Publications by authors named "Sebastiano Gangemi"

203 Publications

The PREdictor of MAlnutrition in Systemic Sclerosis (PREMASS) Score: A Combined Index to Predict 12 Months Onset of Malnutrition in Systemic Sclerosis.

Front Med (Lausanne) 2021 17;8:651748. Epub 2021 Mar 17.

National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), Leeds Teaching Hospitals National Health Service (NHS) Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.

Malnutrition is a severe complication in Systemic Sclerosis (SSc) and it is associated with significant mortality. Notwithstanding, there is no defined screening or clinical pathway for patients, which is hampering effective management and limiting the opportunity for early intervention. Here we aim to identify a combined index predictive of malnutrition at 12 months using clinical data and specific serum adipokines. This was an international, multicentre observational study involving 159 SSc patients in two independent discovery ( = 98) and validation ( = 61) cohorts. Besides routine clinical and serum data at baseline and 12 months, Malnutrition Universal Screening Tool (MUST) score and serum concentration of leptin and adiponectin were measured for each participant at baseline. The endpoint of malnutrition was defined according to European Society of Clinical Nutrition and Metabolism (ESPEN) recommendation. Significant parameters from univariate analysis were tested in logistic regression analysis to identify the predictive index of malnutrition in the derivation cohort. The onset of malnutrition at 12 months correlated with adiponectin, leptin and their ratio (A/L), MUST, clinical subset, disease duration, Scl70 and Forced Vital Capaciy (FVC). Logistic regression analysis defined the formula: -2.13 + (A/L0.45) + (Scl700.28) as the best PREdictor of MAlnutrition in SSc (PREMASS) (AUC = 0.96; 95% CI 0.93, 0.99). PREMASS < -1.46 had a positive predictive value (PPV) > 62% and negative predictive value (NPV) > 97% for malnutrition at 12 months. PREMASS is a feasible index which has shown very good performance in two independent cohorts for predicting malnutrition at 12 months in SSc. The implementation of PREMASS could aid both in clinical management and clinical trial stratification/enrichment to target malnutrition in SSc.
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http://dx.doi.org/10.3389/fmed.2021.651748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010181PMC
March 2021

IL-33 in Mental Disorders.

Medicina (Kaunas) 2021 Mar 26;57(4). Epub 2021 Mar 26.

School and Operative Unit of Allergy and Clinical Immunology, Policlinico "G. Martino", Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Mental disorders are common in the general population; every year about 25% of the total European population is affected by a mental condition. The prevalence of psychiatric disorders might be underestimated. Emerging evidence highlights the role of immune response as a key factor in MDs. Immunological biomarkers seem to be related to illness progression and to treatment effectiveness; several studies suggest strong associations among IL-6, TNFa, S100b, IL 1b, and PCR with affective or schizophrenic disorders. The purpose of this review is to examine and to understand the possible link between mental disorders and interleukin 33 to clarify the role of this axis in the immune system. We found 13 research papers that evaluated interleukin 33 or interleukin 31 levels in subjects affected by mental disorders. Eight studies investigated cytokines in affective disorders. Three studies measured levels of IL-33 in schizophrenia and two studies focused on patients affected by autism spectrum disorders. Alterations in brain structure and neurodevelopmental outcome are affected by multiple levels of organization. Disorders of the autoimmune response, and of the IL-33/31 axis, may therefore be one of the factors involved in this process. These results support the evidence that alarmins, particularly the IL-33/31 axis, need more consideration among researchers and practitioners.
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http://dx.doi.org/10.3390/medicina57040315DOI Listing
March 2021

A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes.

Antioxidants (Basel) 2021 Mar 30;10(4). Epub 2021 Mar 30.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy.

Parkinson's disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD.
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http://dx.doi.org/10.3390/antiox10040539DOI Listing
March 2021

Nutraceuticals against Oxidative Stress in Autoimmune Disorders.

Antioxidants (Basel) 2021 Feb 8;10(2). Epub 2021 Feb 8.

Department of Clinical and Experimental Medicine, Unit and School of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy.

Antioxidant mechanisms are constituted of enzymes, endogenous, and non-enzymatic, exogenous, which have the role of counterbalancing oxidative stress. Intake of these compounds occurs in the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids which are called "phytochemicals". Most of these substances are responsible for the positive properties of fruits and vegetables, which are an essential part of a healthy life with roles in ameliorating chronic illnesses and favoring longevity. Nutraceuticals are substances contained in a food or fragment of it influencing health with positive effects on health helping in precenting or treating disorders. We conducted a review illustrating the principal applications of nutraceuticals in autoimmune disorders. Literature reported several studies about exogenous dietary antioxidant supplementation in diverse autoimmune diseases such as rheumatoid arthritis, lupus, diabetes, and multiple sclerosis. In these pathologies, promising results were obtained in some cases. Positive outcomes were generally associated with a reduction of oxidative stress parameters and a boost to antioxidant systems, and sometimes with anti-inflammatory effects. The administration of exogenous substances through food derivates or dietary supplements following scientific standardization was demonstrated to be effective. Further bias-free and extended studies should be conducted that include ever-increasing oxidative stress biomarkers.
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http://dx.doi.org/10.3390/antiox10020261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914737PMC
February 2021

IL-33/Vitamin D Crosstalk in Psoriasis-Associated Osteoporosis.

