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Specific contribution of mannose-binding lectin murine isoforms to brain ischemia/reperfusion injury

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Cellular & Molecular Immunology 2020年第3期17卷 218-226页

作者： Laura Neglia Marco Oggioni Domenico Mercurio Maria-Grazia De Simoni Stefano Fumagalli1 istituto di Ricerche Farmacologiche Mario Negri IRCCS Department of NeuroscienceMilanItaly

Mannose-binding lectin(MBL),an initiator of the lectin pathway(LP)of complement activation,is detrimental in ischemic stroke,as shown in clinical studies and rodent *** humans have one functional MBL protein,rodents have two isoforms,MBL-A and MBL-C,whose functions relative to that of human MBL are *** permit the clinical translation of preclinical data,we aimed to define the specific contributions of MBL-A and MBL-C to brain *** subjected mice with double(MBL^(−/−))or single(MBL-A^(−/−)or MBL-C^(−/−))MBL isoform depletion to transient middle cerebral artery occlusion(tMCAo).MBL^(−/−) mice had fewer neurological deficits and smaller ischemic lesions than WT ***-A^(−/−) mice had smaller lesions than WT mice and exhibited no significant behavioral defects,whereas MBL-C^(−/−) mice did not differ from WT *** induction of Mbl1 and Mbl2(the MBL-A and MBL-C genes)expression 48 h after tMCAo was similar across *** time course of Mbl1 and Mbl2 expression in WT ischemic mice showed that Mbl1 activation occurred earlier(24 h)than Mbl2 activation(48 h).The plasma levels of MBL-A and MBL-C in MBL-C^(−/−) and MBL-A^(−/−) mice,respectively,were similar to those in WT mice both at baseline and at 48 h after *** 48 h,MBL-A^(−/−)ischemic mice showed higher MBL-C levels in the brain than WT *** and MBL-C^(−/−) ischemic mice had higher LP activity in plasma and,accordingly,higher levels of C3 deposition in the brain than MBL-A^(−/−) and MBL^(−/−) *** conclusion,mice with depletion of both MBL isoforms exhibited strong protection from ischemia/reperfusion ***-A was the main contributor to injury,likely owing to its earlier activation after ischemia and more efficient activation of the complement system than MBL-C.

关键词： injury depletion likely

Intestinal microbiota in inflammatory bowel disease:Friend of foe?

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World Journal of Gastroenterology 2011年第5期17卷 557-566页

作者： Francesca Fava Silvio Danese Inflammatory Bowel Disease Unit Istituto Clinico HumanitasVia Manzoni 11320089 RozzanoMilanoItaly

Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.

关键词： Microbiota Inflammatory bowel disease Microbial dysbiosis Immune tolerance Innate immu-nity Mucosal barrier

Anxiety,depression,and quality of life in Parkinson's disease:the implications of multidisciplinary treatment

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Neural Regeneration Research 2021年第3期16卷 587-590页

作者： Viviana Lo Buono Rosanna Palmeri Simona De Salvo Matteo Berenati Agata Greco Rosella Ciurleo Chiara Sorbera Vincenzo Cimino Francesco Corallo Placido Bramanti Silvia Marino Giuseppe Di Lorenzo Lilla Bonanno Department of Neurobioimaging Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Centro Neurolesi Bonino-PulejoMessinaItaly

Anxiety and depression in Parkinson's disease(PD)reduce well-being of the *** alterations influence motor skills and cognitive performance;moreover,they contribute significantly and independently to worsen rehabilitative treatment *** investigated anxiety,depression,and quality of life in PD patients subjected to multidisciplinary rehabilitative *** self-controlled study included 100 PD patients(49 males and 51 females with the mean age of 64.66 years)admitted to 60 days hospitalization rehabilitative program,between January 2017 and December ***,cognitive,linguistic abilities,and functional independence were evaluated at admission(T0 baseline visit)and 60 days after(T1)the multidisciplinary rehabilitation including motor exercises,speech therapies,and cognitive *** multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood,motor abilities,autonomy in the activities of daily life,perception of quality of life,cognitive performance and speech ***-motor symptoms may worsen severe disability and reduce quality of *** are often poorly recognized and inadequately ***,multidisciplinary rehabilitative training represents an optimal strategy to improve disease *** study was approved by Istituito di Ricovero e Cura a Carattere Scientifico(IRCCS)Centro Neurolesi"Bonino-Pulejo"Ethical Committee(approval No.6/2016)in June 2016.

关键词： anxiety depression multidisciplinary rehabilitation Parkinson's disease

CHK2 kinase in the DNA damage response and beyond

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Journal of Molecular Cell Biology 2014年第6期8卷 442-457页

作者： Laura Zannini Domenico Delia Giacomo Buscemi Department of Experimental Oncology Fondazione IRCCS Istituto Nazionale dei Tumori Via Amadeo 42 20133 Milan Italy

The serine/threonine kinase CHK2 is a keycomponent of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates 〉20 proteins to induce the appropriate cellular response, which, depending on the extent of damage, the cell type, and other factors, could be cell cycle checkpoint activation, induction of apoptosis or senescence, DNA repair, or tolerance of the damage. Recently, CHK2 has also been found to have cellular functions independent of the presence of nuclear DNA lesions. In par- ticular, CHK2 participates in several molecular processes involved in DNA structure modification and cell cycle progression. In this review, we discuss the activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells. These activities are also considered in relation to a possible role of CHK2 in tumorigenesis and, as a consequence, as a target of cancer therapy.

