Fish Health with Special Reference to their Immune System. Current Pharmaceutical Design 2019, 24, 4921 -4931.
AMA StyleThea Magrone, Matteo A. Russo, Emilio Jirillo. Dietary Approaches to Attain Fish Health with Special Reference to their Immune System. Current Pharmaceutical Design. 2019; 24 (41):4921-4931.
Chicago/Turabian StyleThea Magrone; Matteo A. Russo; Emilio Jirillo. 2019. "Dietary Approaches to Attain Fish Health with Special Reference to their Immune System." Current Pharmaceutical Design 24, no. 41: 4921-4931.
Background:Secondary lymphoid organs (SLO) are distributed in many districts of the body and, especially, lymph nodes, spleen and gut-associated lymphoid tissue are the main cellular sites. On the other hand, tertiary lymphoid organs (TLO) are formed in response to inflammatory, infectious, autoimmune and neoplastic events. Developmental Studies: In the present review, emphasis will be placed on the developmental differences of SLO and TLO between small intestine and colon and on the role played by various chemokines and cell receptors. Undoubtedly, microbiota is indispensable for the formation of SLO and its absence leads to their poor formation, thus indicating its strict interaction with immune and non immune host cells. Furthermore, food antigens (for example, tryptophan derivatives, flavonoids and byphenils) bind the aryl hydrocarbon receptor on innate lymphoid cells (ILCs), thus promoting the development of postnatal lymphoid tissues. Also retinoic acid, a metabolite of vitamin A, contributes to SLO development during embryogenesis. Vitamin A deficiency seems to account for reduction of ILCs and scarce formation of solitary lymphoid tissue. Translational Studies: The role of lymphoid organs with special reference to intestinal TLO in the course of experimental and human disease will also be discussed. Future Perspectives: Finally, a new methodology, the so-called “gut-in-a dish”, which has facilitated the in vitro interaction study between microbe and intestinal immune cells, will be described.
Thea Magrone; Emilio Jirillo. Development and Organization of the Secondary and Tertiary Lymphoid Organs: Influence of Microbial and Food Antigens. Endocrine, Metabolic & Immune Disorders - Drug Targets 2019, 19, 128 -135.
AMA StyleThea Magrone, Emilio Jirillo. Development and Organization of the Secondary and Tertiary Lymphoid Organs: Influence of Microbial and Food Antigens. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2019; 19 (2):128-135.
Chicago/Turabian StyleThea Magrone; Emilio Jirillo. 2019. "Development and Organization of the Secondary and Tertiary Lymphoid Organs: Influence of Microbial and Food Antigens." Endocrine, Metabolic & Immune Disorders - Drug Targets 19, no. 2: 128-135.