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Pediatric nonalcoholic fatty liver disease,metabolic syndrome and cardiovascular risk

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World Journal of Gastroenterology 2011年第26期17卷 3082-3091页

作者： Lucia Pacifico Valerio Nobili Caterina Anania paola Verdecchia Claudio Chiesa Department of Pediatrics Sapienza University of Rome Department of Hepato-gastroenterology and Nutrition Pediatric Hospital "Bambino Gesù" Institute of Translational Pharmacology National Research Council

Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol *** mildest form is simple steatosis in which triglycerides accumulate within hepatocytes.A more advanced form of NAFLD,nonalcoholic steatohepatitis,includes inflammation and liver cell injury,progressive to cryptogenic *** has become the most common cause of chronic liver disease in children and *** recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic *** is strongly associated with abdominal obesity,type 2 diabetes,and dyslipidemia,and most patients have evidence of insulin ***,NAFLD shares many features of the metabolic syndrome(MetS),a highly atherogenic condition,and this has stimulated interest in the possible role of NAFLD in the development of *** evidence suggests thatNAFLD is associated with a significantly greater overall mortality than in the general population,as well as with increased prevalence of cardiovascular disease(CVD),independently of classical atherosclerotic risk ***,several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and ***,the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular *** children,the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established *** goals for NAFLD should address nutrition,physical activity,and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

关键词： Nonalcoholic fatty liver disease Metabolicsyndrome Cardiovascular risk Children

The translational revolution in atopic dermatitis:the paradigm shift from pathogenesis to treatment

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Cellular & Molecular Immunology 2023年第5期20卷 448-474页

作者： paola Facheris Jane Jeffery Ester Del Duca Emma Guttman-Yassky Laboratory of Inflammatory Skin Diseases Department of DermatologyIcahn School of Medicine at Mount SinaiNew YorkNYUSA Humanitas Clinical and Research Center Department of DermatologyRozzanoMilanoItaly Duke University School of Medicine DurhamNCUSA Department of Dermatology Icahn School of Medicine at Mount SinaiNew YorkNYUSA.

Atopic dermatitis(AD)is the most common inflammatory skin disease,and it is considered a complex and heterogeneous *** phenotypes of AD,defined according to the patient age at onset,race,and ethnic background;disease duration;and other disease characteristics,have been recently described,underlying the need for a personalized treatment *** advancements in understanding AD pathogenesis resulted in a real translational revolution and led to the exponential expansion of the therapeutic *** study of biomarkers in clinical studies of emerging treatments is helping clarify the role of each cytokine and immune pathway in AD and will allow addressing the unique immune fingerprints of each AD *** medicine will be the ultimate goal of this targeted translational *** this review,we discuss the changes in the concepts of both the pathogenesis of and treatment approach to AD,highlight the scientific rationale behind each targeted treatment and report the most recent clinical efficacy data.

关键词： Atopic dermatitis translational revolution biomarkers eczema

Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent

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World Journal of Gastroenterology 2006年第14期12卷 2187-2194页

作者： Nicola Dioguardi Fabio Grizzi Barbara Franceschini paola Bossi Carlo Russo Laboratori di Medicina Quantitativa Istituto Clinico Humanitas IRCCS RozzanoMilanand "Michele Rodriguez" FoundationInstitute for Quantitative Methods in MedicineMilanItaly Department of Pathology Istituto Clinico Humanitas IRCCS RozzanoMilanItaly

AIM： To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen. METHODS： Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computeraided method based on the international system meter rectified using fractal principles. RESULTS： The following were described： geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the ＂staging＂ of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value; the quantitative liver tissue architectural changes with the Hurst exponent. CONCLUSION： Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue. The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

关键词： Liver Fibrosis Cirrhosis Staging Image analysis Fractals

L-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes

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Protein & Cell 2018年第4期9卷 322-332页

作者： Cecile Apert paola Romagnoli Joost P, M. van Meerwijk CPTP Universite de Toulouse CNRS Inserm UPS Toulouse France

Immunosuppressive regulatory T lymphocytes （Treg） expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 （IL-2） and IL-15. The more recently appreciated involvement of TGF-β in thymic Treg development is also briefly discussed. Finally, we discuss how cytokine-dependence of Treg development allows for temporal, quantitative, and potentially qualitative modulation of this process.

