Age and Gender-related Variations of Molecular and Phenotypic Parameters in A Cohort of Sicilian Population: from Young to Centenarians

People are living longer, but lifespan increase does not coincide with a boost in health-span. Thus, improving the quality of life of older people is a priority. Centenarians reach extreme longevity in a relatively good health status, escaping or delaying fatal or strongly invalidating diseases. Therefore, studying processes involved in longevity is important to explain the biological mechanisms of health and well-being, since knowledge born from this approach can provide valuable information on how to slow aging. We performed the present study in a well characterized very homogeneous sample of 173 people from Western Sicily, to update existing literature on some phenotypic aspects of aging…

Autoimmune diseases and 8.1 ancestral haplotype: an update

The aim of the present review is to provide an update of the current research into the pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype. This is a common Caucasoid haplotype carried by most people who type for HLA-B8, DR3. Numerous genetic studies reported that individuals with certain HLA alleles have a higher risk of specific autoimmune disorders than those without these alleles. However, much remains to be learned about the heritability of autoimmune conditions. Recently, progress and advances in the field of genome-wide-association studies have revolutionized the capacity to perform large, economically feasible, and statistically robust analyses of HLA within …

Klotho and vitamin D in multiple sclerosis: an Italian study

Introduction Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D3 levels, and multiple sclerosis (both …

COVID-19 and Alzheimer’s Disease

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a neurotropic virus with a high neuroinvasive potential. Indeed, more than one-third of patients develop neurological symptoms, including confusion, headache, and hypogeusia/ageusia. However, long-term neurological consequences have received little interest compared to respiratory, cardiovascular, and renal manifestations. Several mechanisms have been proposed to explain the potential SARS-CoV-2 neurological injury that could lead to the development of neurodegenerative diseases, including Alzheimer’s Disease (AD). A mutualistic relationship between AD and COVID-19 seems to exist. On the one hand, COVID-19 patients seem to …

Targeting aging with functional food: Pasta with opuntia single-arm pilot study

Interventions to extend life span represent the new perspective in aging investigation. Healthy dietary habits are important modifiable factors that can favor a healthy aging phenotype. Many studies have demonstrated benefits for metabolic syndrome and type 2 diabetes mellitus resulting from the traditional Mediterranean foods. Opuntia Ficus Indica (OFI), widespread in the Mediterranean basin, belongs to the Cactaceae family. It is known for its antioxidant and anti-inflammatory properties. Moreover, products containing extracts from OFI fruits or cladodes have been used to control obesity and other metabolic parameters, such as glycemia and lipid profile. The aim of this study was to analy…

Establishing the 99th percentile for high sensitivity cardiac troponin i in healthy blood donors from southern italy

Introduction: The knowledge of high sensitivity cardiac troponin I (hsTnI) distribution in a reference population is mandatory for its introduction in clinical practice. The aim of this study was to define the Upper Reference Limit (URL) of hsTnI measured by Single Molecule Counting technology (SMC) in an accurately selected reference population. Materials and methods: In the study 1140 blood donors were included and selected on the basis of medical history and biomarkers. High sensitivity cardiac troponin I was measured by SMC technology (Clarity, Singulex, Alamed, USA). The 99th percentile was calculated by the non-parametric method according to the Clinical and Laboratory Standard Instit…

The Phenotypic Characterization of the Cammalleri Sisters, an Example of Exceptional Longevity

This article shows demographic, clinical, anamnestic, cognitive, and functional data as well as biochemical, genetic, and epigenetic parameters of two exceptional siblings: Diega (supercentenarian) and Filippa (semisupercentenarian) Cammalleri. The purpose of this study is to provide new insights into the extreme phenotypes represented by semisupercentenarians and supercentenarians. Different studies have been published on supercentenarians, but to the best of our knowledge, this is the only concerning two sisters and the most detailed from a phenotypic point of view. Our findings agree with the suggestion that supercentenarians have an increasing relative resistance to age-related diseases…

Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis

Abstract Objectives Monocyte distribution has recently emerged as a promising biomarker of sepsis, especially in acute setting, such as Emergency Department and Intensive Care Unit. This study aimed to evaluate the accuracy of monocyte distribution width (MDW) for early detecting patients with sepsis by performing a systemic review and meta-analysis of published studies. Methods Relevant publications were identified by a systematic literature search on PubMed and Google Scholar from inception to September 07, 2021. Studies were divided into two groups based on the sepsis criteria applied, namely sepsis-2 or sepsis-3. Results Ten studies including 9,475 individuals, of whom 1,370 with sepsis…