Front Immunol 2020 8;11:604055. Epub 2021 Jan 8.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Patients with psoriasis (Pso) and, in particular, psoriatic arthritis (PsoA) have an increased risk of developing osteoporosis (OP). It has been shown that OP is among the more common pathologies associated with Pso, mainly due to the well-known osteopenizing conditions coexisting in these patients. Pso and OP share common risk factors, such as vitamin D deficiency and chronic inflammation. Interestingly, the interleukin (IL)-33/ST2 axis, together with vitamin D, is closely related to both Pso and OP. Vitamin D and the IL-33/ST2 signaling pathways are closely involved in bone remodeling, as well as in skin barrier pathophysiology. The production of anti-osteoclastogenic cytokines, e.g., IL-4 and IL-10, is promoted by IL-33 and vitamin D, which are stimulators of both regulatory and Th2 cells. IL-33, together with other Th2 cytokines, shifts osteoclast precursor differentiation towards macrophage and dendritic cells and inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis by regulating the expression of anti-osteoclastic genes. However, while the vitamin D protective functions in OP and Pso have been definitively ascertained, the overall effect of IL-33 on bone and skin homeostasis, because of its pleiotropic action, is still controversial. Emerging evidence suggests a functional link between vitamin D and the IL-33/ST2 axis, which acts through hormonal influences and immune-mediated effects, as well as cellular and metabolic functions. Based on the actions of vitamin D and IL-33 in Pso and OP, here, we hypothesize the role of their crosstalk in the pathogenesis of both these pathologies.
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http://dx.doi.org/10.3389/fimmu.2020.604055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819870PMC
January 2021

Involvement of RAGE and Oxidative Stress in Inflammatory and Infectious Skin Diseases.

Antioxidants (Basel) 2021 Jan 9;10(1). Epub 2021 Jan 9.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria-Gazzi, 98125 Messina, Italy.

The surface receptor for advanced glycosylation end-products (RAGE) and its soluble (sRAGE) and endogenous secretory (EN-RAGE) forms belong to the superfamily of toll-like receptors and play important roles in inflammation and autoimmunity, directly or through binding with advanced glycosylation end-products (AGE) and advanced oxidation protein products (AOPP). We reviewed the literature on the role of RAGE in skin diseases. Research in this field is still rather limited (28 articles) but suggests the involvement of RAGE and RAGE-related pathways in chronic inflammatory diseases (lupus, psoriasis, atopic dermatitis, and lichen planus), infectious diseases (leprosy, -induced skin lesions), alterations of the repairing processes in diabetic skin, systemic sclerosis, and ulcers. These data prompt further research in this field, which not only will be useful to better understand the pathogenetic mechanisms of diseases, but is also likely to have intriguing clinical implications. Indeed, when their role in the complex and multifactorial inflammatory balance will be adequately defined, RAGE and related molecules could be used as markers of disease severity and/or response to treatment. Moreover, future promising therapeutic perspectives could be topical administration of some of these molecules (e.g., sRAGE) to modulate local inflammatory response and/or the development of anti-RAGE antibodies for systemic treatment.
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http://dx.doi.org/10.3390/antiox10010082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827747PMC
January 2021

Antiproliferative Effects of St. John's Wort, Its Derivatives, and Other Species in Hematologic Malignancies.

Int J Mol Sci 2020 Dec 25;22(1). Epub 2020 Dec 25.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

is a widely present plant, and extracts of its leaves, flowers, and aerial elements have been employed for many years as therapeutic cures for depression, skin wounds, and respiratory and inflammatory disorders. also displays an ample variety of other biological actions, such as hypotensive, analgesic, anti-infective, anti-oxidant, and spasmolytic abilities. However, recent investigations highlighted that this species could be advantageous for the cure of other pathological situations, such as trigeminal neuralgia, as well as in the treatment of cancer. This review focuses on the in vitro and in vivo antitumor effects of St. John's Wort ( its derivatives, and other species in hematologic malignancies. induces apoptosis in both myeloid and lymphoid cells. Other targets include matrix metalloproteinase-2, vascular endothelial growth factor, and matrix metalloproteinase-9, which are mediators of cell migration and angiogenesis. also downregulates the expression of proteins that are involved in the resistance of leukemia cells to chemotherapeutic agents. Finally, and its derivatives appear to have photodynamic effects and are candidates for applications in tumor photodynamic therapy. Although the in vitro studies appear promising, controlled in vivo studies are necessary before we can hypothesize the introduction of and its derivatives into clinical practice for the treatment of hematologic malignancies.
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http://dx.doi.org/10.3390/ijms22010146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795730PMC
December 2020

The Impact of Immunological Checkpoint Inhibitors and Targeted Therapy on Chronic Pruritus in Cancer Patients.

