198 results on '"Roberto Paganelli"'
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2. Temporal trends, sex differences, and age-related disease influence in Neutrophil, Lymphocyte count and Neutrophil to Lymphocyte-ratio: results from InCHIANTI follow-up study
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Raffaello Pellegrino, Roberto Paganelli, Angelo Di Iorio, Stefania Bandinelli, Antimo Moretti, Giovanni Iolascon, Eleonora Sparvieri, Domiziano Tarantino, and Luigi Ferrucci
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Neutrophils ,Lymphocytes ,Neutrophils-to-Lymphocytes-ratio ,Observational study ,Longitudinal study ,Temporal-trends ,Immunologic diseases. Allergy ,RC581-607 ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background Neutrophils and lymphocytes represent the larger percentage of all white blood cells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of several clinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years’ follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population. Methods The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session. Results The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value = 0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants. Conclusion NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases.
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- 2023
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3. Natural IgG antibodies to β amyloid are decreased in patients with Parkinson’s disease
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Roberto Paganelli, Alessia Paganelli, Graham Pawelec, and Angelo Di Iorio
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Parkinson's disease ,Alzheimer's dementia ,Anti-amyloid β ,Antibodies ,Neurodegeneration ,Neuroimmunology ,Immunologic diseases. Allergy ,RC581-607 ,Geriatrics ,RC952-954.6 - Abstract
Abstract Natural antibodies (nAbs) against aggregation-prone proteins have been found in healthy normal subjects. These proteins likely have a pathogenetic role in neurodegenerative diseases of ageing. They include the amyloid β (Aβ) protein which may play an important role in Alzheimer’s dementia (AD), and α-synuclein, a major determinant of Parkinson’s disease (PD). We measured nAbs to Aβ in a group of Italian patients with AD, vascular dementia, non-demented PD patients and healthy elderly controls. We found that Aβ antibody levels in AD were similar to age- and sex-matched controls, but contrary to our expectations, they were significantly reduced in PD. This may identify patients that could be more prone to amyloid aggregation.
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- 2023
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4. When Cell-Mediated Immunity after Vaccination Is Important
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Roberto Paganelli
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n/a ,Medicine - Abstract
The review by Reeg D [...]
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- 2024
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5. Editorial: Case reports in respiratory pharmacology 2022
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Przemyslaw Zdziarski, Luisa Ricciardi, and Roberto Paganelli
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respiratory pharmacology ,case study ,patient-centered care ,SARS-CoV-2 ,corticosteroids ,pharmacovigilance ,Therapeutics. Pharmacology ,RM1-950 - Published
- 2023
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6. Aging and Immunity in COVID-19
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Roberto Paganelli
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aging ,sars ,covid-19 ,comorbidity ,immunity ,immunosenescence ,Medicine - Abstract
The COVID-18 pandemic severely affected people older than 65 years, especially those with age-related comorbidities, causing a disproportionate death burden in this age group. The reasons for this difference from other respiratory virus pandemics have been attributed to the aging-induced changes in the immune system, and their effects on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. In this brief review, I summarize some of the recent findings throwing light on the relationship between aging, immunity, and the severity of COVID-19.
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- 2022
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7. Platelet-Rich Plasma (PRP) and Adipose-Derived Stem Cell (ADSC) Therapy in the Treatment of Genital Lichen Sclerosus: A Comprehensive Review
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Alessia Paganelli, Luca Contu, Alessandra Condorelli, Elena Ficarelli, Alfonso Motolese, Roberto Paganelli, and Alberico Motolese
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lichen sclerosus ,PRP ,ADSC ,mesenchymal stromal cells ,regenerative medicine ,vulvar atrophy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Lichen sclerosus (LS) is a chronic inflammatory dermatosis mostly localized in the genital area, characterized by vulvar alterations that can severely impact a patient’s quality of life. Current treatment modalities often provide incomplete relief, and there is a need for innovative approaches to manage this condition effectively. Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) have emerged as potential regenerative therapies for LS, offering promising results in clinical practice. This comprehensive review explores the utilization of PRP and ADSC therapy in the treatment of genital LS, highlighting their mechanisms of action, safety profiles, and clinical outcomes. PRP is a blood product enriched in growth factors and cytokines, which promotes tissue regeneration, angiogenesis, and immune modulation. ADSC regenerative potential relies not only in their plasticity but also in the secretion of trophic factors, and modulation of the local immune response. Numerous studies have reported the safety of PRP and ADSC therapy for genital LS. Adverse events are minimal and typically involve mild, self-limiting symptoms, such as transient pain and swelling at the injection site. Long-term safety data are encouraging, with no significant concerns identified in the literature. PRP and ADSC therapy have demonstrated significant improvements in LS-related symptoms, including itching, burning, dyspareunia, and sexual function. Additionally, these therapies enable many patients to discontinue the routine use of topical corticosteroids. Several studies have explored the efficacy of combining PRP and ADSC therapy for LS. In combination, PRP and ADSCs seem to offer a synergistic approach to address the complex pathophysiology of LS, particularly in the early stages. The use of PRP and ADSC therapy for genital lichen sclerosus represents a promising and safe treatment modality. These regenerative approaches have shown significant improvements in LS-related symptoms, tissue trophism, and histological features. Combination therapy, which harnesses the synergistic effects of PRP and ADSCs, is emerging as a preferred option, especially in early-stage LS cases. Further research, including randomized controlled trials and long-term follow-up, is warranted to elucidate the full potential and mechanisms of PRP and ADSC therapy in the management of genital LS. These regenerative approaches hold great promise in enhancing the quality of life of individuals suffering from this challenging condition.
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- 2023
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8. A Tribute to Two Master Teachers of Immunology
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Roberto Paganelli
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n/a ,Biology (General) ,QH301-705.5 - Abstract
A Special Issue dedicated in memory of Prof. Fernando Aiuti is a special tribute to a clinician who led the field of Clinical Immunology in Italy and introduced the entire Italian medical and academic scene to it. [...]
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- 2023
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9. Insights from a Case of Good’s Syndrome (Immunodeficiency with Thymoma)
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Roberto Paganelli, Michela Di Lizia, Marika D’Urbano, Alessia Gatta, Alessia Paganelli, Paolo Amerio, and Paola Parronchi
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Good’s syndrome ,thymoma ,hypogammaglobulinemia ,cellular immunity ,immunophenotype ,autoantibodies ,Biology (General) ,QH301-705.5 - Abstract
Immunodeficiency with thymoma was described by R.A. Good in 1954 and is also named after him. The syndrome is characterized by hypogammaglobulinemia associated with thymoma and recurrent infections, bacterial but also viral, fungal and parasitic. Autoimmune diseases, mainly pure red cell aplasia, other hematological disorders and erosive lichen planus are a common finding. We describe here a typical case exhibiting all these clinical features and report a detailed immunophenotypic assessment, as well as the positivity for autoantibodies against three cytokines (IFN-alpha, IL-6 and GM-CSF), which may add to known immune abnormalities. A review of the published literature, based on case series and immunological studies, offers some hints on the still unsolved issues of this rare condition.
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- 2023
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10. Inhibition of LPS-Induced Inflammatory Response of Oral Mesenchymal Stem Cells in the Presence of Galectin-3
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Alessia Paganelli, Francesca Diomede, Guya Diletta Marconi, Jacopo Pizzicannella, Thangavelu Soundara Rajan, Oriana Trubiani, and Roberto Paganelli
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GAL-3 ,galectin ,inflammation ,LPS ,mesenchymal stem cell ,TLR ,Biology (General) ,QH301-705.5 - Abstract
Galectin-3 (GAL-3) is a beta-galactoside binding lectin produced by mesenchymal stem cells (MSCs) and other cell sources under inflammatory conditions. Several studies have reported that GAL-3 exerts an anti-inflammatory action, regulated by its natural ligand GAL-3 BP. In the present study, we aimed to assess the GAL-3 mediated regulation of the MSC function in an LPS-induced inflammation setting. Human gingival mesenchymal stem cells (hGMSCs) were stimulated in vitro with LPSs; the expression of TLR4, NFκB p65, MyD88 and NALP3 were assessed in the hGMSCs via immunofluorescence imaging using confocal microscopy, Western blot assay, and RT-PCR before and after the addition of GAL-3, both alone and with the addition of its inhibitors. LPSs stimulated the expression of TLR4, NFκB p65, MyD88 and NALP3 in hGMSCs, which was inhibited by GAL-3. The addition of either GAL3-BP or the antibody to GAL-3 were able to revert the GAL-3-mediated effects, restoring the expression of TLR4, NFκB p65, MyD88 and NALP3. GAL-3 induces the downregulation of the LPS-induced inflammatory program in MSCs.
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- 2023
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11. Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study
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Zeinab A. El-Sayed, MD, PhD, Dalia H. El-Ghoneimy, MD, PhD, José A. Ortega-Martell, MD, Nesrine Radwan, MD, PhD, Juan C. Aldave, MD, Waleed Al-Herz, MD, Maryam A. Al-Nesf, MD, ABHS, Antonio Condino-Neto, MD, PhD, Theresa Cole, MD, PhD, Brian Eley, MD, Nahla H.H. Erwa, DipRCPATH, Sara Espinosa-Padilla, PhD, Emilia Faria, MD, Nelson A. Rosario Filho, MD, PhD, Ramsay Fuleihan, MD, Nermeen Galal, MD, PhD, Elizabeth Garabedian, RN, MSLS, Mary Hintermeyer, BN, Kohsuke Imai, MD, PhD, Carla Irani, MD, MSCE, Ebtihal Kamal, MD, Nadia Kechout, MD, PhD, Adam Klocperk, MD, PhD, Michael Levin, MD, PhD, Tomas Milota, MD, PhD, Monia Ouederni, MD, Roberto Paganelli, MD, Claudio Pignata, MD, PhD, Farah N. Qamar, MBBS, FCPS, MSc, DHPE, FRCP, Isabella Quinti, MD, PhD, Sonia Qureshi, MBBS, FCPS, MSc, Nita Radhakrishnan, MD, PhD, Nima Rezaei, MD, PhD, John Routes, MD, PhD, Surjit Singh, MD, DCH (Lon.), FRCP (Lon.), FRCPCH (Lon.), FAMS, Sangeetha Siniah, MBBS, MRCPCH, Intisar Abdel-Hakam Taha, MD, SMSB, Luciana K. Tanno, MD, Ph.D, Ben Van Dort, BN, Alla Volokha, MD, PhD, DSc, and Kathleen Sullivan, MD, PhD
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Primary immunodeficiency ,Asthma ,Atopic dermatitis ,IVIG ,Omalizumab ,Anaphylaxis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. Results: Thirty centers in 23 countries caring for a total of 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10–28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3–11.3%) had bronchial asthma, 3.6% (1.9–9.1%) atopic dermatitis, 3.0% (1.0–7.8%) allergic rhinitis, and 1.3% (0.5–3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5–25%) and diagnosis delay was reported in 7.5% (0.9–20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2–62.5%) and 20.0% (10–32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.