关键词： DNA damage checkpoints apoptosis genomic stability

Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma

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World Journal of Gastroenterology 2007年第21期13卷 2952-2955页

作者： Roberto Miraglia Giada Pietrosi Luigi Maruzzelli Ioannis Petridis Settimo Caruso Gianluca Marrone Giuseppe Mamone Giovanni Vizzini Angelo Luca Bruno Gridelli istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione (IsMeTT).University of Pittsburgh Medical Center Italy

AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS:A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m2,infused over 30 min using a peristaltic pump,and followed by Lipiodol and Gelfoam embolization. RESULTS:Patients characteristics were:mean age,62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size,3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm,n = 51; 2.1-3.0 cm,n = 35; 3.1-4.0 cm,n = 29; 4.1-5.0 cm,n = 22; 5.1-6.0 cm,n = 11; and > 6.0 cm,n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%),massive (90%-99%) necrosis in 16 patients (10%),partial (50%-89%) necrosis in 18 patients (11%) and poor ( 6.0 cm,respectively. Kaplan-Mayer survival at 24-mo was 88%,68%,59%,59%,45%,and 53% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. CONCLUSION:Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm,TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embo

关键词： Transcatheter embolization/chemoembolization Hepatocellular carcinoma

Could autophagy dysregulation link neurotropic viruses to Alzheimer’s disease?

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Neural Regeneration Research 2019年第9期14卷 1503-1506页

作者： Maria Anele Romeo Alberto Faggioni Mara Cirone Department of Experimental Medicine Sapienza University of Rome Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti

Neurotropic herpesviruses have been associated with the onset and progression of Alzheimer’s disease,a common form of dementia that afflicts a large percentage of elderly ***,among the neurotropic herpesviruses,herpes simplex virus-1,human herpesvirus-6A,and human herpesvirus-6B have been reported to infect several cell types present in the central nervous system and to dysregulate autophagy,a process required for homeostasis of cells,especially *** autophagosome accumulation,indicating an unbalance between autophagosome formation and autophagosome degradation,has been observed in neurons of Alzheimer’s disease patients and may play a role in the intracellular and extracellular accumulation of amyloidβand in the altered protein tau ***,herpesvirus infection of central nervous system cells such as glia and microglia can increase the production of oxidant species through the alteration of mitochondrial dynamics and promote inflammation,another hallmark of Alzheimer’s *** evidence suggests that it is worth further investigating the role of neurotropic herpesviruses,particularly human herpesvirus-6A/B,in the etiopathogenesis of Alzheimer’s disease.

关键词： Alzheimer’s disease autophagy HHV-6A HHV-6B HSV-1 neurotropic viruses amyloidβ tau protein reactive oxygen species inflammation AD

Temperature-dependent photoluminescent behavior of millimeter-scale Cs_(4)PbBr_(6)/CsPbBr_(3) bulk crystals and their application to white light-emitting diodes

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Journal of Materials Science & Technology 2024年第12期179卷 57-65页

作者： Qi Wang Sirous Khabbaz Abkenar Matilde Cirignano Hailong Yu Wenzhi Wu Giorgio Divitini School of Electronic Engineering Heilongjiang UniversityHarbin 150030China Electron Spectroscopy and Nanoscopy Istituto Italiano di TecnologiaGenova 16163Italy Dipartimento di Chimica e Chimica Industriale Universitàdegli Studi di GenovaGenova 16146Italy Photonic Nanomaterials Istituto Italiano di TecnologiaGenova 16163Italy

The zero-dimensional perovskite composite Cs_(4)PbBr_(6)/CsPbBr_(3) has attracted significant attention for its remarkable photoluminescence(PL),which remains highly effective even in solid *** work presents a detailed analysis of the steady-state and time-resolved PL(TRPL)behavior of millimeter-scale Cs_(4)PbBr_(6)/CsPbBr_(3) crystals over a temperature range of 80 to 360 K,which covers exciton binding en-ergy,phonon energy,and PL peak energy shifting with increasing *** to the results,Cs_(4)PbBr_(6)/CsPbBr_(3) exhibits high exciton binding energy and phonon energy,with calculated values of 358.7 and 94.8 meV,***,when the temperature is below~235 K,thermal expan-sion dominates to influence the TRPL and peak energy,whereas electron-phonon interaction becomes the dominant factor as temperature rises from 235 to 325 *** is found that Cs_(4)PbBr_(6)/CsPbBr_(3) has a PL behavior similar to CsPbBr_(3),and characterization and TRPL results demonstrate that nanometer-scale CsPbBr_(3) crystals embed in the Cs_(4)PbBr_(6) bulk ***,a white light-emitting diode(WLED)device based on Cs_(4)PbBr_(6)/CsPbBr_(3) with luminous efficiency of 64.56 Im/W is fabricated,and its color coordinate is measured as(0.34,0.31)under 20 mA,which is in close proximity to the standard white color ***,the color gamut of the device is measured as 128.66%of the National Televi-sion Systems Committee(NTSC).The WLED electroluminescence(EL)spectra show high Correlated Color Temperature(CCT)stability for the working current varying from 5 to 100 mA,and after continuous oper-ation for 12 h,the EL intensity decreases and stabilizes at~70%of the initial EL *** findings suggest that Cs_(4)PbBr_(6)/CsPbBr_(3) crystals are a promising candidate for WLEDs.