Biomedicines 2020 Dec 22;9(1). Epub 2020 Dec 22.

School of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Although pruritus may sometimes be a consequential situation to neoplasms, it more frequently emerges after commencing chemotherapy. In this review, we present our analysis of the chemotherapy treatments that most often induce skin changes and itching. After discussing conventional chemotherapies capable of inducing pruritus, we present our evaluation of new drugs such as immunological checkpoint inhibitors (ICIs), tyrosine kinase inhibitors, and monoclonal antibodies. Although ICIs and targeted therapy are thought to damage tumor cells, these therapies can modify homeostatic events of the epidermis and dermis, causing the occurrence of cutaneous toxicities in treated subjects. In the face of greater efficacy, greater skin toxicity has been reported for most of these drugs. A remarkable aspect of some reports is the presence of a probable correlation between cutaneous toxicity and treatment effectiveness in tumor patients who were treated with novel drugs such as nivolumab or pembrolizumab. Findings from these experiments demonstrate that the occurrence of any grade of skin side effects can be considered as a predictor of a better outcome. In the near future, studies on the relationship between the onset of skin alterations and outcomes could open new perspectives on the treatment of neoplasms through specific target therapy.
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http://dx.doi.org/10.3390/biomedicines9010002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822170PMC
December 2020

The Osteoporosis/Microbiota Linkage: The Role of miRNA.

Int J Mol Sci 2020 Nov 24;21(23). Epub 2020 Nov 24.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.
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http://dx.doi.org/10.3390/ijms21238887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727697PMC
November 2020

Pain Biomarkers in Cancer: An Overview.

Curr Pharm Des 2021 ;27(2):293-304

IRCCS Centro Neurolesi Bonino- Pulejo, Messina, Italy.

Background: Pain is a common symptom in oncologic patients and its management is generally guided with reference to pain individually perceived by patients and expressed through self-reported scales. However, the utility of these tools is limited as it strongly depends on patients' opinions. For this reason, more objective instruments are desirable.

Objective: In this overview, scientific articles indicating potential markers to be used for pain management in cancer were collected and discussed.

Methods: Research was performed on principal electronic scientific databases by using the words "pain", "cancer", "markers" and "biomarkers" as the main keywords, and findings describing potential biomarkers for the management of cancer pain were reported.

Results: Studies on pain markers not specific for cancer typology (inflammatory, genetic markers predicting response to analgesic drugs, neuroimaging markers) and pain markers for specific types of cancer (bone cancer, breast cancer, lung cancer, head and neck cancer, prostate cancer, cancer in pediatrics) have been presented and commented on.

Conclusion: This overview supports the view of the involvement of inflammatory mediators in the mechanisms underlying cancer pain. Only a small amount of data from research up till today is available on markers that can help in the management of pain, except for pro-inflammatory cytokines and other inflammatory indexes such as C-reactive protein (CRP). However, biomarkers are a promising strategy useful to predict pain intensity and to objectively quantify analgesic response in guiding decisions regarding individual-tailored treatments for cancer patients.
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http://dx.doi.org/10.2174/1381612826666201102103520DOI Listing
January 2021

Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR-ABL-Negative Myeloproliferative Neoplasm.

Antioxidants (Basel) 2020 Oct 23;9(11). Epub 2020 Oct 23.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have recently been revealed to be related to chronic inflammation, oxidative stress, and the accumulation of reactive oxygen species. It has been proposed that MPNs represent a human inflammation model for tumor advancement, in which long-lasting inflammation serves as the driving element from early tumor stage (over polycythemia vera) to the later myelofibrotic cancer stage. It has been theorized that the starting event for acquired stem cell alteration may occur after a chronic inflammation stimulus with consequent myelopoietic drive, producing a genetic stem cell insult. When this occurs, the clone itself constantly produces inflammatory components in the bone marrow; these elements further cause clonal expansion. In --negative MPNs, the driver mutations include , , and . Transcriptomic studies of hematopoietic stem cells from subjects with driver mutations have demonstrated the upregulation of inflammation-related genes capable of provoking the development of an inflammatory state. The possibility of acting on the inflammatory state as a therapeutic approach in MPNs appears promising, in which an intervention operating on the pathways that control the synthesis of cytokines and oxidative stress could be effective in reducing the possibility of leukemic progression and onset of complications.
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http://dx.doi.org/10.3390/antiox9111037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690801PMC
October 2020

Involvement of miR-142 and miR-155 in Non-Infectious Complications of CVID.

Molecules 2020 Oct 16;25(20). Epub 2020 Oct 16.