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- 2022
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12. Multiplex Proteomic Evaluation in Inborn Errors with Deregulated IgE Response
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Enrico Scala, Stefania Madonna, Daniele Castiglia, Alessandro Scala, Elisabetta Caprini, and Roberto Paganelli
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inborn error ,Comel–Netherton syndrome ,recessive X–linked ichthyosis ,Hyper–IgE ,TSPAN7 ,MID1IP1 ,Biology (General) ,QH301-705.5 - Abstract
(1) Background: Atopic dermatitis constitutes one of the most common inflammatory skin manifestations of the pediatric population. The onset of many inborn errors occurs early in life with an AD–like picture associated with a deregulated IgE response. The availability of proteomic tests for the simultaneous evaluation of hundreds of molecules allows for more precise diagnosis in these cases. (2) Methods: Comparative genomic hybridization microarray (Array–CGH) analysis and specific IgE evaluation by using allergenic microarray (ISAC) and microarray (ALEX2) systems were performed. (3) Results: Proteomic investigations that use multiplex methods have proven to be extremely useful to diagnose the sensitization profile in inborn errors with deregulated IgE synthesis. Four patients with rare diseases, such as recessive X–linked ichthyosis (RXLI, OMIM 308100), Comel–Netherton syndrome (NS, OMIM256500), monosomy 1p36 syndrome (OMIM: 607872), and a microduplication of Xp11.4 associated with extremely high levels of IgE: 7.710 kU/L, 5.300 kU/L, 1.826 kU/L, and 10.430 kU/L, respectively, were evaluated by micro– and macroarray multiplex methods. Polyreactivity to both environmental and food allergens was observed in all cases, including the first described case of association of X–chromosome microduplication and HIE. (4) Conclusions: Extensive use of proteomic diagnostics should be included among the procedures to be implemented in inborn errors with hyper–IgE.
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- 2023
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13. Vernal Keratoconjunctivitis: A Case of Anti-IgE Treatment with Short-Lasting Remission
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Alessia Gatta, Loredana Della Valle, Anila Farinelli, Gilda Scarano, Arianna Lumaca, Enrico Cavallucci, Mario Di Gioacchino, and Roberto Paganelli
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omalizumab ,ige ,corneal ulcer ,giant papillae ,Ophthalmology ,RE1-994 - Abstract
Vernal keratoconjunctivitis (VKC) is a persistent, severe allergic eye disease, mainly occurring in children, that can lead to severe ocular complications including visual loss. The underlying etiology and pathophysiology of VKC remain unclear. Common therapies include topical antihistamines and mast cell stabilizers that are effective in mild-to-moderate forms of VKC but are often ineffective in severe forms that require topical or systemic corticosteroids. Dependence on steroids is common with potential adverse effects both local, as increased intraocular pressure, glaucoma, infection and cataract, as well as systemic ones, as reduction in child growth velocity. Alternative therapies are immunosuppressive drugs, like cyclosporine A and tacrolimus, that usually are effective but may also cause adverse effects. A promising therapeutic option is omalizumab, a recombinant anti-IgE humanized monoclonal antibody, currently used as add-on therapy for moderate to severe uncontrolled allergic asthma and chronic spontaneous urticaria. Here, we report the short-time duration of effective relief of symptoms after the prolonged use of omalizumab in a patient affected by refractory VKC. However, in our case any apparent beneficial effect was short lasting, and we propose that the duration of the disease and the concomitant long-term use of steroids leads to iatrogenic damage; thus, the disease becomes refractory to anti-IgE treatment.
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- 2020
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14. Urinary and Daily Assumption of Polyphenols and Hip-Fracture Risk: Results from the InCHIANTI Study
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Raffaello Pellegrino, Roberto Paganelli, Stefania Bandinelli, Antonio Cherubini, Cristina Andrés-Lacueva, Angelo Di Iorio, Eleonora Sparvieri, Raul Zamora-Ros, and Luigi Ferrucci
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bone-pQCT ,dietary polyphenols ,longitudinal study ,urinary polyphenols ,femur fracture risk ,Nutrition. Foods and food supply ,TX341-641 - Abstract
A high polyphenol intake has been associated with higher bone-mineral density. In contrast, we recently demonstrated that the urinary levels of these micronutrients were associated with the long-term accelerated deterioration of the bone. To expand on the health consequences of these findings, we assessed the association between urinary level and dietary intake of polyphenols and the 9-year risk of hip fractures in the InCHIANTI study cohort. The InCHIANTI study enrolled representative samples from two towns in Tuscany, Italy. Baseline data were collected in 1998 and at follow-up visits in 2001, 2004, and 2007. Of the 1453 participants enrolled at baseline, we included 817 participants in this study who were 65 years or older at baseline, donated a 24 hour urine sample, and underwent a quantitative computerized tomography (pQCT) of the tibia. Fracture events were ascertained by self-report over 9 years of follow-up. Thirty-six hip fractures were reported over the 9-year follow-up. The participants who developed a hip fracture were slightly older, more frequently women, had a higher dietary intake of polyphenols, had higher 24-hour urinary polyphenols excretion, and had a lower fat area, muscle density, and cortical volumetric Bone Mineral Density (vBMD) in the pQCT of the tibia. In logistic regression analyses, the baseline urinary excretion of total polyphenols, expressed in mg as a gallic acid equivalent, was associated with a higher risk of developing a hip fracture. Dietary intake of polyphenols was not associated with a differential risk of fracture. In light of our findings, the recommendation of an increase in dietary polyphenols for osteoporosis prevention should be considered with caution.
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- 2022
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15. Resurrecting Epstein–Barr Virus
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Roberto Paganelli
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n/a ,Medicine - Abstract
One of the Editor’s choice articles in 2021 published in Pathogens was an early assessment of the role of Epstein–Barr virus (EBV) reactivation in the pathogenesis of long-term symptoms associated with COVID-19 [...]
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- 2022
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16. Omalizumab in chronic spontaneous urticaria: steroid sparing effect
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Alessia Gatta, Loredana Della Valle, Anila Farinelli, Enrico Cavallucci, Roberto Paganelli, and Mario Di Gioacchino
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chronic spontaneous urticaria ,steroid-dependent urticaria ,autologous serum and plasma skin test ,omalizumab ,Dermatology ,RL1-803 - Abstract
Omalizumab has been recognized to be effective in the treatment of chronic spontaneous urticaria (CSU). The Italian Medicines Agency authorizes two omalizumab courses, only for patients with CSU unresponsive to antihistamines, and this schedule may limit omalizumab use. Unfortunately, in the majority of CSU, the schedule is unsatisfactory because symptoms usually recur shortly after discontinuation of treatment. A case of a patient needing more than two treatment courses with omalizumab is reported, in order to discuss the rationale for its long-term use. Patient had needed systemic steroids almost continuously for 4 years. Two severe glucocorticoid-associated adverse events (GAEs) occurred during long-term treatment. Omalizumab 300 mg monthly was started with immediate disappearance of the urticarial lesions. Beneficial effects waned shortly after discontinuation of treatment, and further steroid use was needed. A second omalizumab course showed the same clinical pattern, with prompt response and recurrence of symptoms after suspension. Therefore, we decided to repeat the 6 months omalizumab treatment as soon as symptoms recurred, to avoid further emergency steroid treatments and GAEs. This experience suggests that long-term use of omalizumab could be useful. Evidences show that omalizumab is effective and safe for re-treatment and long-term use of responding patients after recurrence.
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- 2018
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17. Immunomodulating Profile of Dental Mesenchymal Stromal Cells: A Comprehensive Overview
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Alessia Paganelli, Oriana Trubiani, Francesca Diomede, Alessandra Pisciotta, and Roberto Paganelli
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T cells ,immunomodulation ,dental ,cytokines ,extracellular vesicles ,mesenchymal stem cells (MeSH ID D059630) ,Dentistry ,RK1-715 - Abstract
Dental mesenchymal stromal cells (MSCs) are multipotent cells present in dental tissues, characterized by plastic adherence in culture and specific surface markers (CD105, CD73, CD90, STRO-1, CD106, and CD146), common to all other MSC subtypes. Dental pulp, periodontal ligament, apical papilla, human exfoliated deciduous teeth, alveolar bone, dental follicle, tooth germ, and gingiva are all different sources for isolation and expansion of MSCs. Dental MSCs have regenerative and immunomodulatory properties; they are scarcely immunogenic but actively modulate T cell reactivity. in vitro studies and animal models of autoimmune diseases have provided evidence for the suppressive effects of dental MSCs on peripheral blood mononuclear cell proliferation, clearance of apoptotic cells, and promotion of a shift in the Treg/Th17 cell ratio. Appropriately stimulated MSCs produce anti-inflammatory mediators, such as transforming growth factor-β (TGF-β), prostaglandin E2, and interleukin (IL)-10. A particular mechanism through which MSCs exert their immunomodulatory action is via the production of extracellular vesicles containing such anti-inflammatory mediators. Recent studies demonstrated MSC-mediated inhibitory effects both on monocytes and activated macrophages, promoting their polarization to an anti-inflammatory M2-phenotype. A growing number of trials focusing on MSCs to treat autoimmune and inflammatory conditions are ongoing, but very few use dental tissue as a cellular source. Recent results suggest that dental MSCs are a promising therapeutic tool for immune-mediated disorders. However, the exact mechanisms responsible for dental MSC-mediated immunosuppression remain to be clarified, and impairment of dental MSCs immunosuppressive function in inflammatory conditions and aging must be assessed before considering autologous MSCs or their secreted vesicles for therapeutic purposes.