Genotypic and phenotypic aspects of longevity: results from a Sicilian survey and implication for the prevention and the treatment of age-related diseases

Background:It is well known that long living individuals are a model of successful ageing and that the identification of both genetic variants and environmental factors that predispose to a long and healthy life is of tremendous interest for translational medicine.Methods:We present the preliminary findings obtained from an ongoing study on longevity conducted on a sample of Sicilian long-lived individuals.Results:We review the characteristics of longevity in Sicily, taking into account lifestyle, environment, genetics, hematochemical values, body composition and immunophenotype. In addition, we discuss the possible implications of our data for the prevention and/or treatment of age-related…

The role of serum free light chain as biomarker of Myasthenia Gravis

Background and aim: Myasthenia gravis (MG) is a B lymphocyte–mediated disease affecting neuromuscular transmission. The clinical course of MG is unpredictable due to the fluctuating nature and heterogeneity of the disease. Increased levels of free light chains (FLC), which reflect B cell activation, have been detected in different autoimmune disorders. In this study, we evaluated the potential role of FLC as diagnostic and prognostic biomarkers of MG. Materials and methods: 74 MG patients and 52 healthy individuals were included in the study. Serum FLC levels were measured by turbidimetric assay (Freelite, The Binding Site Group Ltd) on the Optilite Analyser System in both groups. In MG pat…

A new tool for sepsis screening in the Emergency Department

Abstract Objectives In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED). Methods Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria. Results Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the pr…

Vitamin D and the nervous system

Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: find…

Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs…

Time-dependent stability of monocyte distribution width (MDW)

Prostate health index (PHI) as a reliable biomarker for prostate cancer: a systematic review and meta-analysis.

Abstract Objectives Prostate cancer (PCa) represents the second most common solid cancer in men worldwide. In the last decades, the prostate health index (PHI) emerged as a reliable biomarker for detecting PCa and differentiating between non-aggressive and aggressive forms. However, before introducing it in clinical practice, more evidence is required. Thus, we performed a systematic review and meta-analysis for assessing the diagnostic performance of PHI for PCa and for detecting clinically significant PCa (csPCa). Methods Relevant publications were identified by a systematic literature search on PubMed and Web of Science from inception to January 11, 2022. Results Sixty studies, including…

Monocyte distribution width (MDW) as a reliable biomarker for urosepsis

Mediterranean nutraceutical foods: Strategy to improve vascular ageing.

Ageing is characterized by a decline in all systemic functions. A greater susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells. They play an important role in neo-angiogenesis and endothelial repair. Vascular ageing is associated with changes in the structure and functions of vessels' wall. There are many possible causes of this damage. For sure, inflammation and oxidative stress play a fundamental role in the pathogenesis of endothelial dysfunction, commonly attributed to a reduced availability of nitric oxide. Inflammageing, the chronic low-grade inflammation that characterizes elderly people, aggravates vascu…

Prognostic Role of CSF β-amyloid 1–42/1–40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1–42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1–40 and Aβ 1–42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a signi…

Validation of glycated albumin reference interval in healthy Caucasian pregnant women

No abstract available

Serum Vitamin D as a Biomarker in Autoimmune, Psychiatric and Neurodegenerative Diseases.

Vitamin D is a steroid hormone regulating calcium-phosphorus homeostasis, immune response and brain function. In the past thirty years, an increasing number of cohort studies, meta-analyses and randomized controlled trials (RTCs) evaluated the serum levels of 25-hydroxyvitamin D [25(OH)D], which is considered the Vitamin D status biomarker, in patients affected by neurological, psychiatric and autoimmune diseases. Although an association between low 25(OH)D serum levels and the prevalence of these diseases has been found, it is still unclear whether the serum 25(OH)D measurement can be clinically useful as a biomarker for diagnosis, prognosis and predicting treatment response in neurodegene…

Clinical Utility of Midregional Proadrenomedullin in Patients with COVID-19

Abstract Objective The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. Methods We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. Results Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3–2.95 vs median, 0.82 nmol/L; interquartile range, 0.57–1.03; …

Longitudinal analysis of anti-SARS-CoV-2 S-RBD IgG antibodies before and after the third dose of the BNT162b2 vaccine.

