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Human NK cells: surface receptors, inhibitory checkpoints, and translational applications

Cellular & Molecular Immunology 2019年第5期16卷 430-441页

作者： Simona Sivori Paola Vacca Genny del Zotto Enrico Munari maria Cristina Mingari Lorenzo Moretta Department of Experimental Medicine(DIMES)and Centre of Excellence for Biomedical Research(CEBR) University of GenoaGenoaItaly Department of Immunology IRCCS Bambino GesuChildren’s HospitalRomeItaly Department of Research and Diagnostics Istituto G.GasliniGenoaItaly Department of Diagnostics and Public Health University of VeronaVeronaItaly Department of Pathology Sacro Cuore Don CalabriaNegrarVRItaly UOC Immunologia IRCCS Ospedale Policlinico San Martino GenovaGenoaItaly

NK cells play important roles in innate defenses against viruses and in the control of tumor growth and *** regulation/induction of NK cell function is mediated by an array of activating or inhibitory surface *** humans,major activating receptors involved in target cell killing are the natural cytotoxicity receptors(NCRs)and *** receptors recognize ligands that are overexpressed or expressed de novo upon cell stress,viral infection,or tumor *** HLA-class I-specific inhibitory receptors,including KIRs recognizing HLA-class I allotypic determinants and CD94/NKG2A recognizing the class-Ib HLA-E,constitute a fail-safe mechanism to avoid unwanted NK-mediated damage to healthy *** receptors such as PD-1,primarily expressed by activated T lymphocytes,are important inhibitory checkpoints of immune responses that ensure T-cell ***-1 also may be expressed by NK cells in cancer *** PD-1 ligand(PD-L1)may be expressed by different tumors,PD-1/PD-L1 interactions inactivate both T and NK ***,the reliable evaluation of PD-L1 expression in tumors has become a major issue to select patients who may benefit from therapy with mAbs disrupting PD-1/PD-L1 ***,NKG2A was revealed to be an important checkpoint controlling both NK and T-cell *** most tumors express HLA-E,mAbs targeting NKG2A has been used alone or in combination with other therapeutic mAbs targeting PD-1 or tumor antigens(e.g.,EGFR),with encouraging *** translational value of NK cells and their receptors is evidenced by the extraordinary therapeutic success of haploidentical HSCT to cure otherwise fatal high-risk leukemias.

关键词： Human NK cells NK receptors Inhibitory checkpoints Immunotherapy

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Low-dose tenofovir is more potent than adefovir and is effective in controlling HBV viremia in chronic HBeAg-negative hepatitis B

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World Journal of Gastroenterology 2007年第30期13卷 4096-4099页

作者： Paolo del Poggio Maurizio Zaccanelli maria Oggionni Silvia Colombo Carlo Jamoletti Vesna Puhalo Hepatology Unit Treviglio Hospital (Bg) Italy Blood Bank (Molecular Biology Section) Treviglio Hospital (Bg) Italy

AIM: To study the efficacy of tenofovir disoproxil fumarate (TDF) at low dose in a small open trial of chronic hepatitis B patients with advanced stage disease. METHODS: Eleven patients were treated with TDF 75 mg for a median period of 80 (range, 24-576) wk and then 7 cases were shifted to an adefovir 10 mg treatment group. All patients had been pre-treated with lamivudine: 5 had YMDD resistant mutants and 6 wild- type virus. When TDF was started, 4 patients had low- level viremia and 6 were PCR-negative. RESULTS: During TDF treatment, PCR remained negative in 10 patients, transaminase levels were normal and no significant viral breakthrough was observed. The drug was well tolerated in all cases. When TDF 75 mg was substituted with adefovir 10 mg, 3 out of 7 patients had a persistent viral rebound (2700-130 000 copies/mL), in whom lamivudine had to be reintroduced. CONCLUSION: Low-dose TDF monotherapy can control HBV viremia for an extended period of time without the emergence of resistance and is more potent than adefovir at the standard dosage. The use of a reduced dose of TDF could diminish the cost of therapy in low-income countries, but further studies in a larger population and in HBeAg-positive subjects are needed.