Operative Unit and School of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Background And Objectives: Common variable immunodeficiency (CVID) is the most prevalent antibody impairment. It is characterized by failure in immunoglobulin and protective antibody generation and defined by an increased tendency toward bacterial infections, autoimmunity, and malignancy. Most CVID diagnoses do not follow a classical Mendelian pattern of inheritance. In recent years, CVID has been considered an epigenetic phenomenon in the majority of cases, overtaking previous monogenetic and/or polygenetic theories. The aim of this study was to review the role of microRNAs (miRNAs) in CVID, focusing on the involvement of the same miRNAs in various non-infectious clinical complications of CVID, mainly autoimmunity and/or cancer.

Materials And Methods: A bibliographic search of the scientific literature was carried out independently by two researchers in scientific databases and search engines. The MeSH terms "microRNAs" and "common variable immunodeficiency" were used. All research articles from inception to May 2020 were considered.

Results: The literature data showed the involvement of two miRNAs in primary immunodeficiency: miR-142 and miR-155. Both of these miRNAs have been investigated through mice models, in which miR-142 and miR-155 were deleted. These knock-out (KO) mice models showed phenotypic analogies to CVID patients with hypogammaglobulinemia, adaptive immunodeficiency, polyclonal proliferation, lung disease, and enteric inflammation. miR-142 and miR-155 have been found to be involved in the following autoimmune and neoplastic clinical complications of CVID: Gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, natural killer/Tcell lymphoma (NKTCL), and immune thrombocytopenia.

Conclusions: miR-142 and miR-155 deregulation leads to similar CVID phenotypesin KO mice models. Although no data are available on the involvement of these miRNAs in human CVID, their dysregulation has been detected in human CVID comorbidities. The literature data show that miRNA sequences in murine models are comparable to those in humans; therefore, miR-142 and miR-155 involvement in human CVID could be hypothesized.
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http://dx.doi.org/10.3390/molecules25204760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587593PMC
October 2020

Oxidative stress as a key feature of autoimmune thyroiditis: an update.

Minerva Endocrinol 2020 Dec 24;45(4):326-344. Epub 2020 Sep 24.

Unit of Allergology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Introduction: Oxidative stress has been proposed as one of the factors concurring in the pathophysiology of autoimmune thyroid diseases. Reactive oxygen species are the main expression of oxidative stress in biological systems, and their production can overcome antioxidant defenses ultimately leading to cell damage, apoptosis, and death. The present review was aimed at describing the state of the art of the relationships between oxidative stress and autoimmune thyroiditis. The most used biomarkers of oxidative stress and their correlation with thyroid function are reported.

Evidence Acquisition: We conducted a search of the literature in the English language starting from 2000, using the following search terms: "Hashimoto thyroiditis," "autoimmune thyroiditis," "hypothyroidism," "hyperthyroidism," "oxidative stress," "oxidants," "antioxidant," "advanced glycation end products." Both clinical studies and animal models were evaluated.

Evidence Synthesis: Data form clinical studies clearly indicate that the balance between oxidants and antioxidants is shifted towards the oxidative side in patients with autoimmune thyroiditis, suggesting that oxidative stress may be a key event in the pathophysiology of the disease, irrespective of thyroid function. Studies in animal models, such as the NOD.H2h4 mouse, confirm that thyroidal accumulation of ROS plays a role in the initiation and progression of autoimmune thyroiditis.

Conclusions: Oxidant/antioxidant imbalance represent a key feature of thyroid autoimmunity. Oxidative stress parameters could be used as biochemical markers of chronic inflammation, to better predict the disease evolution along its natural history. Dietary habits and antioxidant supplements may provide protection from autoimmunity, opening new perspectives in the development of more tailored therapies.
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http://dx.doi.org/10.23736/S0391-1977.20.03268-XDOI Listing
December 2020

S100B in heart diseases.

Cardiovasc Pathol 2020 Nov - Dec;49:107235. Epub 2020 Jun 25.

School and Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University Hospital of Messina "G. Martino", University of Messina, Messina, Italy.

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http://dx.doi.org/10.1016/j.carpath.2020.107235DOI Listing
November 2020

AntagomiRs: A novel therapeutic strategy for challenging COVID-19 cytokine storm.

Cytokine Growth Factor Rev 2021 04 9;58:111-113. Epub 2020 Sep 9.

Institute of Clinical Physiology, National Research Council of Italy (IFC-CNR), Via Moruzzi 1, 56124, Pisa, Italy. Electronic address:

Is it possible to develop a reliable, safe treatment for the widespread COVID-19 pandemic shortly? COVID-19 is characterized by a disruptive cytokine storm, quickly and often irreversibly damaging the patient's lungs, as its main target organ, leading to lung failure and death. Actual experimental therapies are trying to reduce the activation of some specific cytokines, such as IL-6, somewhat reducing the burden for the patient. However, they are often unable to block the whole storm occurring at the cytokine level. In presence of the cytokine storm, especially in severe patients, antagomiRs, already demonstrated to be efficient and secure in cardiovascular disease, could represent a useful alternative to such treatment, customizable upon the disease specificities and applicable to other coronaviruses possibly associated with such clinical manifestations, while a reliable, efficient vaccine is being distributed.
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http://dx.doi.org/10.1016/j.cytogfr.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480641PMC
April 2021

Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors.