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- 2021
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18. Biological clocks: their relevance to immune-allergic diseases
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Roberto Paganelli, Claudia Petrarca, and Mario Di Gioacchino
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Circadian rhythm ,Biological clock ,Immune system ,Allergy ,Chronopharmacology ,Shift work ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made in the past 15 years on the genetic and molecular mechanisms regulating many physiological functions, has renewed the attention to the importance of circadian rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus in the brain, photoentrained via direct connection with melanopsin containing, intrinsically light-sensitive retinal ganglion cells, and it projects to periphery, thus creating an inner circadian rhythm. This regulates several activities, including sleep, feeding times, energy metabolism, endocrine and immune functions. Disturbances of these rhythms, mainly of wake/sleep, hormonal secretion and feeding, cause decrease in quality of life, as well as being involved in development of obesity, metabolic syndrome and neuropsychiatric disorders. Most immunological functions, from leukocyte numbers, activity and cytokine secretion undergo circadian variations, which might affect susceptibility to infections. The intensity of symptoms and disease severity show a 24 h pattern in many immunological and allergic diseases, including rheumatoid arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is accompanied by altered sleep duration and quality, a major determinant of quality of life. Shift work and travel through time zones as well as artificial light pose new health threats by disrupting the circadian rhythms. Finally, the field of chronopharmacology uses these concepts for delivering drugs in synchrony with biological rhythms.
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- 2018
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19. Improvement of Inflammation and Pain after Three Months’ Exclusion Diet in Rheumatoid Arthritis Patients
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Maria Teresa Guagnano, Chiara D’Angelo, Daniela Caniglia, Pamela Di Giovanni, Eleonora Celletti, Emanuela Sabatini, Lorenza Speranza, Marco Bucci, Francesco Cipollone, and Roberto Paganelli
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rheumatoid arthritis ,inflammation ,pain ,dietary regimen ,meat- gluten- and lactose-exclusion diet ,bioimpedance analysis ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. Methods: In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months’ dietary regimens. Results: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. Conclusions: Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.
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- 2021
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20. X-linked agammaglobulinemia (XLA): Phenotype, diagnosis, and therapeutic challenges around the world
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Zeinab A. El-Sayed, Irina Abramova, Juan Carlos Aldave, Waleed Al-Herz, Liliana Bezrodnik, Rachida Boukari, Ahmed Aziz Bousfiha, Caterina Cancrini, Antonio Condino-Neto, Ghassan Dbaibo, Beata Derfalvi, Figen Dogu, J.David M. Edgar, Brian Eley, Rasha Hasan El-Owaidy, Sara Elva Espinosa-Padilla, Nermeen Galal, Filomeen Haerynck, Rima Hanna-Wakim, Elham Hossny, Aydan Ikinciogullari, Ebtihal Kamal, Hirokazu Kanegane, Nadia Kechout, Yu Lung Lau, Tomohiro Morio, Viviana Moschese, Joao Farela Neves, Monia Ouederni, Roberto Paganelli, Kenneth Paris, Claudio Pignata, Alessandro Plebani, Farah Naz Qamar, Sonia Qureshi, Nita Radhakrishnan, Nima Rezaei, Nelson Rosario, John Routes, Berta Sanchez, Anna Sediva, Mikko RJ. Seppanen, Edith Gonzalez Serrano, Anna Shcherbina, Surjit Singh, Sangeetha Siniah, Guiseppe Spadaro, Mimi Tang, Ana Maria Vinet, Alla Volokha, and Kathleen E. Sullivan
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features. Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries. Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians. Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications. Keywords: XLA, Agammaglobulinemia, Infection, Autoimmunity, Outcomes, Immunoglobulin, Therapy
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- 2019
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21. Aging, Obesity, and Inflammatory Age-Related Diseases
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Daniela Frasca, Bonnie B. Blomberg, and Roberto Paganelli
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aging ,obesity ,inflammation ,type-2 diabetes ,rheumatoid arthritis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The increase in the prevalence of obesity represents a worldwide phenomenon in all age groups and is pathologically and genetically correlated with several metabolic and cardiovascular diseases, representing the most frequent age-related diseases. Obesity superimposed on aging drastically increases chronic low-grade inflammation (inflammaging), which is an important link between obesity, insulin resistance, and age-associated diseases. Immune cells of both the innate and the adaptive immune systems infiltrate the adipose tissue (AT) and during obesity induce inflammatory responses associated with metabolic switches and changes in phenotypes and function of immune cell subsets. Obesity poses new health problems especially when it occurs in the context of other diseases, many of them frequently affect elderly subjects. An emerging problem is the decreased proportion of patients with obesity achieving clinical response to therapy. In this review, we will discuss the reciprocal influences of immune cell and AT inflammation in aging and age-associated diseases and the complex relationship of nutrient and energy-sensing homeostatic checkpoints, which contribute to shape the phenotype of the AT. We will specifically examine type-2 diabetes, rheumatoid arthritis, osteoarthritis, cognitive impairment, and dementia, where obesity plays a significant role, also in shaping some clinical aspects.
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- 2017
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22. Leukocyte-derived ratios are associated with late-life any type dementia: a cross-sectional analysis of the Mugello study
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Alex Ireland, Sandro Sorbi, Michele Abate, Angelo Di Iorio, Francesca Cecchi, Claudio Macchi, Roberto Paganelli, Raffaele Molino-Lova, Gemma Lombardi, and Raffaello Pellegrino
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Male ,Aging ,medicine.medical_specialty ,Immunosenescence ,Cross-sectional study ,Dementia ,Inflamm-aging ,Lymphocyte count ,Lymphocyte-to-monocyte-ratio ,Neuroinflammation ,Aged, 80 and over ,Cross-Sectional Studies ,Female ,Humans ,Monocytes ,Retrospective Studies ,Nonagenarians ,White blood cell ,Internal medicine ,medicine ,Mass index ,Stroke ,business.industry ,Confounding ,medicine.disease ,medicine.anatomical_structure ,Cohort ,Original Article ,Geriatrics and Gerontology ,business ,Body mass index - Abstract
Immunosenescence, vascular aging, and brain aging, all characterized by elevated levels of inflammatory markers, are thought to share a common pathogenetic pathway: inflamm-aging. Retrospective cross-sectional analysis was conducted using data from the Mugello study (Tuscany, Italy), a representative Italian cohort of free-living nonagenarians. to assess the association between specific peripheral inflammation markers derived from white blood cell counts, and the diagnosis of dementia. All the variables of interest were reported for 411 subjects (110 males and 301 females) out of 475 enrolled in the study. Anamnestic dementia diagnosis was obtained from clinical certificate and confirmed by a General Practitioner, whereas leukocyte ratios were directly calculated from white blood cell counts. Body mass index and comorbidities were considered potential confounders. Diagnosis of any type dementia was certified in 73 cases (17.8%). Subjects affected by dementia were older, more frequently reported a previous stroke, had lower body mass index, and lower Mini-Mental-State-Examination score. Moreover, they had a higher lymphocyte count and lymphocyte-to-monocyte ratio compared to the non-demented nonagenarians. We found that higher levels of lymphocyte counts are cross-sectionally associated with a clinical diagnosis of dementia. Furthermore, lymphocyte-to-monocyte ratio is directly associated with any type of dementia, independently of age, sex, lymphocyte count, and comorbidities. Lymphocyte-to-monocyte ratio may be considered a marker of immunological changes in the brain of dementia patients; moreover, it is low-cost, and easily available, thus enabling comparisons among different studies and populations, although the timeline and the extent of lymphocyte-to-monocyte ratio role in dementia development must be further investigated.
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- 2021
23. IgE sensitization profile in patients with Netherton syndrome
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Enrico Scala, Angelo Giuseppe Condorelli, Alessandro Scala, Elisabetta Caprini, Biagio Didona, Roberto Paganelli, and Daniele Castiglia
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Immunology ,Immunology and Allergy ,General Medicine - Abstract
Background: Scant data are currently available on the allergen-specific immunoglobulin (Ig)E sensitization profile in primary immunodeficiencies with hyper IgE. Netherton syndrome (NS, OMIM 266500) is an extremely rare form of congenital ichthyosis characterized by congenital scaly erythroderma, hair abnormalities, and deregulated IgE reactivity associated with severe atopic manifestations. Objective: The aim of this study was to evaluate the feasibility and reliability of a multiplex proteomic approach in the detection of specific IgE in NS. Methods: Specific IgE was evaluated in 10 individuals with an established molecular diagnosis of NS using an allergenic molecules microarray (immuno-solid-phase allergen chip). Results: Polireactivity to airway allergens, mainly house dust mites and olive tree pollen, and food allergens were observed in NS. Eighty per cent of patients were responsive to LTP or profilins. A clinical history suggestive of severe egg, milk, and fish allergy was confirmed by reactivity to the thermostable molecules Gal d 1, Bod 8, and parvalbumin Gad c 1, respectively. Latex reactivity was associated with Hev b 5 and 6 reactivity. Two distinct clusters of reactivity were observed after hierarchical analysis. Extremely high IgE levels (> 10,000 kU/L) do not affect the results obtained with microarrays. Conclusion: IgE multiplex evaluation allows (i) to profile IgE polyreactivity pictures, in the presence of LTP and profilin sensitization, (ii) to verify the clinical history of food allergy to milk, egg, and seafood, (iii) to confirm the allergic events associated with latex exposure, and (iv) to disclose the presence of preclinical sensitizations in patients affected by primary immunodeficiencies with hyper IgE, such as the NS.