AbstractImmunosurveillance by evaluating anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the long immunity against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection. The aim of this study was to evaluate the kinetics of antibody response in vaccine recipients. We measured anti-S-RBD IgG levels by indirect chemiluminescence immunoassay on Maglumi 800 (SNIBE, California) in 1013 healthy individuals naïve to SARS-CoV2 infection after two and three COVID-19 vaccine doses. We found that anti-S-RBD IgG levels are higher in females than males. Antibody levels gradually decrease to a steady state after four months since the pea…

Pro-inflammatory status is not a limit for longevity: case report of a Sicilian centenarian

Most studies on centenarians represent them as the best model of ageing. They are defined “delayers”, if they exhibit age-related diseases between 80 and 99 years, “survivors” if they show clinically demonstrable diseases before the age of 80 years, and “escapers” when they attain their 100th year of life without any common age-associated pathologies.

Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer's disease and Parkinson's disease

The current review provides an overview on the development of 25(OH)D measurement standardization tools over the last three decades and clarifies whether there is a role as a serum biomarker for vitamin D in neurological diseases. In the past, a lack of internationally recognized 25(OH)D reference measurement procedures and reference standard materials led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. The vitamin D Standardization Program (VDSP) has been introduced in 2010 to address this problem, however, vitamin D External Quality Assessment Scheme (DEQAS) reports still show substantial sample- to- sample variability. Further, immunoassays, w…

The Role of TAR DNA Binding Protein 43 (TDP-43) as a CandiDate Biomarker of Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis

Background: TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly supports the pathogenetic role of TDP-43 in ALS pathogenesis, the role of TDP-43 as a biomarker of ALS is controversial. We performed a systematic review and meta-analysis to assess the diagnostic performance of TDP-43 for ALS. Methods: Relevant publications were identified by a systematic literature search on PubMed and Web of Science from their inception to 8 April 2022. Results: Seven studies, including 472 individuals, of whom 254 had ALS according to the Revised Amyotrophic Lateral Sclerosis Functional Rating …

Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients.

Summary T helper 9 (Th9) cells and interleukin (IL)-9 are involved in the pathogenesis of several autoimmune diseases. The exact role of IL-9 and Th9 cells in patients with systemic sclerosis (SSc) have not yet been studied adequately. IL-9, IL-9R, transcription factor PU.1 (PU.1), IL-4, thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)-β expression were assessed in skin and kidney biopsies of SSc patients and healthy controls (HC) by immunohistochemistry (IHC). The cellular source of IL-9 was also analysed by confocal microscopy analysis. Peripheral IL-9-producing cells were also studied by flow cytometry. The functional relevance of IL-9 increased expression in SSc …

Association between γ marker, human leucocyte antigens and killer immunoglobulin‐like receptors and the natural course of human cytomegalovirus infection: a pilot study performed in a Sicilian population

Natural killer (NK) cells provide a major defence against cytomegalovirus (HCMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. Also GM allotypes, able to influence the NK antibody-dependent cell-mediated cytotoxicity (ADCC), appear to be involved in the immunological control of virus infections, including HCMV. In some cases, their contribution requires epistatic interaction with other genes of the immune system, such as HLA. In the present report, with the aim to gain insight into the immune mechanisms controlling HCMV, we have studied t…

Comparative analysis of biochip mosaic-based indirect immunofluorescence with enzyme-linked immunosorbent assay for diagnosing myasthenia gravis

Background: The detection of anti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) antibodies is useful in myasthenia gravis (MG) diagnosis and management. BIOCHIP mosaic-based indirect immunofluorescence is a novel analytical method, which employs the simultaneous detection of anti-AChR and anti-MuSK antibodies in a single miniature incubation field. In this study, we compare, for the first time, the BIOCHIP MG mosaic with conventional enzyme-linked immunosorbent assay (ELISA) in the diagnosis of MG. Methods: A total of 71 patients with MG diagnosis were included in the study. Anti-AChR and anti-MuSK antibodies were measured separately by two different ELISA an…

Monocyte distribution width as a biomarker of sepsis in the intensive care unit: A pilot study.

Background Monocyte distribution width has been recently proposed as a sepsis biomarker in the emergency department. The aim of this study was to assess the role of monocyte distribution width as a diagnostic biomarker of sepsis in the intensive care unit. Methods In this prospective observational study, we included all consecutive patients admitted to the intensive care unit of the University Hospital “P. Giaccone” of Palermo. Patients were classified into three groups according to Sepsis-3 criteria: (1) patients without sepsis; (2) patients developing sepsis during their hospital stay; (3) patients admitted with sepsis. Monocyte distribution width was measured at admission (groups 1, 2, 3…

The Value of a Complete Blood Count (CBC) for Sepsis Diagnosis and Prognosis.