Clin Mol Allergy 2020 3;18:16. Epub 2020 Sep 3.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Tranexamic acid (TXA) is a synthetic lysine analogue that is well known as antifibrinolytic agent. It can reduce blood loss in clinical use, especially in conditions where fibrinolysis or hyperfibrinolysis are involved, such as trauma or surgery. Moreover, TXA has been approved as second-line prophylactic therapy for hereditary angioedema and further data have been published about a possible use of TXA as maintenance treatment for nonhistaminergic angioedema and treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors. TXA can be administered through several routes: orally, topically, or intravenously. Although, it is a drug with a very high safety profile, in few cases hypersensitivity reactions have been described occurring with different clinical manifestations. Ethamsylate can be an alternative in TXA sensitized patients. In this brief article we describe TXA adverse reactions and current protocols which have been proposed to help clinicians to diagnose TXA hypersensitivity.
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http://dx.doi.org/10.1186/s12948-020-00131-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473809PMC
September 2020

The role of skin and gut microbiome and epigenetic modifications upon skin autoimmune disorders.

Curr Mol Med 2020 Aug 12. Epub 2020 Aug 12.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina. Italy.

Human microbiota and immune system are strictly connected to each other. Several studies demonstrated that normal skin and/or gut floral alterations may have negative consequences upon disease pathogenesis. Indeed, a strong association between skin and gut microbiota alterations and autoimmune diseases was found. Moreover, a significant interplay between microbiome and miRNAs expression was noticed among several conditions. The aim of this review article is to shed new light on some of the commonest skin disorders such as psoriasis, atopic dermatitis, allergic contact dermatitis, with special regards to epigenetic pathogenetic mechanisms such as miRNAs expression and skin and gut microbiome alterations. Indeed, evidence is still lacking regarding these two factors and their possible interactions. We believe their implications may be crucial for screening, early diagnosis and also therapeutic strategies, therefore this field could represent a promising challenge for further studies.
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http://dx.doi.org/10.2174/1566524020666200812222324DOI Listing
August 2020

Role of Alarmins in the Pathogenesis of Systemic Sclerosis.

Int J Mol Sci 2020 Jul 15;21(14). Epub 2020 Jul 15.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy.

Systemic sclerosis (SSc) is a rare chronic autoimmune disease associated with significant morbidity and mortality. Two main subsets of SSc are recognized: (i) diffuse cutaneous SSc with rapidly progressive fibrosis of the skin, lungs, and other internal organs; and (ii) limited cutaneous SSc, which is dominated by vascular manifestations, with skin and organ fibrosis generally limited and slowly progressing. In spite of intense investigation, both etiology and pathogenesis of SSc are still unknown. Genetic and environmental factors, as well as abnormalities of immune functions, are strongly suggested for etiology, while microvascular abnormalities, immune system activation, and oxidative stress are suggested for the pathogenesis. Recently, it has been found that a multitude of mediators and cytokines are implicated in the fibrotic processes observed in SSc. Among these, a central role could be exerted by "alarmins", endogenous and constitutively expressed proteins/peptides that function as an intercellular signal defense. This review describes, in a detailed manner, the role of alarmins in the pathogenesis of scleroderma.
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http://dx.doi.org/10.3390/ijms21144985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404317PMC
July 2020

Immunopathology of SARS-CoV-2 Infection: Immune Cells and Mediators, Prognostic Factors, and Immune-Therapeutic Implications.

Int J Mol Sci 2020 Jul 6;21(13). Epub 2020 Jul 6.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

The present is a comprehensive review of the immunopathology of Covid-19. The immune reaction to SARS-CoV-2 infection is characterized by differentiation and proliferation of a variety of immune cells with immune mediator production and release, and activation of other pathogen resistance mechanisms. We fully address the humoral and cellular immune changes induced by the virus, with particular emphasis on the role of the "cytokine storm" in the evolution of the disease. Moreover, we also propose some immune alterations (i.e., inflammatory parameters, cytokines, leukocytes and lymphocyte subpopulations) as prognostic markers of the disease. Furthermore, we discuss how immune modifying drugs, such as tocilizumab, chloroquine, glucocorticoids and immunoglobulins, and blood purification therapy, can constitute a fundamental moment in the therapy of the infection. Finally, we made a critical analysis of a number of substances, not yet utilized, but potentially useful in SARS-CoV-2 patients, such as IFN lambda, TNF blockers, ulinastatin, siponimod, tacrolimus, mesenchymal stem cells, inhibitors of mononuclear macrophage recruitment, IL-1 family antagonists, JAK-2 or STAT-3 inhibitors.
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http://dx.doi.org/10.3390/ijms21134782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370171PMC
July 2020

Rich at risk: socio-economic drivers of COVID-19 pandemic spread.