关键词： regulatory T cells thymus differentiation,IL-2 IL-15

Tumor-associated myeloid cells:diversity and therapeutic targeting

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Cellular & Molecular Immunology 2021年第3期18卷 566-578页

作者： Alberto Mantovani Federica Marchesi Sebastien Jaillon Cecilia Garlanda paola Allavena Department of Immunology and Inflammation Humanitas Clinical and Research Center-IRCCSRozzanoItaly Department of Biomedical Science Humanitas UniversityRozzanoItaly The William Harvey Research Institute Queen Mary University of LondonLondonUK Department of Biotechnology and Translational Medicine University of MilanMilanItaly

Myeloid cells in tumor tissues constitute a dynamic immune population characterized by a non-uniform phenotype and diverse functional *** tumor-associated macrophages(TAMs),which are more abundantly represented,and tumor-associated neutrophils(TANs)are known to sustain tumor cell growth and invasion,support neoangiogenesis and suppress anticancer adaptive immune *** recent decades,several therapeutic approaches have been implemented in preclinical cancer models to neutralize the tumor-promoting roles of both TAMs and *** of the most successful strategies have now reached the clinic and are being investigated in clinical *** this review,we provide an overview of the recent literature on the evergrowing complexity of the biology of TAMs and TANs and the development of the most promising approaches to target these populations therapeutically in cancer patients.

关键词： tumor-associated macrophages tumor microenvironment macrophage targeting

Immortalized hippocampal astrocytes from 3xTg-AD mice,a new model to study disease-related astrocytic dysfunction:a comparative review

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Neural Regeneration Research 2023年第8期18卷 1672-1678页

作者： Laura Tapella Giulia Dematteis Armando A Genazzani Massimiliano De paola Dmitry Lim Department of Pharmaceutical Sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly Department of Neuroscience Mario Negri Institute for Pharmacological Research IRCCSMilanoItaly

Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific ***,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific ***,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including *** models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and ***-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in ***,no stable cell lines were available from genetic mouse AD ***,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary *** groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier *** we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived *** conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.

关键词： Alzheimer's disease astrocytes immortalization astroglial Alzheimers's disease model blood-brain barrier calcium signaling central nervous system homeostasis disproteostasis endoplasmic reticulum-mitochondria contacts induced pluripotent stem cell-derived astrocytes protein synthesis

Methodology and evidence from a case study in Rome to increase pedestrian safety along home-to-school routes

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Journal of Traffic and Transportation Engineering(English Edition) 2020年第5期7卷 715-727页

作者： Maria Vittoria Corazza Daniela D'Alessandro paola Di Mascio Laura Moretti Department of Civil Building and Environmental EngineeringSapienza University of RomeRome 00185Italy

Home-to-school routes are very sensitive areas: they represent, for children, a learning tool for their everyday activities, but if poorly designed, maintained and equipped they can expose them to traffic risks. Sidewalks' inappropriate level of service and poor maintenance, especially, are main factors contributing to walking unsuitability, thus to poor comfort and safety levels for young pedestrians, and more in general for all the vulnerable non-motorized road users. This paper deals with a methodology specifically developed to highlight the quality of the urban environment where the home-to-school routes are located, according to four main criteria: wellbeing, usage, appearance, and safety and security. Each criterion is associated with a checklist including the most relevant features to assess, with a focus on maintenance as a key parameter to create safe and comfortable routes to school. An application, a case study in Rome, where the lack of regular maintenance results into a network of unsafe sidewalks, is also presented, analyzing three different areas where a number of schools are located. Detours when approaching school premises were surveyed, due to the levels of distresses and linked to the poor comfort and safety levels. As the mutual influence of built environment over road safety and maintenance requirements for home-to-school paths is not largely investigated thus far, the paper's goal is to provide advanced knowledge for studies and applications further afield.

关键词： Traffic engineering Road safety Pedestrians Home-to-school routes Sidewalks

Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors

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World Journal of Pediatrics 2019年第5期15卷 465-470页

作者： paola Muggeo Vito Michele Rosario Muggeo paola Giordano Maurizio Delvecchio Maria Altomare Chiara Novielli Marco Matteo Ciccone Gabriele D'Amato Maria Felicia Faienza Nicola Santoro Department of Pediatric Oncology and Hematology University Hospital of PoliclinicoPiazza G.Cesare 1170124 BariItaly Department of Economical Business and Statistical SciencesUniversity of PalermoPalermoItaly Department of Biomedicine and Human Oncology Pediatric SectionUniversity"A.Moro"BariItaly Pediatric and Neonatology Unit Mother and Children Health Care Department"Madonna delle Grazie"HospitalASL MateraMateraItaly Cardiovascular Diseases Section Department of Emergency and Organ TransplantationUniversity"A.Moro"BariItaly Neonatal Intensive Care Unit Di Venere HospitalBariItaly