关键词： Tenofovir Chronic Hepatitis B Adefovir Nucleotide analogues Low-income countries

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Genetic susceptibility to Candida infection： a new look at an old entity

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Chinese Medical Journal 2013年第2期126卷 378-381页

作者： Davide Firinu maria Pisanu Bruno Piras Raffaella Meleddu maria Maddalena Lorrai Paolo Emilio Manconi Stefano R. del Giacco Department of Medical Sciences "M. Aresu" Unit of InternalMedicine Allergy and Clinical Immunology University ofCagliari Cagliari Italy

The identification of the first molecular defect leading to Mendelian Susceptibility to Mycobacterial Disease ;MD）,1 a rare syndrome conferring predisposition to（MSMD）,1 a rare syndrome conferring predisposition to disease caused by weakly virulent mycobacteria （such as Mycobacterium bovis, Bacille Calmette Gu6rin vaccines and environmental mycobacteria）, has led to a paradigm shift in the field of primary immunodeficiencies in the last two decades. The ＂classic＂ patient with multiple immunologic abnormalities, conferring a broad susceptibility to multiple and recurrent infectious diseases caused by both weakly pathogenic and more virulent microorganisms, was the main Primary Immunodeficiency （PID） phenotype identified. Since 1996, mutations causing MSMD have been found in at least 6 genes related to interferon （IFN）-7-mediated immunity.2

关键词： chronic mucocutaneous candidiasis Candida infection immunodeficiency autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy," autoimmune polyendoerine syndrome type 1 Th l 7

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Exercise-induced anaphylaxis with an Ayurvedic drug as cofactor:A case report

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World Journal of Clinical Cases 2019年第5期7卷 623-627页

作者： Francesca Losa Margherita Deidda Davide Firinu maria Luisa Di Martino maria Pina Barca Stefano del Giacco Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology University Hospital "Duilio Casula" University of Cagliari

BACKGROUND The practice of Indian Ayurvedic medicine is spreading in Western countries and Shilajit is one of the most used drugs, for its antioxidant activities and immunomodulatory effects. Albeit Shilajit has showed a high degree of safety, it can act as cofactor of anaphylaxis, especially in condition at high risk, such as mast cell activation syndrome(MCAS). We reported this case to sensitize practitioners to investigate to the use of complementary and alternative medicine,in case of exercise-induced anaphylaxis(EIAn).CASE SUMMARY A 43-year-old woman, working as a dance teacher, developed urticaria after ingestion of rice, tuna and Shilajit, which did not respond to intramuscular corticosteroids. Subsequently, she developed dyspnoea and hypotension with loss of consciousness that arose 1 h after sexual activity. The patient did not refer personal history of atopy. Specific IgE for main food allergens resulted negative,with total IgE levels of 14 IU/L. Oral provocation test with Shilajit was not perfomed because the patient refused, but we performed prick-by-prick and patch test that resulted negative. Serum tryptase at the time of anaphylaxis was 20.6 μg/L that fell down to of 10.6 μg/L after therapy, but has remained at the high value after two days and during the follow-up. We performed an analysis of the c-KIT gene in peripheral blood, which was negative. We felt the diagnosis consistent with EIAn in a patient with a possible *** In Western countries the use of drugs from Ayurvedic medicine is more common than in the past. These substances can be cofactors of anaphylaxis in patients with risk factors.

关键词： Indian Ayurvedic medicine Anaphylaxis Exercise-induced anaphylaxis Mast cell activation syndrome Case report

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Modern approach to the clinical management of non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第26期20卷 8341-8350页

作者： maria del Ben Licia Polimeni Francesco Baratta Daniele Pastori Lorenzo Loffredo Francesco Angelico Department of Internal Medicine and Medical Specialities Department of Public Health and Infectious Diseases Sapienza University

Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D3. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Insulin resistance Oxidative stress Cardiovascular risk Statins Vitamin D Vitamin E Pioglitazone

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Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer

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World Journal of Gastrointestinal Oncology 2019年第2期11卷 117-138页

作者： Anna maria Berghella Anna Aureli Angelica Canossi Tiziana del Beato Alessia Colanardi Patrizia Pellegrini Istituto di Farmacologia Traslazionale Consiglio Nazionale delle Ricerche