Clin Mol Allergy 2020 1;18:12. Epub 2020 Jul 1.

Institute of Clinical Physiology, National Research Council of Italy (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy.

COVID-19, the novel coronavirus affecting the most part of worldwide countries since early 2020, is fast increasing its prevalence around the world, representing a significant emergency for the population and the health systems at large. While proper treatments are being developed, in-depth studies concerning its way of diffusion are necessary, in order to understand how the virus is actually spreading, through the investigation on some socio-economic indicators for the various countries in the world, retrieved through open-access data publicly available. The correlation analysis displayed significant relationships between COVID-19 incidence with several of such indicators, including the Gross Domestic Product per capita and the number of flights per capita, whereas mortality is mainly related to the main age of the population. All such data displayed an interesting mean to understand the way the virus has diffused worldwide, possibly representing the basis for future preventive measures to effectively challenge a new COVID-19 pandemic wave, but also other, similar pandemics.
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http://dx.doi.org/10.1186/s12948-020-00127-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327192PMC
July 2020

Detecting Collagen Molecules at Picogram Level through Electric Field-Induced Accumulation.

Sensors (Basel) 2020 Jun 24;20(12). Epub 2020 Jun 24.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy.

The demand for sensors capable of measuring low-abundant collagen in human fluids has highly increased in recent years. Indeed, collagen is expected to be a biomarker for chronic diseases and could monitor their progression. Here we show detection of highly diluted samples of collagen at picogram level thanks to an innovative pyro-electrohydrodynamic jet (p-jet) system. Through the intense electric fields generated by the pyroelectric effect in a ferroelectric crystal, the collagen solution was concentrated on a small area of a slide that was appropriately functionalized to bind proteins. The collagen molecules were labeled by an appropriate fluorophore to show how the number of tiny droplets influences the limit of detection of the technique. The results show that the p-jet is extremely promising for overcoming the current detection limits of collagen-based products in human fluids, performing 10 times better than the enzyme-linked immunosorbent assay (ELISA) and thus paving the way for the early diagnosis of related chronic diseases.
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http://dx.doi.org/10.3390/s20123567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349194PMC
June 2020

Atopic dermatitis severity during exposure to air pollutants and weather changes with an Artificial Neural Network (ANN) analysis.

Pediatr Allergy Immunol 2020 11 20;31(8):938-945. Epub 2020 Aug 20.

School and Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Background: Epidemiological studies have shown an association between global warming, air pollution, and allergic diseases. Several air pollutants, including volatile organic compounds, formaldehyde, toluene, nitrogen dioxide (NO ), and particulate matter, act as risk factors for the development or aggravation of atopic dermatitis (AD). We evaluated the impact of air pollutants and weather changes on AD patients.

Materials And Methods: Sixty AD patients ≥5 years of age (mean age: 23.5 ± 12.5 years), living in the Campania Region (Southern Italy), were followed for 18 months. The primary outcome was the effect of atmospheric and climatic factors on signs and symptoms of AD, assessed using the SCORAD (SCORing Atopic Dermatitis) index. We measured mean daily temperature (TOD), outdoor relative humidity (RH), diurnal temperature range (DTR), precipitation, particulate with aerodynamic diameter ≤ 10 μm (PM ), NO , tropospheric ozone (O ), and total pollen count (TPC). A multivariate logistic regression analysis was used to examine the associations of AD signs and symptoms with these factors. An artificial neural network (ANN) analysis investigated the relationships between weather changes, environmental pollutants, and AD severity.

Results: The severity of AD symptoms was positively correlated with outdoor temperatures (TOD, DTR), RH, precipitation, PM , NO , O , and TPC. The ANN analysis also showed a good discrimination performance (75.46%) in predicting disease severity based on environmental pollution data, but weather-related factors were less predictive.

Conclusion: The results of the present study provide evidence that weather changes and air pollutions have a significant impact on skin reactivity and symptoms in AD patients, increasing the severity of the dermatitis. The knowledge of the single variables proportion on AD severity symptoms is important to propose alerts for exacerbations in patients with AD of each age. This finding represents a good starting point for further future research in an area of increasingly growing interest.
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http://dx.doi.org/10.1111/pai.13314DOI Listing
November 2020

Cancer and SARS-CoV-2 Infection: Diagnostic and Therapeutic Challenges.