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- 2022
24. Peripheral effector memory regulatory T cells are incremented and functionally enhanced in successful mite monomeric allergoid sublingual immunotherapy
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Takemi Otzuki, Laura Pierdomenico, Marco Marchisio, Paola Lanuti, Gianni Mistrello, Claudia Petrarca, Enrico Compalati, Sabrina Di Pillo, Mario Di Gioacchino, Roberto Paganelli, and Marianna Immacolata Petrosino
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Mites ,Sublingual Immunotherapy ,Effector ,Plant Extracts ,Immunology ,Rhinitis, Allergic, Seasonal ,Biology ,Allergens ,biology.organism_classification ,T-Lymphocytes, Regulatory ,Peripheral ,Allergoid ,Desensitization, Immunologic ,Mite ,Allergoids ,Immunology and Allergy ,Animals ,Humans ,Sublingual immunotherapy ,Letters to the Editor ,Letter to the Editor - Published
- 2020
25. Vernal Keratoconjunctivitis: A Case of Anti-IgE Treatment with Short-Lasting Remission
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Gilda Scarano, Roberto Paganelli, Alessia Gatta, E. Cavallucci, Mario Di Gioacchino, Arianna Lumaca, Loredana Della Valle, and Anila Farinelli
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Intraocular pressure ,medicine.medical_specialty ,Case Report ,Disease ,Omalizumab ,Immunoglobulin E ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,lcsh:Ophthalmology ,medicine ,0101 mathematics ,giant papillae ,Adverse effect ,biology ,business.industry ,010102 general mathematics ,corneal ulcer ,medicine.disease ,Dermatology ,eye diseases ,Tacrolimus ,Ophthalmology ,lcsh:RE1-994 ,030221 ophthalmology & optometry ,biology.protein ,omalizumab ,ige ,business ,Vernal keratoconjunctivitis ,medicine.drug - Abstract
Vernal keratoconjunctivitis (VKC) is a persistent, severe allergic eye disease, mainly occurring in children, that can lead to severe ocular complications including visual loss. The underlying etiology and pathophysiology of VKC remain unclear. Common therapies include topical antihistamines and mast cell stabilizers that are effective in mild-to-moderate forms of VKC but are often ineffective in severe forms that require topical or systemic corticosteroids. Dependence on steroids is common with potential adverse effects both local, as increased intraocular pressure, glaucoma, infection and cataract, as well as systemic ones, as reduction in child growth velocity. Alternative therapies are immunosuppressive drugs, like cyclosporine A and tacrolimus, that usually are effective but may also cause adverse effects. A promising therapeutic option is omalizumab, a recombinant anti-IgE humanized monoclonal antibody, currently used as add-on therapy for moderate to severe uncontrolled allergic asthma and chronic spontaneous urticaria. Here, we report the short-time duration of effective relief of symptoms after the prolonged use of omalizumab in a patient affected by refractory VKC. However, in our case any apparent beneficial effect was short lasting, and we propose that the duration of the disease and the concomitant long-term use of steroids leads to iatrogenic damage; thus, the disease becomes refractory to anti-IgE treatment.
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- 2020
26. Serological landscape of cytokines in cutaneous melanoma
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Pamela Di Giovanni, Federico Garbarino, Matteo Auriemma, Alessia Paganelli, Marika D'Urbano, P. Toto, Paolo Amerio, Tommaso Staniscia, Giuseppe Di Martino, Fabrizio Panarese, and Roberto Paganelli
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Male ,Cancer Research ,Chemokine ,Skin Neoplasms ,medicine.medical_treatment ,biomarkers ,cancer immunology ,chemokines ,Cytokines ,melanoma ,Adult ,Aged ,Biomarkers, Tumor ,Case-Control Studies ,Chemokine CCL3 ,Chemokine CCL4 ,Disease Progression ,Female ,Healthy Volunteers ,Humans ,Interferon-gamma ,Interleukin-10 ,Interleukin-4 ,Melanoma ,Middle Aged ,Neoplasm Staging ,Tumor ,biology ,05 social sciences ,General Medicine ,Primary tumor ,Cytokine ,Oncology ,050104 developmental & child psychology ,CCL3 ,Genetics ,medicine ,0501 psychology and cognitive sciences ,0505 law ,business.industry ,Cancer ,medicine.disease ,Tumor progression ,Cutaneous melanoma ,Immunology ,050501 criminology ,biology.protein ,business - Abstract
Background To date, serological markers to monitor melanoma progression and response to therapy are lacking. In this context cytokines appear to be promising biomarkers of the disease. Objective To compare cytokine and chemokine levels in melanoma patients and in healthy controls and to assess possible variations according to melanoma stage. Methods Serum chemokine and cytokine levels were determined by ELISA in 34 patients diagnosed histologically of malignant melanoma. Seven healthy volunteers were used as controls. Results We found a subset of cytokines (CCL3, CCL4, IFN-γ and IL-10) to be significantly higher in melanoma patients than in control group, thus confirming the importance of the inflammation in cancer. While CCL3 increased with tumor progression, IFN-γ and IL-10 showed higher levels in stage I patients. Moreover, we noticed a direct correlation between CCL3 level and the presence of ulceration in the primary tumor; on the contrary, CCL4, IL-10 and IFN-γ were lowered down in patients with ulcerated melanoma. Conclusions These results expand and confirm observations made in other studies focusing on a more limited number of molecules. This extended panel of cytokines examines the potential roles of type2 cytokines (such as IL-4) and many chemokines (mainly CCL3) as biomarkers in melanoma progression.
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- 2019
27. Improvement of Inflammation and Pain After Three Months’ Exclusion Diet in Rheumatoid Arthritis Patients
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Guagnano Maria Teresa, D’Angelo Chiara, Caniglia Daniela, Celletti Eleonora, Emanuela Sabatini, Speranza Lorenza, Bucci Marco, Cipollone Francesco, and Roberto Paganelli
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Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help, to manage the symptoms of RA, by lowering inflammation, and potentially decreasing pain.Methods: In 40 patients with long standing RA, with stable symptoms, and treated with conventional (c-) and biological (b-) Disease modifying anti-rheumatic drugs (DMARDs), the effect of 3-months’ diet avoiding meat, gluten, and lactose (privative diet) was evaluated in comparison with a control balanced diet including those foods. Patients choosing the exclusion diet were followed in parallel to an equal number of patients on their normal diet, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0 a blood sample was collected for laboratory tests, and anthropometric measurements were recorded. These evaluations were repeated at the end of the 3 months’dietary regimens.Results: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients following the avoidance diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values, however the change was significant only for the exclusion diet. With either diet, patients showed significant decreases of body weight and body mass index (BMI), with a reduction of waist and hips circumferences, lower basal glucose and circulating leptin levels. Exclusion diet was also able to significantly reduce systolic (SYS) (p=0.002) and diastolic (DIA) (p=0.027) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein (CRP) were also significantly decreased after 3 months of the meat-, lactose, and gluten-free diet.Conclusions: Our results suggest that an exclusion diet can result in a better control of inflammation and pain in RA patients under stable optimized drug treatment.
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- 2021
28. A case of vaccine-induced immune thrombotic thrombocytopenia with massive artero-venous thrombosis
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Maria Costanza, Turi, Francesca, Spitaleri, Anna M, Gori, Giustino, Parruti, Angela A, Rogolino, Alberto, Albani, Betti, Giusti, Luciano, Agostinone, Francesca, Cesari, Paola, Ranalli, Stefano, Pulini, Giorgia, Di Gioacchino, Roberto, Paganelli, and Rossella, Marcucci
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Venous Thrombosis ,Purpura, Thrombocytopenic, Idiopathic ,Vaccines ,Humans ,Thrombosis ,Thrombocytopenia ,Haemostasis and Thrombosis - Published
- 2021
29. Kounis Syndrome as First Manifestation of Allergic Sensitization
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Anila Farinelli, Gilda Scarano, Daniele Forlani, Arianna Lumaca, L Della Valle, M Di Marco, Roberto Paganelli, Claudia Petrarca, Alberto D’Alleva, L Di Giampaolo, M. Di Gioacchino, Alessia Gatta, and Leonardo Paloscia
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Acute coronary syndrome ,medicine.medical_specialty ,Ischemia ,lcsh:Medicine ,Case Report ,Tryptase ,Kounis syndrome ,030204 cardiovascular system & hematology ,Chest pain ,Angina ,Allergic sensitization ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030212 general & internal medicine ,biology ,business.industry ,lcsh:R ,General Medicine ,medicine.disease ,biology.protein ,Cardiology ,medicine.symptom ,business ,Anaphylaxis - Abstract
Mast cells are abundant in the heart, among myocardial fibers, around coronary arteries, within arterial intima and intramural vessels, and in atherosclerotic plaques. Their mediators can be released during anaphylaxis and be responsible for acute coronary syndrome. This condition has been described as Kounis syndrome (KS). We report three cases of acute myocardial ischemia, which fulfill the definition for KS. In Cases 1 and 2, the association of intense chest pain with acute urticaria after an allergenic contact (wasp sting and betalactam antibiotic administration, respectively) was suspected to be an attack of angina related to an allergic reaction. No signs of an allergic reaction were observed in Case 3, but only the history of a wasp sting suggested its relationship to loss of consciousness and heart ischemia when hypersensitivity to venom was ascertained. These cases strongly recommend measurement of anaphylactic biomarkers, such as tryptase, during acute coronary syndromes to detect the possible involvement of an allergic reaction. Conversely, measurement of cardiac biomarkers during anaphylaxis, even without obvious signs of myocardial ischemia, might identify patients at risk of myocardial injury.