Sepsis represents an important global health burden due to its high mortality and morbidity. The rapid detection of sepsis is crucial in order to prevent adverse outcomes and reduce mortality. However, the diagnosis of sepsis is still challenging and many efforts have been made to identify reliable biomarkers. Unfortunately, many investigated biomarkers have several limitations that do not support their introduction in clinical practice, such as moderate diagnostic and prognostic accuracy, long turn-around time, and high-costs. Complete blood count represents instead a precious test that provides a wealth of information on individual health status. It can guide clinicians to early-identify …

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus.

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detecti…

Uncoupling Protein 2 as genetic risk factor for systemic lupus erythematosus: association with malondialdehyde levels and intima media thickness

BACKGROUND Increased oxidative stress potentially leads to accelerated atherosclerosis and, consequently, cardiovascular diseases, the main cause of death in systemic lupus erythematous (SLE). To gain insight into these mechanisms, we studied the association of uncoupling protein (UCP) 2 genetic variants, gene involved in the mitochondrial production of reactive oxygen species, and oxidative stress with SLE and the presence of atherosclerosis. METHODS Genetic analysis of the UCP2 -866G/A and UCP2 Ins/Del polymorphisms was performed in 45 SLE patients and 36 healthy controls by RFLP-PCR. Oxidation status was determined by measuring malondialdehyde (MDA) levels. Presence of subclinical athero…

Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention

Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naive cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the rol…

Vitamin D in malaria: more hypotheses than clues

Abstract Vitamin D is a secosteroid hormone regulating calcium and phosphate metabolism, immune response and brain development. Low blood 25(OH)D levels have been reported in patients affected by infectious diseases caused by parasites, including malaria. Despite the high effectiveness of antimalarials, malaria is burdened with high morbidity and mortality, and the search for additional therapies is rapidly growing. Furthermore, available preventive measures have proved to be barely effective so far. Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesized some mechanisms by which the hormone can influence malaria pathogenesis, a…

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn…

Monocyte Distribution Width (MDW) as a biomarker of sepsis: An evidenced-based laboratory medicine approach.

Monocyte Distribution Width (MDW) is a new generation cell blood count parameter providing a measure of monocyte anisocytosis. In the last decades, it has emerged as a reliable biomarker of sepsis in the acute setting, especially emergency department, and intensive care unit. MDW has several advantages over commonly used sepsis biomarkers, including low-cost, ease and speed of measurement. The clinical usefulness of MDW has been established in several studies and some clinical laboratory medicines have already implemented it in their routine. In this article, we describe the analytical and clinical features of MDW to guide its appropriate use in clinical practice by integrating the research…

The Role of Vitamin D as a Biomarker in Alzheimer’s Disease

Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on the…

Effect of Extra Virgin Olive Oil and Table Olives on the ImmuneInflammatory Responses: Potential Clinical Applications

Background and Objective: Extra virgin olive oil (EVOO) is the common element among the Mediterranean countries. It can be considered a nutraceutical and functional food, thanks to its bioactive compounds. It can act and modulate different processes linked to ageing and age-related diseases related to a common chronic low grade inflammation. Depending on the cultivar, the growth conditions, the period of harvesting, the productive process and time of product storage, EVOO could contain different amount of vegetal components. Of course, the same is for table olives. Methods: The aim of our review is to summarize the effects of EVOO and table olives on the immunemediated inflammatory respons…

Validation of monocyte distribution width decisional cutoff for sepsis detection in the acute setting

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Reference interval of monocyte distribution width (MDW) in healthy blood donors.

Abstract Background The aim of the study was to accurately establish the reference interval (RI) of monocyte distribution width (MDW) in healthy blood donors by the direct method using different statistical approaches. Methods MDW was measured in 486 subjects. RI of MDW was calculated by the non-parametric method, the robust method and, the Harrell-Davis bootstrap method and using different tests to identify potential outliers (Dixon-Reed and Tukey). Results Lower and upper reference limits of the RI calculated by the non-parametric method were, 16.22 (90%CI 15.78–16.47) – 23.15 (90%CI 22.80–24.10) (without outlier removal), and 16.44 (90%CI 16.21–16.67) – 22.99 (90%CI 22.33–23.22) (after o…

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer’s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological …

Association of immunoglobulin GM allotypes with longevity in long-living individuals from Southern Italy

Abstract Background The aim of this study was to analyse the role of GM allotypes, i.e. the hereditary antigenic determinants expressed on immunoglobulin polypeptide chains, in the attainment of longevity. The role played by immunoglobulin allotypes in the control of immune responses is well known as well as the role of an efficient immune response in longevity achievement. So, it is conceivable that particular GM allotypes may contribute to the generation of an efficient immune response that supports successful ageing, hence longevity. Methods In order to show if GM allotypes play a role in the achievement of longevity, we typed the DNA of 95 Long-living individuals (LLIs) and 96 young con…

Preliminary reference intervals of Glycated Albumin in healthy Caucasian pregnant women

Abstract Background and aims Glycated albumin (GA) could represent a useful biomarker in pregnant women for diagnosing and monitoring gestational diabetes mellitus (GDM). The establishment of reference intervals (RI) is mandatory before assessing its clinical usefulness. The RIs of GA in healthy pregnant women are not well defined. The aim of the current study was to establish the RI in a cohort consisting of Caucasian pregnant women without overt diabetes mellitus or gestational diabetes mellitus. Methods The study included 183 healthy pregnant women. GA was measured on plasma by an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The RI was calculated by the non-parametr…

The KIR-ligand HLA-A Bw4 predicts the outcome of hepatitis B infection.

Killer Immunoglobulin like Receptors (KIR) are membrane proteins expressed on Natural Killer (NK) cells and on a small subset of CD8 lymphocytes. They influence the activation or inhibition of both cell types through interaction with their ligands, represented by Human Leukocyte Antigen (HLA) class I molecules. Several studies have shown that KIR/HLA interactions are involved in the pathogenesis and progression of different diseases as viral infections, autoimmune-disorders, or cancer, conditioning susceptibly to or protection against the outcome of the disease. HBV infection represents a major health problem with 2 billion people infected and 3 hundred and fifty million people with chronic…

Evaluation of Anti-SARS-Cov-2 S-RBD IgG Antibodies after COVID-19 mRNA BNT162b2 Vaccine

(1) Background: The evaluation of anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the individual protection against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection

Aging and neuroinflammatory disorders: New biomarkers and therapeutic targets

: Chronic neuroinflammation is a common feature of the pathogenic mechanisms involved in various neurodegenerative age-associated disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson’s disease, and dementia. : In particular, persistent low-grade inflammation may disrupt the brain endothelial barrier and cause a significant increase of pro-inflammatory cytokines and immune cells into the cerebral tissue that, in turn, leads to microglia dysfunction and loss of neuroprotective properties. : Nowadays, growing evidence highlights a strong association between persistent peripheral inflammation, as well as metabolic alterations, and neurodegenerative disorder susceptibility. The…

Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity.

INTRODUCTION: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS. METHODS: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were mea…

Nutraceutical effects of table green olives: a pilot study with Nocellara del Belice olives

Background: The aim of this study was to analyse the nutraceutical properties of table green olives Nocellara del Belice, a traditional Mediterranean food. The Mediterranean Diet has as key elements olives and extra virgin olive oil, common to all Mediterranean countries. Olive oil is the main source of fat and can modulate oxidative stress and inflammation, whereas little is known about the role of olives. Moreover, emerging evidences underline the association between gut microbiota and food as the basis of many phenomena that affect health and delay or avoid the onset of some age-related chronic diseases. Methods: In order to show if table green olives have nutraceutical properties and/or…

Evaluation of Alpha-Synuclein Cerebrospinal Fluid Levels in Several Neurological Disorders

(1) Background: Alpha-synuclein (α-syn) is a presynaptic neuronal protein that regulates several neuronal functions. In recent decades, the role of α-syn as a biomarker of neurodegenerative diseases has been explored, especially in synucleinopathies. However, only a few studies have assessed its role as biomarker in other neurological disorders. The aim of the study was to evaluate cerebrospinal fluid (CSF) α-syn levels in several neurological disorders; (2) Methods: We measured CSF α-syn levels by a commercial ELISA kit in 158 patients classified in the following group: controls, Alzheimer’s Disease (AD), cerebrovascular diseases, inflammatory central nervous …