Cancers (Basel) 2020 Jun 15;12(6). Epub 2020 Jun 15.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

In late December 2019, a new infectious viral disease appeared. A new betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), has been recognized as the pathogen responsible for this infection. Patients affected by tumors are more vulnerable to infection owing to poor health status, concomitant chronic diseases, and immunosuppressive conditions provoked by both the cancer and antitumor therapies. In this review, we have analyzed some lesser known aspects of the relationship between neoplasms and SARS-CoV-2 infection, starting from the different expression of the ACE2 receptor of the virus in the various neoplastic pathologies, and the roles that different cytokine patterns could have in vulnerability to infection and the appearance of complications. This review also reports the rationale for a possible use of drugs commonly employed in neoplastic therapy, such as bevacizumab, ibrutinib, selinexor, thalidomide, carfilzomib, and PD-1 inhibitors, for the treatment of SARS-CoV-2 infection. Finally, we have highlighted some diagnostic challenges in the recognition of SARS-CoV-2 infection in cancer-infected patients. The combination of these two health problems-tumors and a pandemic virus-could become a catastrophe if not correctly handled. Careful and judicious management of cancer patients with SARS-Cov-2 could support a better outcome for these patients during the current pandemic.
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http://dx.doi.org/10.3390/cancers12061581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352319PMC
June 2020

Anticancer Activity of L.: Mechanisms of Action and Therapeutic Potentials.

Nutrients 2020 Jun 10;12(6). Epub 2020 Jun 10.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Alternative treatments for neoplastic diseases with new drugs are necessary because the clinical effectiveness of chemotherapy is often reduced by collateral effects. Several natural substances of plant origin have been demonstrated to be successful in the prevention and treatment of numerous tumors. L. is a herb that is cultivated in diverse areas of the world. There is increasing attention being directed towards the pharmaceutical capacities of rosemary, utilized for its anti-inflammatory, anti-infective or anticancer action. The antitumor effect of rosemary has been related to diverse mechanisms, such as the antioxidant effect, antiangiogenic properties, epigenetic actions, regulation of the immune response and anti-inflammatory response, modification of specific metabolic pathways, and increased expression of onco-suppressor genes. In this review, we aim to report the results of preclinical studies dealing with the anticancer effects of rosemary, the molecular mechanisms related to these actions, and the interactions between rosemary and anticancer drugs. The prospect of utilizing rosemary as an agent in the treatment of different neoplastic diseases is discussed. However, although the use of rosemary in the therapy of neoplasms constitutes a fascinating field of study, large and controlled studies must be conducted to definitively clarify the real impact of this substance in clinical practice.
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http://dx.doi.org/10.3390/nu12061739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352773PMC
June 2020

Oxidative Stress and Photodynamic Therapy of Skin Cancers: Mechanisms, Challenges and Promising Developments.

Antioxidants (Basel) 2020 May 22;9(5). Epub 2020 May 22.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Ultraviolet radiation is one of the most pervasive environmental interactions with humans. Chronic ultraviolet irradiation increases the danger of skin carcinogenesis. Probably, oxidative stress is the most important mechanism by which ultraviolet radiation implements its damaging effects on normal cells. However, notwithstanding the data referring to the negative effects exerted by light radiation and oxidative stress on carcinogenesis, both factors are used in the treatment of skin cancer. Photodynamic therapy (PDT) consists of the administration of a photosensitiser, which undergoes excitation after suitable irradiation emitted from a light source and generates reactive oxygen species. Oxidative stress causes a condition in which cellular components, including DNA, proteins, and lipids, are oxidised and injured. Antitumor effects result from the combination of direct tumour cell photodamage, the destruction of tumour vasculature and the activation of an immune response. In this review, we report the data present in literature dealing with the main signalling molecular pathways modified by oxidative stress after photodynamic therapy to target skin cancer cells. Moreover, we describe the progress made in the design of anti-skin cancer photosensitisers, and the new possibilities of increasing the efficacy of PDT via the use of molecules capable of developing a synergistic antineoplastic action.
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http://dx.doi.org/10.3390/antiox9050448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278813PMC
May 2020

Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology.

Clin Mol Allergy 2020 6;18. Epub 2020 May 6.

5Section of Dermatology, Department of Medicine, University of Perugia, Perugia, Italy.

Background: Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12-22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6-16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1-1.5 cases/1000 inhabitants/year.

Methods: We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria.

Conclusions: The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.
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http://dx.doi.org/10.1186/s12948-020-00123-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201804PMC
May 2020

Jellyfish anaphylaxis: A wide spectrum of sensitization routes.

Allergy Asthma Proc 2020 05;41(3):158-166

From the School and Division of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy, and the.