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- 2019
30. Omalizumab in chronic spontaneous urticaria: steroid sparing effect
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Loredana Della Valle, Roberto Paganelli, E. Cavallucci, Mario Di Gioacchino, Anila Farinelli, and Alessia Gatta
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,business.industry ,Dermatology ,Omalizumab ,Steroid treatments ,Discontinuation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,Steroid use ,Steroid sparing ,Medicine ,business ,Adverse effect ,Beneficial effects ,medicine.drug - Abstract
Omalizumab has been recognized to be effective in the treatment of chronic spontaneous urticaria (CSU). The Italian Medicines Agency authorizes two omalizumab courses, only for patients with CSU unresponsive to antihistamines, and this schedule may limit omalizumab use. Unfortunately, in the majority of CSU, the schedule is unsatisfactory because symptoms usually recur shortly after discontinuation of treatment. A case of a patient needing more than two treatment courses with omalizumab is reported, in order to discuss the rationale for its long-term use. Patient had needed systemic steroids almost continuously for 4 years. Two severe glucocorticoid-associated adverse events (GAEs) occurred during long-term treatment. Omalizumab 300 mg monthly was started with immediate disappearance of the urticarial lesions. Beneficial effects waned shortly after discontinuation of treatment, and further steroid use was needed. A second omalizumab course showed the same clinical pattern, with prompt response and recurrence of symptoms after suspension. Therefore, we decided to repeat the 6 months omalizumab treatment as soon as symptoms recurred, to avoid further emergency steroid treatments and GAEs. This experience suggests that long-term use of omalizumab could be useful. Evidences show that omalizumab is effective and safe for re-treatment and long-term use of responding patients after recurrence.
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- 2018
31. Total urinary polyphenols and longitudinal changes of bone properties. The InCHIANTI study
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Stefano Volpato, Antonella Cherubini, A. Di Iorio, Roberto Paganelli, Stefania Bandinelli, Giovanni Barassi, Michele Abate, Cristina Andres-Lacueva, Raul Zamora-Ros, and Luigi Ferrucci
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0301 basic medicine ,medicine.medical_specialty ,Longitudinal study ,Endocrinology, Diabetes and Metabolism ,Urinary system ,Socio-culturale ,Physiology ,030209 endocrinology & metabolism ,Antioxidants ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Urinary polyphenols ,Bone Density ,Internal medicine ,medicine ,Ossos ,Humans ,Bone ,Bone-pQCT ,Dietary polyphenols ,Bones ,business.industry ,Osteoporosi ,Osteoporosis prevention ,food and beverages ,Polyphenols ,Micronutrient ,Rheumatology ,Diet ,medicine.anatomical_structure ,Italy ,Polyphenol ,Polifenols ,Cohort ,Osteoporosis ,Cortical bone ,Original Article ,030101 anatomy & morphology ,business - Abstract
Summary The aim of this study was to evaluate the association of levels of urinary total polyphenols considered as a proxy measure of polyphenol intake, with longitudinal changes of bone properties, in the InCHIANTI study. Dietary intake of polyphenols appears to be associated with future accelerated deterioration of bone health. Introduction Polyphenols, micronutrients ingested through plant-based foods, have antioxidant and anti-inflammatory properties and may contribute to osteoporosis prevention. We evaluated associations of high levels of urinary total polyphenols (UTP), a proxy measure of polyphenol intake, with longitudinal changes of bone properties in a representative cohort of free-living participants of the InCHIANTI study. Methods The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998 and follow-up visits in 2001 and 2004. Of the 1453 participants enrolled, 956 consented to donate a 24-h urine sample used to assess UTP, had dietary assessment, a physical examination, and underwent a quantitative computerized tomography (pQCT) of the tibia. From pQCT images, we estimated markers of bone mass (BM), diaphyseal design (DD), and material quality (MQ). Mixed models were used to study the relationship between baseline tertiles of UTP with changes of the bone characteristics over the follow-up. Results At baseline, higher levels of UTP were positively correlated with markers of BM, DD, and MQ. Compared with lower tertile of UTP, participants in the intermediate and highest tertiles had higher cortical bone area, cortical mineral content, and cortical thickness. However, participants in the intermediate and highest UTP tertiles experienced accelerated deterioration of these same parameters over the follow-up compared with those in the lowest UTP tertile. Conclusions Dietary intake of polyphenols estimated by UTP and dietary questionnaire was associated with long-term accelerated deterioration of bone health. Our study does not support the recommendation of increasing polyphenol intake for osteoporosis prevention.
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- 2021
32. Exploratory study on immune phenotypes in Alzheimer's disease and vascular dementia
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G. Pawelec, A. Di Iorio, Chiara D'Angelo, D. Goldeck, Roberto Paganelli, and L. Gaspari
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chemical and pharmacologic phenomena ,Inflammation ,Pilot Projects ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Alzheimer Disease ,mental disorders ,medicine ,Dementia ,Humans ,030212 general & internal medicine ,IL-2 receptor ,Vascular dementia ,Amyloid beta-Peptides ,business.industry ,Dementia, Vascular ,FOXP3 ,CD28 ,hemic and immune systems ,medicine.disease ,Phenotype ,Neurology ,Immunology ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,CD8 - Abstract
Background and purpose The differentiation of Alzheimer's disease (AD) dementia from vascular dementia (VaD) and mixed-type dementia (mixed dementia) requires stepwise analysis and usually occurs late in the disease process. Early diagnosis and therapy monitoring would benefit greatly from the identification of biomarkers of neurodegeneration, especially blood biomarkers. To this end, the aim of the present pilot study was to investigate differences in the distribution of peripheral T-cell populations in patients with AD compared to VaD and mixed dementia. Methods Flow cytometry was performed on blood samples from 11 patients with AD, six with VaD and six with mixed dementia, as well as 17 healthy control subjects (HCs). CD4+ and CD8+ T cells were typed for expression of CD45, CD27, CD28, CD25, FoxP3, CCR4 and CCR6; the other leukocytes were also assessed. Functionally, immune cell uptake of the β-amyloid (Aβ) toxic fragment (Aβ1-42 ) was also evaluated. Results A higher proportion of CD4+CD28- memory T cells and a reciprocal reduction of CD4+CD28+CD27+ naive T lymphocytes was detected in all patient groups relative to controls. Significantly fewer CD4+CD25+FoxP3 regulatory T cells were present in patients with VaD, and significantly more CCR6+ and CCR4+ CD4+ T cells in those with AD. Higher CCR6+ T-cell frequencies were also present in patients with mixed dementia, potentially due to the inflammation and immune cell chemoattraction triggered by Aβ. Conclusions The present study was a comprehensive investigation comparing different kinds of dementia, revealing differentially expressed peripheral markers that are potentially useful for early AD, VaD and mixed dementia diagnoses, and that would assist in proper treatments for these disparate diseases. Validation is now required.
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- 2020
33. Nanoparticle-based immunotherapy: state of the art and future perspectives
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Pietro Del Biondo, Alessia Gatta, Luca Di Giampaolo, Gilda Scarano, Loredana Della Valle, Anila Farinelli, Arianna Lumaca, Mario Di Gioacchino, Roberto Paganelli, and Claudia Petrarca
- Subjects
Allergen immunotherapy ,Allergy ,Drug Carriers ,business.industry ,medicine.medical_treatment ,fungi ,Immunology ,technology, industry, and agriculture ,food and beverages ,Nanoparticle ,Nanotechnology ,macromolecular substances ,Immunotherapy ,medicine.disease ,Adjuvants, Immunologic ,medicine ,Hypersensitivity ,Immunology and Allergy ,Animals ,Humans ,Nanoparticles ,business ,Adjuvant - Abstract
For several years now, medicine has been benefiting from the contribution of nanoparticles (NPs) technology for both diagnosis and therapy. They can be used as adjuvants, being capableThe review focuses on experimental use of NPs as adjuvants/carriers for allergen immunotherapy (AIT). Human clinical trials conducted so far are discussed.Results of experimental studies and recent clinical trials support the use of NPs as carrier/adjuvant in AIT. Comparisons between NP-based and classical AIT are needed, to show the usefulness of the NP-based approach. However, there are still unsolved problems: the persistence of non-degradable NPs with possible toxicological consequences, and the formation of the protein corona around the NPs, which could alter their activity and fate. Virus-like particles seem the most promising NPs for allergy treatment, as for other vaccines. Over the next decade, NP-based AIT will be largely used to treat allergic disorders.