BACKGROUND Identifying biomarkers for the risk of developing degenerative processes linked to aging and colorectal cancer(CRC) onset that could improve clinical *** To determine valid targets and a predictive biomarker's system of chronicization of inflammation for cancer *** A group of 147 CRC patients was studied. Clinical diagnosis was confirmed histopathologically, and patients were sub-typed using the pathological tumornode-metastasis classification. Thirteen colon adenoma patients and 219 healthy subjects were also studied. A system biology study on Thioredoxin1/CD30 redox-immune systems(Trx1/CD30), T helper cytokines and polymorphisms of killer immunoglobulin-like receptors, FcγRIIa-131 H/R and FcγRIIIa-158 V/F was carried out. Enzyme-linked immunosorbent assay was performed to analyze *** study was executed by polymerase chain reaction sequence-specific primers and sequence-based typing method. Statistical analysis was performed by using the "Statgraphics software systems".RESULTS We found a positive increase between Trx1/RTrx1 levels and sCD30 level and increased age. With respect to the gender relationships, there were distinct differences. Females showed a primary relationship between transforming growth factor beta(TGFβ) with Trx1, whereas males had one with TGFβ and RTrx1. Trx1/CD30 controls the redox immune homeostasis, and an imbalance in the relationship between the Trx1/RTrx1 and sCD30 levels is linked to the onset and progression of tumor. This event happens through different gender-specific cytokine pathways. Our study demonstrated that the serum levels ofTrx1/RTrx1, TGFβ/interleukin(IL)6 and TGFβ/IL4 combinations and the sCD30,IFNγ and IL2 combination constitute a predictive gender specific biomarker system. This is relevant for clinical screening to detect the risk of the potential development or progression of a *** Oxidative stress on Trx1/CD30 is a trigger of cancer disease, and the selected oxid

关键词： Aging and cancer biomarker Cancer personalized treatments Oxidation and immune biomarkers Trx1/CD30 target KIRs and FcγR polymorphisms Th cytokines Aging and disease Cancer-related mechanisms

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Mathematical Model to Elaborate the Table of Thermodynamic Properties

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Journal of Applied Mathematics and Physics 2022年第6期10卷 1951-1967页

作者： Debrayan Bravo Hidalgo Liliana del Carmen Morillo Acosta Nancy del rocio Flores Hinojosa Sharing Knowledge Group (SKG) Quito Ecuador Administrative Sciences Department Universidad Central del Ecuador Quito Ecuador

Purpose: The aim of this scientific contribution is to show the potential that integral calculus has offered to the analysis of thermodynamic processes. Method: Application of Integral Calculus. In this context, the document covers the theoretical principles of integral calculus, such as Theoretical framework and background, Geometric interpretation of the primitive, Primitive existence theorem. Results: Integral calculus and generalized thermodynamic models, and their applications in various thermodynamic analysis contacts such as the Generalized Enthalpy Model, the Generalized Entropy Model, and the Generalized Model applied to gas mixtures and the General Model to elaborate the properties table. Conclusion: The mathematical analysis developed in this document is very useful in engineering and applied physics environments, a fact that supports its common pedagogical practice in university institutions.

关键词： Equations Curves of Thermal Processes Thermodynamic Laws Physics-Mathematics Energy

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Hyperkalemia in Patients on Peritoneal Dialysis: Clinical Use Experience with New Potassium-Binders

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Open Journal of Nephrology 2024年第3期14卷 324-333页

作者： Gennaro Argentino Mario Iorio Alessandra Antonia Mele Andrea Camocardi Enrica Emanuela Cascone maria Elena Liberti Adelia Sagliocca Andrea Pota Luigi Russo maria Luisa Sirico Germano Terzini Michele Cavasso Chiara Mennillo Francesca Nettuno Raffaele Genualdo Giuseppe Surfaro Lucia Di Micco UOC Nefrologia e Dialisi Ospedale del Mare Naples Italy UOC Chirurgia Generale Ospedale del Mare Naples Italy