Recent studies demonstrated that, in the past few years, the number of jellyfish species is increasing worldwide; this increase can be explained by environmental and climatic reasons. Contacts with jellyfish can cause acute and chronic effects, including allergic reactions. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing as well as marine sports and job activities represent important risk factors that can increase the probability of sensitization. Recently, it was also pointed out the possibility of anaphylaxis caused by jellyfish ingestion. In these cases, the sensitization could also be related to previous stings. In cases in which there is no history of jellyfish contact or ingestion, it has been hypothesized that there is a sensitization to an unknown cross-reactive antigen. The purpose of this work was to collect and review published studies and cases of anaphylaxis associated with jellyfish. We performed a medical literature data base search, which included English language articles published until September 2019, by using the key words "jellyfish" associated with "anaphylaxis" or "anaphylactic shock." The results of our research showed that dangerous reactions can be caused both by contact and ingestion. Moreover, the latest changes in food habits, life style, and globalization could lead to a more frequent exposure to jellyfish both by contact and ingestion, and, consequently, to a higher probability of sensitization. Prospective studies and well-structured research are needed to better understand all the potential immunologic elements of jellyfish, to clarify its role in sensitization, and to avoid possible dangerous allergic reactions caused by cross-reactivity.
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http://dx.doi.org/10.2500/aap.2020.41.200014DOI Listing
May 2020

Neuroprotective Effect of Bergamot Juice in 6-OHDA-Induced SH-SY5Y Cell Death, an Model of Parkinson's Disease.

Pharmaceutics 2020 Apr 5;12(4). Epub 2020 Apr 5.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina 98100, Italy.

Much evidence suggests that both oxidative stress and apoptosis play a key role in the pathogenesis of Parkinson's disease (PD). The present study aims to evaluate the protective effect of bergamot juice (BJ) against 6-hydroxydopamine (6-OHDA)- or HO-induced cell death. Treatment of differentiated SH-SY5Y human neuroblastoma cells with 6-OHDA or HO resulted in cell death that was significantly reduced by the pre-treatment with BJ. The protective effects of BJ seem to correlate with the reduction of intracellular reactive oxygen species and nitric oxide generation caused by 6-OHDA or HO. BJ also attenuated mitochondrial dysfunction, caspase-3 activation, imbalance of pro- and anti-apoptotic proteins, MAPKs activation and reduced NF-ĸB nuclear translocation evoked by neurotoxic agents. Additionally, BJ exhibited excellent antioxidant capability in assays. Collectively, our results suggest that BJ exerts neuroprotective effect through the interplay with specific cell targets and its antioxidant activity, making it worthy of consideration for the management of neurodegenerative diseases.
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http://dx.doi.org/10.3390/pharmaceutics12040326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238189PMC
April 2020

Interactions between the MicroRNAs and Microbiota in Cancer Development: Roles and Therapeutic Opportunities.

Cancers (Basel) 2020 Mar 27;12(4). Epub 2020 Mar 27.

Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

The human microbiota is made up of the fungi, bacteria, protozoa and viruses cohabiting within the human body. An altered microbiota can provoke diseases such as cancer. The mechanisms by which a modified microbiota can intervene in the onset and progression of neoplastic diseases are manifold. For instance, these include the effects on the immune system and the onset of obesity. A different mechanism seems to be constituted by the continuous and bidirectional relationships existing between microbiota and miRNAs. MiRNAs emerged as a novel group of small endogenous non-coding RNAs from that control gene expression. Several works seem to confirm the presence of a close connection between microbiota and miRNAs. Although the main literature data concern the correlations between microbiota, miRNAs and colon cancer, several researches have revealed the presence of connections with other types of tumour, including the ovarian tumour, cervical carcinoma, hepatic carcinoma, neoplastic pathologies of the central nervous system and the possible implication of the microbiota-miRNAs system on the response to the treatment of neoplastic pathologies. In this review, we summarise the physiological and pathological functions of the microbiota on cancer onset by governing miRNA production. A better knowledge of the bidirectional relationships existing between microbiota and miRNAs could provide new markers for the diagnosis, staging and monitoring of cancer and seems to be a promising approach for antagomir-guided approaches as therapeutic agents.
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http://dx.doi.org/10.3390/cancers12040805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225936PMC
March 2020

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review.

Medicina (Kaunas) 2020 Mar 19;56(3). Epub 2020 Mar 19.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy.

Alarmins are endogenous mediators released by cells following insults or cell death to alert the host's innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiological processes and inflammatory diseases including osteoporosis. The aim of the review was to evaluate the role of alarmins in osteoporosis. A bibliographic search of the published scientific literature regarding the role of alarmins in osteoporosis was organized independently by two researchers in the following scientific databases: Pubmed, Scopus, and Web of Science. The keywords used were combined as follows: "alarmins and osteoporosis", "RAGE and osteoporosis", "HMGB1 and osteoporosis", "IL-1 and osteoporosis", "IL 33 and osteopororsis", "S100s protein and osteoporosis". The information was summarized and organized in the present review. We highlight the emerging roles of alarmins in various bone remodeling processes involved in the onset and development of osteoporosis, as well as their potential role as biomarkers of osteoporosis severity and progression. Findings of the research suggest a potential use of alarmins as pharmacological targets in future therapeutic strategies aimed at preventing bone loss and fragility fractures induced by aging and inflammatory diseases.
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http://dx.doi.org/10.3390/medicina56030138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142770PMC
March 2020