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- 2020
34. Contributors
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Michael S. Abers, Daria V. Babushok, Mark Ballow, Bertrand Boisson, Vincent Robert Bonagura, Francisco A. Bonilla, João Bosco de Oliveira Filho, Kaan Boztug, Lori Broderick, Manish J. Butte, Fabio Candotti, Jean-Laurent Casanova, Shanmuganathan Chandrakasan, Antonio Condino-Neto, Yanick J. Crow, Charlotte Cunningham-Rundles, Virgil A.S.H. Dalm, Adriana A. de Jesus, Emma de Maio, Geneviève de Saint Basile, Esther de Vries, Inderjeet Dokal, Christopher J.A. Duncan, A. Durandy, Stephan Ehl, Amos Etzioni, Polly J. Ferguson, Thomas A. Fleisher, Lisa R. Forbes-Satter, Michael M. Frank, Alexandra F. Freeman, Marie-Louise Frémond, John W. Frew, Mathieu Fusaro, Eleonora Gambineri, Rebecca D. Ganetzky, Andrew R. Gennery, Raphaela Goldbach-Mansky, Amy C. Goldstein, John M. Graham, Stephanie E. Gupton, Elie Haddad, Sophie Hambleton, Eric P. Hanson, Jennifer Heimall, Miep Helfrich, Sarah E. Henrickson, Steven M. Holland, Amy P. Hsu, Soma Jyonouchi, Sara Kashef, Judith Kelsen, Maya Khalil, Christoph Klein, Lisa Kobrynski, Donald B. Kohn, S. Kracker, James G. Krueger, Pascal M. Lavoie, Heather K. Lehman, Jennifer W. Leiding, Michael J. Lenardo, Ofer Levy, Allison Pecha Lim, Michail S. Lionakis, Andrea Lisco, Vassilios Lougaris, Saul O. Lugo Reyes, M. Louise Markert, Rebecca A. Marsh, Elizabeth A. McCarthy, Isabelle Meyts, Cinzia Milito, Joshua D. Milner, Jeffrey E. Ming, Despina Moshous, Ludmila Müller, Kristina Navrazhina, Kim E. Nichols, Luigi D. Notarangelo, Eric Oksenhendler, Jordan S. Orange, Roberto Paganelli, Graham Pawelec, Tancredi Massimo Pentimalli, Elena E. Perez, Capucine Picard, Alessandro Plebani, Oscar Porras, Amanda C. Przespolewski, Anne Puel, Federica Pulvirenti, Isabella Quinti, Nima Rezaei, Ger T. Rijkers, David Walter Rosenthal, Sergio D. Rosenzweig, Brahm H. Segal, Mikko R.J. Seppänen, Irini Sereti, Anna Shcherbina, Cristina Sobacchi, Jacqueline D. Squire, Polina Stepensky, Helen C. Su, Kathleen E. Sullivan, Troy R. Torgerson, Gulbu Uzel, Mirjam van der Burg, Anna Villa, Jean-Pierre de Villartay, Klaus Warnatz, Richard L. Wasserman, Corry M.R. Weemaes, Joyce E. Yu, Shen-Ying Zhang, and John B. Ziegler
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- 2020
35. Asplenia
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Federica Pulvirenti, Emma de Maio, Cinzia Milito, Roberto Paganelli, and Isabella Quinti
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- 2020
36. Thyroid hormone signaling is associated with physical performance, muscle mass, and strength in a cohort of oldest-old: results from the Mugello study
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Alex Ireland, Roberto Paganelli, Angelo Di Iorio, Raffaele Molino-Lova, Francesca Cecchi, Claudio Macchi, Giovanni Barassi, and Michele Abate
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0301 basic medicine ,Male ,medicine.medical_specialty ,Aging ,Thyroid Hormones ,Levothyroxine ,Oldest-old ,030209 endocrinology & metabolism ,Physical performance ,03 medical and health sciences ,0302 clinical medicine ,Thyroid hormone signaling ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Muscle mass ,Muscle strength ,Rehabilitation ,Aged, 80 and over ,Hand Strength ,business.industry ,Thyroid ,Confounding ,Skeletal muscle ,Physical Functional Performance ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Cross-Sectional Studies ,Quartile ,Italy ,Cohort ,Population study ,Original Article ,Female ,Geriatrics and Gerontology ,business ,medicine.drug - Abstract
Thyroid hormones (THs) play a crucial role in the homeostasis of muscle function, such as myogenesis and energy metabolism, suggesting that the thyroid may be also involved in the entropic processes of muscle aging. The aim of the present study is to evaluate the effect of TH signaling on physical performance, muscle mass, and strength in a cohort of community-dwelling oldest-old subjects (> 90 years). The study population was selected in a rural area of central Italy (Mugello, Tuscany), and the design was cross-sectional. Four hundred seventy-five subjects (130 males and 345 females) were enrolled, representing about 65% of all the nonagenarians living in the Mugello area. After adjusting for multiple confounding factors (sex, age, diabetes, and levothyroxine administration), the lowest quartile of FT3/FT4 ratio distribution showed lower physical performance compared to the other quartiles (β ± SE: − 0.49 ± 0.12; p β ± SE: 1.11 ± 0.42; p = 0.009). In addition, the lowest quartile of FT4 showed a statistically significant higher handgrip strength (β ± SE: 1.78 ± 0.68; p = 0.009) compared to all other quartiles. This study demonstrates that nonagenarians with higher FT3/FT4 ratios had better preserved muscle function, therefore successfully overcoming the imbalance of homeostatic and entropic processes involved in muscle aging. However, we could not establish a cause-effect relationship due to the cross-sectional design of the study.
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- 2020
37. The Italian Registry for Primary Immunodeficiencies (Italian Primary Immunodeficiency Network; IPINet): Twenty Years of Experience (1999–2019)
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A G Ugazio, Giovanna Russo, Maria Giovanna Danieli, Alberto Tommasini, Maria Cristina Pietrogrande, Raffaele Badolato, Andrea Pession, Carlo Agostini, Fabio Cardinale, Eleonora Gambineri, Baldassare Martire, Adele Civino, Manuela Baronio, Marco Gattorno, Marco Zecca, Viviana Moschese, Chiara Azzari, Alessio Benvenuto, Marzia Duse, Antonino Trizzino, Luisa Gazzurelli, Isabella Quinti, Vassilios Lougaris, Andrea Matucci, Giuseppe Spadaro, Claudio Lunardi, Angelo Vacca, Roberto Rondelli, Maria Caterina Putti, Luciana Chessa, Giovanna Fabio, Andrea Biondi, Fausto Cossu, Roberto Paganelli, Paolo Rossi, Rita Consolini, Alessandro Aiuti, Gian Luigi Marseglia, Luigi Carpino, Caterina Cancrini, Maddalena Marinoni, Silvana Martino, Claudio Pignata, Annarosa Soresina, Patrizia Bertolini, Alessandro Plebani, Lougaris, V., Pession, A., Baronio, M., Soresina, A., Rondelli, R., Gazzurelli, L., Benvenuto, A., Martino, S., Gattorno, M., Biondi, A., Zecca, M., Marinoni, M., Fabio, G., Aiuti, A., Marseglia, G., Putti, M. C., Agostini, C., Lunardi, C., Tommasini, A., Bertolini, P., Gambineri, E., Consolini, R., Matucci, A., Azzari, C., Danieli, M. G., Paganelli, R., Duse, M., Cancrini, C., Moschese, V., Chessa, L., Spadaro, G., Civino, A., Vacca, A., Cardinale, F., Martire, B., Carpino, L., Trizzino, A., Russo, G., Cossu, F., Badolato, R., Pietrogrande, M. C., Quinti, I., Rossi, P., Ugazio, A., Pignata, C., Plebani, A., Lougaris, V, Pession, A, Baronio, M, Soresina, A, Rondelli, R, Gazzurelli, L, Benvenuto, A, Martino, S, Gattorno, M, Biondi, A, Zecca, M, Marinoni, M, Fabio, G, Aiuti, A, Marseglia, G, Putti, M, Agostini, C, Lunardi, C, Tommasini, A, Bertolini, P, Gambineri, E, Consolini, R, Matucci, A, Azzari, C, Danieli, M, Paganelli, R, Duse, M, Cancrini, C, Moschese, V, Chessa, L, Spadaro, G, Civino, A, Vacca, A, Cardinale, F, Martire, B, Carpino, L, Trizzino, A, Russo, G, Cossu, F, Badolato, R, Pietrogrande, M, Quinti, I, Rossi, P, Ugazio, A, Pignata, C, and Plebani, A
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Primary immunodeficiencies ,Adolescent ,Databases, Factual ,Primary Immunodeficiency Diseases ,Immunology ,Age at diagnosis ,History, 21st Century ,Combined immunodeficiencies ,Young Adult ,Medical microbiology ,patient registry ,Epidemiology ,medicine ,Prevalence ,Immunology and Allergy ,Humans ,Registries ,Geography, Medical ,Child ,Adult patients ,business.industry ,Infant, Newborn ,Infant ,History, 20th Century ,medicine.disease ,Prognosis ,Settore MED/38 ,Natural history ,Italy ,Child, Preschool ,Population Surveillance ,Cohort ,Primary immunodeficiency ,Original Article ,Female ,business - Abstract
Primary immunodeficiencies (PIDs) are heterogeneous disorders, characterized by variable clinical and immunological features. National PID registries offer useful insights on the epidemiology, diagnosis, and natural history of these disorders. In 1999, the Italian network for primary immunodeficiencies (IPINet) was established. We report on data collected from the IPINet registry after 20 years of activity. A total of 3352 pediatric and adult patients affected with PIDs are registered in the database. In Italy, a regional distribution trend of PID diagnosis was observed. Based on the updated IUIS classification of 2019, PID distribution in Italy showed that predominantly antibody deficiencies account for the majority of cases (63%), followed by combined immunodeficiencies with associated or syndromic features (22.5%). The overall age at diagnosis was younger for male patients. The minimal prevalence of PIDs in Italy resulted in 5.1 per 100.000 habitants. Mortality was similar to other European registries (4.2%). Immunoglobulin replacement treatment was prescribed to less than one third of the patient cohort. Collectively, this is the first comprehensive description of the PID epidemiology in Italy.
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- 2020
38. Improvement of Inflammation and Pain after Three Months’ Exclusion Diet in Rheumatoid Arthritis Patients
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Pamela Di Giovanni, Daniela Caniglia, Roberto Paganelli, Emanuela Sabatini, Francesco Cipollone, M. Bucci, Chiara D'Angelo, Lorenza Speranza, Eleonora Celletti, and Maria Teresa Guagnano
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Adult ,rheumatoid arthritis ,medicine.medical_specialty ,Visual Analog Scale ,Visual analogue scale ,Adipokine ,Overweight ,leptin ,Gastroenterology ,Article ,Arthritis, Rheumatoid ,Adipokines ,Quality of life ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,pain ,meat- gluten- and lactose-exclusion diet ,TX341-641 ,Aged ,Nutrition and Dietetics ,Nutrition. Foods and food supply ,business.industry ,Leptin ,bioimpedance analysis ,dietary regimen ,Middle Aged ,medicine.disease ,Blood pressure ,inflammation ,Rheumatoid arthritis ,Cytokines ,Patient Compliance ,Female ,medicine.symptom ,business ,Body mass index ,Food Science - Abstract
Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. Methods: In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products, privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months’ dietary regimens. Results: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values, however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. Conclusions: Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.