Background: Patients with end-stage kidney disease (ESKD) on maintenance dialysis have a high risk of developing hyperkalemia. In addition to traditional approaches, a new option for the management of patients on dialysis includes the use of a potassium binder, sodium zirconium cyclosilicate (SZC). We evaluated the effect and safety of SZC in patients with chronic PD. Objective: To present a case series that illustrates the real-world use of new potassium-binders in hyperkalemic patients on peritoneal dialysis. Methods: This case series collected 9 patients on PD with baseline potassium values > 5.5 mmol/l and who were treated with SZC 5 g once a day. Data were collected at baseline and at 1, 2, and 3 months after initiation of treatment. Results: The median age of patients was 64.5 years and the median duration of observation was 90 ± 5 days. It was observed that median serum potassium decreased (5.8 mmol/l at baseline with a range of 5.8 mmol/L - 6.8 mmol/L versus 4.5 in the third month with a range of 3.6 mmol/L - 5.3 mmol/L) after SZC treatment. Adverse events were observed in 2 (22.2%). The unique adverse event was constipation and presented in 2 patients (22.2%). Constipation was mild and transient during the observation period. No adverse events of special interest were reported. Conclusion: Normokalemia was established and maintained in this series of patients treated with SZC. No episodes of hyper- or hypo-kalemia were observed. SCZ had a good safety profile and was well tolerated over 3 months.

关键词： SZC Sodium Zirconium Cyclosilicate Hyperkalaemia Peritoneal Dialysis

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Gut microbiota and COVID-19: An intriguing pediatric perspective

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World Journal of Clinical Cases 2022年第23期10卷 8076-8087页

作者： maria Sole Valentino Claudia Esposito Simone Colosimo Angela maria Caprio Simona Puzone StefanoGuarino Pierluigi Marzuillo Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Childand General and Specialized SurgeryUniversity of Campania Luigi VanvitelliNaples 80138Italy

Gastrointestinal(GI)involvement has been reported in approximately 50%of patients with coronavirus disease 2019(COVID-19),which is due to the pathogenic role of inflammation and the intestinal function of the angiotensinconverting enzyme 2 and its *** adult data has pointed out that gut dysbiosis might occur in these patients with a potential impact on the severity of the disease,however the role of gut microbiota in susceptibility and severity of COVID-19 disease in children is still poorly *** the last decades,the crosstalk between gut and lung has been largely recognized resulting in the concept of“gut-lung axis”as a central player in modulating the development of several *** organs are involved in the common mucosal immune system(including bronchus-associated and gut-associated lymphoid tissues)and their homeostasis is crucial for human *** this framework,it has been found that the role of GI dysbiosis is affecting the homeostasis of the gutliver *** note,a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects,but it remains to be *** on the increased risk of inflammatory diseases in children with COVID-19,the potential correlation between gut microbiota dysfunction and COVID-19 needs to be studied in this *** aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.

关键词： Gut Microbiota Dysbiosis Microbiome COVID-19 Children

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Measurement of β-1,3 Glucanase Activity in Permeabilized Discs of Leaves of Healthy and Scald-Diseased Plants

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Journal of Life Sciences 2012年第2期6卷 175-181页

作者： rocio Santiago Ana-maria Millanes maria-Estrella Legaz Carlos Vicente Department of Plant Physiology Faculty of Biology Complutense University Madrid 28040 Spain Department of Biology and Geology School of Science and Technology King Juan Carlos University Madrid 28040 Spain

Leaf discs of five cultivars of sugarcane exhibiting different degree of susceptibility to leaf scald were used to measure β-1,3 glucanase activity before and after experimental infection with Xanthomonas albilineans. Leaf discs were permeabilized with iso-propanol to facilitate the uptake of the enzyme substrate by intact tissues and to improve the enzyme assay. Bacterial infection significantly enhances β-1,3 glucanase activity of sensitive cultivars whereas significantly decreased that of the resistant one. Low concentrations of salicylate increase the hydrolase activity whereas jasmonic acid do not act as an elicitor of the enzyme and β-1,3 glucanase, such as laminarin, significantly inhibits the production of β-1,3 glucanase. Thus, the enzyme must be considered as a sensitivity factor induced by the pathogen.

关键词： Elicitors β-1 3 glucanase leaf scald salicylate jasmonic sugarcane.

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