Background Vitamin D(25-OHD)has a role in bone health after treatment for cancer.25-OHD deficiency has been associated with risk factors for cardiovascular disease,but no data focusing on this topic in childhood cancer survivors have been *** investigated the 25-OHD status in children treated for acute lymphoblastic leukemia(ALL),and evaluated its influence on vascular *** 25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy *** were grouped according to 25-OHD level(<20 ng/m or≥20 ng/ml).Auxological parameters,biochemical and hemostatic markers of endothelial function(AD,HMW-AD,ET-1,vWFAg,TAT,D-dimers,Fbg,and hs-CRP),ultrasound markers of vascular endothelial function(flow-mediated dilatation,FMD,common carotid intima-media thickness,C-IMT,and antero-posterior diameter of infra-renal abdominal aorta,APAO)were evaluated in the *** Cases showed higher prevalence of 25-OHD deficiency than controls(p=0.002).In univariate analysis via mean comparisons,25-OHD deficient(<20 ng/ml)patients showed higher C-IMT values compared to the 25-OHD non-deficient(≥20 ng/ml)group(P=0.023).Significant differences were also found for ET-1(P=0.035)and AD-HMW(P=0.015).In the multiple regression models controlling for some confounders,25-OHD still was associated with C-IMT(P=0.0163),ET-1(P=0.0077),and AD-HMW(P=0.0008).Conclusions Childhood ALL survivors show higher prevalence of 25-OHD deficiency as compared to *** 25-OHD levels appear to be linked to indicators of endothelial and vascular *** monitoring of 25-OHD balance may help to prevent cardiovascular diseases in childhood ALL survivors,characterized by high cardiovascular risk.

关键词： Acute lymphoblastic leukemia Cardiovascular disease C-IMT Vascular ultrasound studies Vitamin D

Antiseptic Efficacy of A Soap Made from Biosurfactants Isolated from Bacillus and Lactobacillus against Pathogenic Bacteria

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Advances in Microbiology 2024年第1期14卷 31-58页

作者： Frédéric Yannick Okouakoua Christian Aimé Kayath Nicaise Saturnin Mokémiabeka Varelle Bervanie Ngala Elenga Digne Nedjea N’goma-Mona Ndelani Nkalla Lambi Sandra paola Elenga Wilson Christ Dieuveil Bayakissa Malanda Rodinet Tsana Junior Patrick Sergy Bissoko1 Moïse Doria Kaya-Ongoto Duchel Jeanedvi Kinavouidi Etienne Nguimbi Laboratoire de Biologie Cellulaire et Molé culaire (BCM) Facult&eacute des Sciences et Techniques Universit&eacute Marien N’gouabi Brazzaville Congo Institut National de Recherche en Sciences Exactes et Naturelles (IRSEN) Avenue de l’Auberge Gascogne Brazzaville Congo

The aim of our study was to use a biosurfactant produced by Bacillus and Lactobacillus isolates as an antiseptic in the formulation of local soap. A total of 60 isolates were characterized by microbiological techniques (30 Bacillus and 30 Lactobacillus) and the ability to produce biosurfactants was demonstrated by a hydrocarbon emulsification index (E24). The emulsification indexes (E24) varied from 9% to 100% for Bacillus and from 33% to 100% for Lactobacillus as well. The antagonistic assay showed that biosurfactants were able to inhibit the formation of biofilms and growth of pathogens such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, Salmonella typhirium, Shigella boydii and Proteus mirabilis. The biosurfactant consortium (BioC) from Bacillus consortium and from Lactobacillus was able to inhibit biofilm formation and the pathogens growth. The BioC was stable to alkaline pH and the temperatures stability of Biosurfactant was ranging from 50°C to 90°C. The soap was made by the cold saponification process using one biosurfactant consortium formulated. This soap has a pH of 10 and showed good cleaning power and good foam stability. Similarly, the soap showed good antiseptic power and disinfection power against all pathogens tested. Handwashing is critical to preventing disease transmission. The persistence of pathogens in waste water was evaluated. The BioS produced showed good disinfection power against all pathogens tested. The valor of reduction on the hands and in the waste water was significantly more than compared to the control soaps used. This soap could be used in the prevention, fighting, and treatment of bacterial and viral infections.

关键词： Antiseptic Soap Biosurfactants Bacillus Lactobacillus Disinfection Pathogens bacteria