关键词： Zero-dimensional perovskites Photoluminescence Exciton binding energy White light-emitting diode

The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial-mesenchymal transition, and immune response

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Cancer Communications 2018年第1期38卷 745-758页

作者： Andrea Devecchi Loris De Cecco Matteo Dugo Donata Penso Gianpaolo Dagrada Silvia Brich Silvia Stacchiotti Marialuisa Sensi Silvana Canevari Silvana Pilotti Platform of Integrated Biology Department of Applied Research and Technology DevelopmentFondazione IRCCS Istituto Nazionale dei Tumori di Milano2133 MilanItaly Department of Diagnostic Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale dei Tumori di Milano20133 MilanItaly Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori di Milano20133 MilanItaly

Background:Desmoplastic small round cell tumor(DSRCT)is a rare,aggressive,and poorly investigated simple sarcoma with a low frequency of genetic deregulation other than an Ewing sarcoma RNA binding protein 1(EWSR1)-Wilm’s tumor suppressor(WT1)*** used whole-exome sequencing to interrogate six consecutive pretreated DSRCTs whose gene expression was previously ***:DNA libraries were prepared from formalin-fixed,paraffin-embedded archival tissue specimens following the Agilent SureSelectXT2 target enrichment protocol and sequenced on Illumina NextSeq *** sequence data were aligned to the reference genome with Burrows-Wheeler Aligner *** mutations and copy number alterations(CNAs)were identified using MuTect2 and EXCAVATOR2,*** functions associated with altered genes were investigated through Ingenuity Pathway Analysis(IPA)***:A total of 137 unique somatic mutations were identified:133 mutated genes were case-specific,and 2 were mutated in two cases but in different *** the 135 mutated genes,27%were related to two biological categories:DNA damage-response(DDR)network that was also identified through IPA and mesenchymal-epithelial reverse transition(MErT)/epithelial-mesenchymal transition(EMT)already demonstrated to be relevant in *** mutated genes in the DDR network were involved in various steps of transcription and particularly affected *** of these genes encoded RNA-binding proteins or DNA/RNA-binding proteins,which were recently rec-ognized as a new class of DDR *** in genes/gene families,involved in MErT/EMT and DDR,were recurrent across patients and mostly segregated in the MErT/EMT *** addition,recurrent gains of regions in chromosome 1 involving many MErT/EMT gene families and loss of one arm or the entire chromosome 6 affecting relevant immune-regulatory genes were ***:The emerging picture is an extreme inter-tumor heter

关键词： Desmoplastic small round cell tumor Whole-exome sequencing Somatic mutations Copy number alterations Chromosome imbalance DNA damage response Genomic stability Mesenchymal-epithelial reverse transition/epithelial-mesenchymal transition Immune response

Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

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Chinese Journal of Cancer 2016年第10期35卷 546-559页

作者： Vittoria Disciglio Andrea Devecchi Orazio Palumbo Massimo Carella Donata Penso Massimo Milione Giorgio Valle Marco Alessandro Pierotti Marco Vitellaro Lucio Bertario Silvana Canevari Stefano Signoroni Loris De Cecco Department of Experimental Oncology and Molecular Medicine Func-tional Genomics and BioinformaticsFondazione IRCCS Istituto Nazionale dei Tumori20133 MilanItaly. Medical Genetics Unit IRCCS Casa Sollievo della Soferenza71013 San Giovanni Rotondo FGItaly. Department of Pathol-ogy and Laboratory Medicine Fondazione IRCCS Istituto Nazionale Tumori20133 MilanItaly. Department of Biology University of Padova35131 PaduaItaly. Fondazione IRCCS istituto Nazionale dei Tumori 20133 MilanItaly. Hereditary Digestive Tract Tumors Unit Department of Preventive and Pre-dictive MedicineFondazione IRCCS Istituto Nazionale dei Tumori20133 MilanItaly. Colorectal Surgery Unit Department of SurgeryFondazione IRCCS Istituto Nazionale dei Tumori20133 MilanItaly.

Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been *** presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human ***: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

关键词： Androgen insensitivity syndrome Androgen receptor Colorectal cancer Single nucleotide polymorphism array Testosterone Whole exome sequencing