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- 2021
39. Periodontal Ligament Stem Cells: Current Knowledge and Future Perspectives
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Alessia Paganelli, Emanuela Mazzon, Marco Marchisio, Francesca Diomede, Jacopo Pizzicannella, Oriana Trubiani, Sergio Caputi, and Roberto Paganelli
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0301 basic medicine ,Adult ,Periodontal ligament stem cells ,Periodontal Ligament ,Cells ,regenerative medicine ,MSCs ,Biology ,Regenerative Medicine ,Regenerative medicine ,03 medical and health sciences ,0302 clinical medicine ,Periodontal fiber ,Animals ,Humans ,Regeneration ,Cells, Cultured ,Cell Proliferation ,Cultured ,EAE ,Regeneration (biology) ,Stem Cells ,Mesenchymal stem cell ,Cell Differentiation ,Cell Biology ,Hematology ,In vitro ,Cell biology ,inflammation ,periodontal ligament ,stem cells ,Stem Cell Transplantation ,030104 developmental biology ,Stem cell ,030217 neurology & neurosurgery ,Developmental Biology ,Adult stem cell - Abstract
Teeth represent a fascinating area of study in regenerative medicine, because of their unique and complex developmental origin. Several types of mesenchymal stem cells (MSCs) have been characterized in the oral cavity, and those derived from the periodontal ligament (PDL) first isolated by our group in 2005, can be expanded in a xeno-free medium preserving morphological features and markers associated with pluripotency. These postnatal MSCs can be easily recovered by noninvasive procedures and cultured. This could facilitate the use of adult stem cells in human clinical regeneration therapy. In this review we summarize the results of our studies describing morphofunctional features, surface markers, and multilineage differentiation capacity in vitro of PDL MSCs obtained in our laboratories. In vivo characterization of PDL stem cell (PDLSC) location and heterogeneity are still lacking. However, we describe studies exploring the potential use of PDLSC to treat both periodontal diseases and regeneration of other tissues. These MSCs may have an advantage in possessing also angiogenetic, immunoregulatory, and anti-inflammatory properties. The secretome of such cells contains several interesting molecules mimicking the effects of the producer cells. We describe some recent studies from our group on the use of conditioned medium from PDL MSCs, and purified extracellular vesicles therein contained, in animal models of experimental autoimmune encephalomyelitis and their potential application to human disease.
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- 2019
40. Biological clocks: their relevance to immune-allergic diseases
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Mario Di Gioacchino, Roberto Paganelli, and Claudia Petrarca
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Melanopsin ,Allergy ,Chronopharmacology ,Shift work ,Immunology ,Review ,Retinal ganglion ,03 medical and health sciences ,Immune system ,Immunology and Allergy ,Medicine ,Circadian rhythm ,Molecular Biology ,Chronobiology ,business.industry ,Suprachiasmatic nucleus ,Biological clock ,030104 developmental biology ,Cytokine secretion ,lcsh:RC581-607 ,business ,Neuroscience - Abstract
The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made in the past 15 years on the genetic and molecular mechanisms regulating many physiological functions, has renewed the attention to the importance of circadian rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus in the brain, photoentrained via direct connection with melanopsin containing, intrinsically light-sensitive retinal ganglion cells, and it projects to periphery, thus creating an inner circadian rhythm. This regulates several activities, including sleep, feeding times, energy metabolism, endocrine and immune functions. Disturbances of these rhythms, mainly of wake/sleep, hormonal secretion and feeding, cause decrease in quality of life, as well as being involved in development of obesity, metabolic syndrome and neuropsychiatric disorders. Most immunological functions, from leukocyte numbers, activity and cytokine secretion undergo circadian variations, which might affect susceptibility to infections. The intensity of symptoms and disease severity show a 24 h pattern in many immunological and allergic diseases, including rheumatoid arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is accompanied by altered sleep duration and quality, a major determinant of quality of life. Shift work and travel through time zones as well as artificial light pose new health threats by disrupting the circadian rhythms. Finally, the field of chronopharmacology uses these concepts for delivering drugs in synchrony with biological rhythms.
- Published
- 2018
41. The role of miRNAs in autoimmune inflammatory diseases
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Federica Canzano, Alessia Paganelli, Roberto Paganelli, and Paola Volpe
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology ,business.industry ,030220 oncology & carcinogenesis ,microRNA ,Immunology ,Medicine ,business - Published
- 2018
42. Aging, Obesity, and Inflammatory Age-Related Diseases
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Roberto Paganelli, Bonnie B. Blomberg, and Daniela Frasca
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,rheumatoid arthritis ,obesity ,Mini Review ,Immunology ,Context (language use) ,Inflammation ,Type 2 diabetes ,type-2 diabetes ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Immune system ,Diabetes mellitus ,medicine ,Dementia ,Immunology and Allergy ,030203 arthritis & rheumatology ,business.industry ,aging ,medicine.disease ,Obesity ,3. Good health ,030104 developmental biology ,inflammation ,medicine.symptom ,business ,lcsh:RC581-607 - Abstract
The increase in the prevalence of obesity represents a worldwide phenomenon in all age groups and is pathologically and genetically correlated with several metabolic and cardiovascular diseases, representing the most frequent age-related diseases. Obesity superimposed on aging drastically increases chronic low-grade inflammation (inflammaging), which is an important link between obesity, insulin resistance, and age-associated diseases. Immune cells of both the innate and the adaptive immune systems infiltrate the adipose tissue (AT) and during obesity induce inflammatory responses associated with metabolic switches and changes in phenotypes and function of immune cell subsets. Obesity poses new health problems especially when it occurs in the context of other diseases, many of them frequently affect elderly subjects. An emerging problem is the decreased proportion of patients with obesity achieving clinical response to therapy. In this review, we will discuss the reciprocal influences of immune cell and AT inflammation in aging and age-associated diseases and the complex relationship of nutrient and energy-sensing homeostatic checkpoints, which contribute to shape the phenotype of the AT. We will specifically examine type-2 diabetes, rheumatoid arthritis, osteoarthritis, cognitive impairment, and dementia, where obesity plays a significant role, also in shaping some clinical aspects.
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- 2017
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43. More than Meets the Eye: Biological Clocks
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Roberto Paganelli
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Computer science ,Biological clock ,Real-time computing - Published
- 2017
44. A Peculiar Molecular Profile of Umbilical Cord-Mesenchymal Stromal Cells Drives Their Inhibitory Effects on Multiple Myeloma Cell Growth and Tumor Progression
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Anna Caselli, Annalisa Savonarola, Marco Tucci, Antonella Valentina Tamma, Franco Silvestris, Giuseppe Loverro, Roberto Paganelli, and Sabino Ciavarella
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Stromal cell ,Carcinogenesis ,Cellular differentiation ,Adipose tissue ,Biology ,Mesenchymal Stem Cell Transplantation ,Umbilical Cord ,Mice ,Original Research Reports ,Animals ,Humans ,Progenitor cell ,Clonogenic assay ,Cell Proliferation ,Cell growth ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Hematology ,Gene Expression Regulation, Neoplastic ,Adipose Tissue ,Tumor progression ,Immunology ,Cancer research ,Multiple Myeloma ,Developmental Biology - Abstract
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are under intensive investigation in preclinical models of cytotherapies against cancer, including multiple myeloma (MM). However, the therapeutic use of stromal progenitors holds critical safety concerns due to their potential MM-supporting activity in vivo. Here, we explored whether MSCs from sources other than BM, such as adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs), affect MM cell growth in comparison to either normal (nBM-MSCs) or myelomatous marrow MSCs (MM-BM-MSCs). Results from both proliferation and clonogenic assays indicated that, in contrast to nBM- and MM-BM-MSCs, both AD and particularly UC-MSCs significantly inhibit MM cell clonogenicity and growth in vitro. Furthermore, when co-injected with UC-MSCs into mice, RPMI-8226 MM cells formed smaller subcutaneous tumor masses, while peritumoral injections of the same MSC subtype significantly delayed the tumor burden growing in subcutaneous plasmocytoma-bearing mice. Finally, both microarrays and ELISA revealed different expression of several genes and soluble factors in UC-MSCs as compared with other MSCs. Our data suggest that UC-MSCs have a distinct molecular profile that correlates with their intrinsic anti-MM activity and emphasize the UCs as ideal sources of MSCs for future cell-based therapies against MM.
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- 2015
45. Lipid transfer protein sensitization: reactivity profiles and clinical risk assessment in an Italian cohort
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O. De Pità, Lorenzo Cecchi, M. Giani, Damiano Abeni, E. C. Guerra, Enrico Scala, R Asero, L. Pirrotta, Roberto Paganelli, Stephen J. Till, and D. Pomponi
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Adult ,Male ,Allergy ,Adolescent ,Immunology ,Immunoglobulin E ,medicine.disease_cause ,Risk Assessment ,Severity of Illness Index ,Cohort Studies ,Young Adult ,Mugwort ,Pollen ,Hypersensitivity ,Prevalence ,medicine ,Cluster Analysis ,Humans ,Immunology and Allergy ,Child ,Sensitization ,Aged ,biology ,Microarray analysis techniques ,Allergens ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Italy ,Profilin ,Child, Preschool ,biology.protein ,Female ,Immunization ,Carrier Proteins ,Plant lipid transfer proteins ,Food Hypersensitivity - Abstract
Nonspecific lipid transfer proteins (nsLTPs) represent a major cause of systemic food allergic reactions in the Mediterranean area. This study investigate hierarchical patterns and cluster relationships of IgE sensitization to different nsLTPs, and the relationship to clinical allergy in a large Italian cohort.A total of 568 nsLTP-positive subjects after IgE ImmunoCAP-ISAC microarray analysis with Ara h 9, Art v 3, Cor a 8, Jug r 3, Pla a 3, Pru p 3 and Tri a 14 allergens were studied. IgE inhibition experiments were carried out with mugwort and plane tree pollen extracts.Eighty-two per cent of nsLTP-positive participants (94% if6 years old) were Pru p 3(pos) , and 71% were Jug r 3(pos) . Participants who reacted to5 nsLTPs reported a higher incidence of food-induced systemic reactions. Only Art v 3 and Pla a 3 (mugwort and plane tree nsLTPs, respectively) were associated with respiratory symptoms, and a correlation was observed between sensitization to pollen and plant food nsLTPs, particularly between Pla a 3 and tree nut/peanut nsLTPs. Co-sensitization to Par j 2 and PR-10 or profilin pan-allergens was associated with a lower prior prevalence of severe food-induced reactions. In inhibition assays, plane and mugwort pollen extracts inhibited 50-100% of IgE binding to food nsLTPs in microarrays.Testing IgE reactivity to a panel of nsLTP allergens unveils important associations between nsLTP sensitization profiles and clinical presentation and allows the identification of novel cluster patterns indicating likely cross-reactivities and highlighting potential allergens for nsLTP immunotherapy.