Sicilian centenarian offspring are more resistant to immune ageing

Background: Immunosenescence constitutes a major indirect cause of morbidity and mortality in the elderly. Previous analysis of immune signatures in a cohort of centenarian offspring showed an intermediate immunophenotype between age-matched and younger controls. Aims: To confirm and extend the previous studies performing further phenotypical analysis in centenarian offspring and controls. Methods: Analysis of Treg cells, γδ T cells, mucosal-associated invariant T cells, and senescent immune T cells was performed in centenarian offspring and controls. Results: We report significant differences between elderly and centenarian offspring in most of the studied subsets, showing that centenarian…

Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis

BACKGROUND AND PURPOSE To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls. METHODS We enrolled 196 ALS patients and 91 controls, who included patients with ALS-mimicking diseases and those with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay. R…

Neurogranin as a Novel Biomarker in Alzheimer's Disease

Abstract Background In this study, we investigated the possible role of 2 novel biomarkers of synaptic damage, namely, neurogranin and α-synuclein, in Alzheimer disease (AD). Methods The study was performed in a cohort consisting of patients with AD and those without AD, including individuals with other neurological diseases. Cerebrospinal fluid (CSF) neurogranin and α-synuclein levels were measured by sensitive enzyme-linked immunosorbent assays (ELISAs). Results We found significantly increased levels of CSF neurogranin and α-synuclein in patients with AD than those without AD. Neurogranin was correlated with total tau (tTau) and phosphorylated tau (pTau), as well as with cognitive declin…

Molecular approaches in autoimmunity and ageing: potential implications for future therapies.

My researches during my PhD were mainly focused on two aspects. The first one, was to study molecular aspects potentially implicated in autoimmunity pathogenesis, in order to identify new potential risk factors useful as therapeutic target. To this end, we focused on two severe and wasting systemic autoimmune diseases: systemic lupus erythematosus and systemic sclerosis. Pathogenesis of these diseases has still not clear and early diagnosis is difficult to identify because of complex and heterogeneous presentation of symptoms. A strong genetic association between HLA and disease susceptibility is well accept, nevertheless, other factors as oxidative stress, KIR and inflammatory cytokines ha…

Comparison of a rapid immunochromatographic test with a chemiluminescence immunoassay for detection of anti-SARS-CoV-2 IgM and IgG

Introduction: The 2019 Coronavirus disease (COVID-19) has been characterized as a pandemic, representing a serious global public health emergency. Serological tests have been proposed as reliable tools for detecting Coronavirus SARS-CoV-2 antibodies in infected patients, especially for surveillance or epidemiological purposes. The aim of this study is to evaluate the agreement between the IgM/IgG rapid assays, based on lateral flow immunochromatographic assay, and the fully automated 2019-nCoV IgM and IgG, based on chemiluminescence immunoassay. Materials and methods: SARS-CoV-2 antibodies were measured with the BIOSYNEX COVID-19 BSS IgM/IgG test (BIOSYNEX, Illkirch-Graffenstaden, France) a…

Translation of Basic Research into Clinics: Killer Immunoglobulin-like Receptors Genes in Autoimmune and Infectious Diseases

Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIRs and HLA loci are highly polymorphic, and some of their combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIRs profiles may be detrimental in autoimmune pathogenesis, and specific KIRs may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. So, considering that in the pathogenesis of many autoimmune disorders and infections innate immunity plays a key role, the recent …

Nutrient sensing pathways as therapeutic targets for healthy ageing

Introduction: In the present paper, the authors have discussed anti-aging strategies which aim to slow the aging process and to delay the onset of age-related diseases, focusing on nutrient sensing pathways (NSPs) as therapeutic targets. Indeed, several studies have already demonstrated that both in animal models and humans, dietary interventions might have a positive impact on the aging process through the modulation of these pathways. Areas covered: Achieving healthy aging is the main challenge of the twenty-first century because lifespan is increasing, but not in tandem with good health. The authors have illustrated different approaches that can act on NSPs, modulating the rate of the ag…

Role of Immunogenetics in the Outcome of HCMV Infection: Implications for Ageing

The outcome of host-virus interactions is determined by a number of factors, some related to the virus, others to the host, such as environmental factors and genetic factors. Therefore, different individuals vary in their relative susceptibility to infections. Human cytomegalovirus (HCMV) is an important pathogen from a clinical point of view, as it causes significant morbidity and mortality in immunosuppressed or immunosenescent individuals, such as the transplanted patients and the elderly, respectively. It is, therefore, important to understand the mechanisms of virus infection control. In this review, we discuss recent advances in the immunobiology of HCMV-host interactions, with partic…