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- 2015
46. Allergic diseases in the elderly: biological characteristics and main immunological and non-immunological mechanisms
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Giorgio Walter Canonica, Stefano Del Giacco, Nicola Scichilone, Livio Simioni, Maria Teresa Ventura, Erminia Ridolo, Vincenzo Patella, Roberto Paganelli, Matteo Bonini, Paola Lucia Minciullo, Giovanni Passalacqua, Sebastiano Gangemi, Carlo Lombardi, Ventura M.T., Scichilone N., Paganelli R., Minciullo P.L., Patella V., Bonini M., Passalacqua G., Lombardi C., Simioni L., Ridolo E., Del Giacco S.R., Gangemi S., and Canonica G.W.
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0301 basic medicine ,Aging ,Allergy ,Urticaria ,medicine.medical_treatment ,Immunology ,Environmental pollution ,Review ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,03 medical and health sciences ,Elderly ,Immune system ,Anaphylaxi ,Food allergy ,medicine ,Immunology and Allergy ,Anaphylaxis ,Molecular Biology ,Asthma ,business.industry ,Conjunctiviti ,Immunotherapy ,Conjunctivitis ,medicine.disease ,Drug reaction ,030104 developmental biology ,age ,Life expectancy ,business - Abstract
Life expectancy and the number of elderly people are progressively increasing around the world. Together with other pathologies, allergic diseases also show an increasing incidence in geriatric age. This is partly due to the growing emphasis on a more accurate and careful diagnosis of the molecular mechanisms that do not allow to ignore the real pathogenesis of many symptoms until now unknown, and partly to the fact that the allergic people from 20 years ago represent the elderly population now. Moreover, environmental pollution predisposes to the onset of allergic asthma and dermatitis which are the result of internal pathologies more than the expression of allergic manifestations. At the same time the food contamination permits the onset of allergic diseases related to food allergy. In this review we provide the state of the art on the physiological changes in the elderly responsible for allergic diseases, their biological characteristics and the major immunological and extra immunological mechanisms. Much emphasis is given to the management of several diseases in the elderly, including anaphylactic reactions. Moreover, some new features are discussed, such as management of asthma with the support of physical activity and the use of the AIT as prevention of respiratory diseases and for the purpose of a real and long lasting benefit. The mechanisms of adverse reactions to drugs are also discussed, due to their frequency in this age, especially in polytherapy regimens. Study of the modifications of the immune system is also of great importance, as regards to the distribution of the lymphocytes and also the presence of a chronic inflammatory disease related to the production of cytokines, especially in prevision of all the possible therapies to be adopted to allow an active and healthy aging.
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- 2017
47. High fat mass, low muscle mass, and arterial stiffness in a population of free-living healthy subjects
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Giorgio Napolitano, Francesco Cipollone, Andrea Di Blasio, Angelo Di Iorio, P. Ripari, and Roberto Paganelli
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Cross-sectional study ,Population ,Frailty syndrome ,General Medicine ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Blood pressure ,030220 oncology & carcinogenesis ,Internal medicine ,Arterial stiffness ,Lean body mass ,Cardiology ,Medicine ,030212 general & internal medicine ,Sample collection ,business ,education ,Body mass index - Abstract
Introduction A progressive decline in lean body mass and increase in fat mass occur with aging, and result in progressive weakness and impaired mobility; these features are altogether landmarks of the ageing frailty syndrome. High-fat mass and low muscle mass are both associated with an increased risk of cardiovascular events and are supposed to be risk factors for arterial stiffness. Little data analyzing the relationship between body composition and cardio-ankle vascular index (CAVI) are currently available. The main objective of this study was to verify whether low muscle mass and/or high fat mass could be associated with arterial stiffness measured by CAVI. Methods Data are from the cross-sectional assessment of the "Al passo con la tua salute", a clinical study aimed to promote physical function among free-living elderly subjects.After a screening interview and a clinical visit aimed to exclude ineligible persons, 52 volunteers were enrolled in the study. All underwent: clinical examination, physical performance assessment, an interview on lifestyle and dietary habits, and lastly, a blood sample collection after at least 8 hours of fasting. Results CAVI was statistically significantly higher in those participants in the highest tertile of distribution for fat mass compared to all other subjects (P = .03). In those participants in the lowest tertile of distribution of muscle mass, compared to all other, CAVI was also statistically significant higher (P = .01) independently of age, sex, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and systolic blood pressure. Conclusions Low muscle mass and high fat mass were landmarks in the frailty model of aging; therefore, it is not inconsistent that both clinical conditions might share with the "aging vessel" a common pathway, probably mediated through signaling network deregulation and/or through alteration of the balance between energy availability and energy demand.
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- 2019
48. Vitamin D3 improves the effects of low dose Der p 2 allergoid treatment in Der p 2 sensitized BALB/c mice
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Valentina Amato, Mario Di Gioacchino, Roberto Paganelli, Alessia Lamolinara, Cosmo Rossi, Emanuela Clemente, Alessia Gatta, Sara Cortese, Gianni Mistrello, Claudia Petrarca, and Stefania Zanotta
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0301 basic medicine ,Der p 2 ,Allergy ,T regulatory cells ,medicine.medical_treatment ,Immunology ,Inflammation ,Pharmacology ,Allergoid ,BALB/c ,Airborne allergen ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Oral administration ,medicine ,Immunology and Allergy ,Molecular Biology ,Allergen immunotherapy ,biology ,business.industry ,Research ,Immunotherapy ,biology.organism_classification ,Asthma ,Eosinophils ,030104 developmental biology ,IL-10 ,IgE ,medicine.symptom ,business ,Adjuvant ,Vitamin D3 ,030215 immunology - Abstract
Background Airborne allergens can induce an immunological chronic disease characterized by airway hyper responsiveness and inflammation, mediated by exaggerated Th2 immune response. Allergen-specific immunotherapy (AIT) is effective for treating this condition because it is able to modify its natural course by opposing the underlying pathogenic mechanisms and determining immune suppression, immune deviation and tolerance. The rational for the present study was to investigate the possibility of improving allergoid-based IT in terms of efficacy and safety. Recently, 1α,25-dihydroxyvitamin D3 (VD3), the active metabolite of vitamin D3, was described to be a potent inducer of T regulatory cells and to be a good adjuvant in AIT settings. Methods We investigated whether the co-administration of VD3 could potentiate the effect of AIT even when added to a low dose of chemically-modified monomeric allergoid of Der p 2 (d2-OID), in a Derp p 2 (d2)-sensitized BALB/c mice model. Control groups where treated with sham, VD3 alone or d2-OID only. Results The d2-OID alone was not fully successful, as expected for a low dose. VD3 administration was associated with some valuable, although limited, changes in the immunological parameters in the lung. On the contrary, the VD3 adjuvated allergoid vaccine induced the most prominent reduction of airway eosinophilia and Th2 cytokines and concomitant increase of T regulatory cells and IL-10 in the lung and Der p 2-specific IgG2a in the serum. Conclusions The addition of VD3 to a conventional AIT protocol would allow the reduction of allergoid dose needed and therefore, the production costs. Moreover, beneficial immunomodulatory effects have been achieved by the oral administration which might favour the management of the therapy by the patients and their adherence, possibly enhancing the efficacy of the treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12948-016-0044-1) contains supplementary material, which is available to authorized users.
- Published
- 2016
49. Expression profile of the embryonic markers nanog, OCT-4, SSEA-1, SSEA-4, and frizzled-9 receptor in human periodontal ligament mesenchymal stem cells
- Author
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Raffaella Giancola, Marco Marchisio, Jacopo Pizzicannella, Sergio Caputi, Maurizio Piattelli, Hans-Jörg Bühring, Antonio Nanci, Oriana Trubiani, Roberto Paganelli, and S. Zalzal
- Subjects
Adult ,Homeobox protein NANOG ,Stage-Specific Embryonic Antigens ,Periodontal Ligament ,Physiology ,Rex1 ,Clinical Biochemistry ,Lewis X Antigen ,Cell Separation ,Biology ,Oct-4 ,Receptors, G-Protein-Coupled ,Humans ,Cell Shape ,Cells, Cultured ,Cell Proliferation ,Stem cell transplantation for articular cartilage repair ,Homeodomain Proteins ,Gene Expression Profiling ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Nanog Homeobox Protein ,Cell Biology ,Frizzled Receptors ,Cell biology ,Amniotic epithelial cells ,embryonic structures ,Immunology ,Cytokines ,Stem cell ,Octamer Transcription Factor-3 ,Biomarkers ,Adult stem cell - Abstract
Mesenchymal stem cells (MSCs) are self-renewing cells with the ability to differentiate into various mesodermal-derived tissues. Recently, we have identified in adult human periodontal ligament (PDL) a population of stem cells (PDL-MSCs) with the ability to differentiate into osteoblasts and adipocytes. The aim of the present work was to further characterize this population and the expression profile of its cells. To achieve our objective we have used flow cytometry, magnetic cell sorting, cytokine antibody array, and light and electron microscope immunostaining. Our results show that the PDL-MSCs contain a subpopulation of frizzled-9 (CD349) positive cells expressing a panel of key mesenchymal and embryonic markers including CD10, CD26, CD29, CD44, CD73, CD90, CD105, CD166, SSEA-1, and SSEA-4. They are additionally positive for nanog and Oct-4; two critical transcription factors directing self-renewal and pluripotency of embryonic stem cells, and they also express the cytokines EGF and IP-10. The presence of nanog, Oct-4, SSEA-1, and SSEA-4 suggests that PDL-MSCs are less differentiated than bone marrow-derived MSCs. Taken together, these data indicate the presence of immature MSCs in PDL and suggest that the frizzled-9/Wnt pathway plays an important role in regulating proliferation and differentiation of these cells.
- Published
- 2010
50. Airways Remodelling In Children With Controlled Mild-moderate Asthma Correlates With Higher Serum Il-4 But Not With Clinical Score
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Roberto Paganelli, Anna Cingolani, Marika D'Urbano, Francesco Chiarelli, and Sabrina Di Pillo
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medicine.medical_specialty ,business.industry ,Internal medicine ,Moderate asthma ,Immunology ,Immunology and Allergy ,Medicine ,business ,Gastroenterology ,Interleukin 4 - Published
- 2018
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