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Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection

Cellular & Molecular Immunology 2023年第10期20卷 1101-1113页

作者： salomés.pinho Inês Alves Joana Gaifem Gabriel A.Rabinovich i3s–Institute for Research and Innovation in Health University of Porto4200-135PortoPortugal ICBAs-school of Medicine and Biomedical sciences University of Porto4050-313PortoPortugal Faculty of Medicine University of Porto4200-319PortoPortugal Laboratorio de Glicomedicina Instituto de Biología y Medicina Experimental(IBYME)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)C1428Ciudad de Buenos AiresArgentina Facultad de Ciencias Exactas y Naturales Universidad de Buenos AiresC1428Ciudad de Buenos AiresArgentina

The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous and exogenous insults.Disruption of these safeguard and homeostatic mechanisms can lead to unpredictable inflammatory and autoimmune responses,whereas deficiency of immune stimulatory pathways may orchestrate immunosuppressive programs that contribute to perpetuate chronic infections,but also influence cancer development and progression.Glycans have emerged as essential components of homeostatic circuits,acting as fine-tuners of immunological responses and potential molecular targets for manipulation of immune tolerance and activation in a wide range of pathologic settings.Cell surface glycans,present in cells,tissues and the extracellular matrix,have been proposed to serve as“self-associated molecular patterns”that store structurally relevant biological data.The responsibility of deciphering this information relies on different families of glycan-binding proteins(including galectins,siglecs and C-type lectins)which,upon recognition of specific carbohydrate structures,can recalibrate the magnitude,nature and fate of immune responses.This process is tightly regulated by the diversity of glycan structures and the establishment of multivalent interactions on cell surface receptors and the extracellular matrix.Here we review the spatiotemporal regulation of selected glycan-modifying processes including mannosylation,complex N-glycan branching,core 2 O-glycan elongation,LacNAc extension,as well as terminal sialylation and fucosylation.Moreover,we illustrate examples that highlight the contribution of these processes to the control of immune responses and their integration with canonical tolerogenic pathways.Finally,we discuss the power of glycans and glycan-binding proteins as a source of immunomodulatory signals that could be leveraged for the treatment of autoimmune inflammation and chronic infection.

关键词： Immune response Inflammation Infection Glycans Glycosylation Glycan-binding proteins

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Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity

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Cellular & Molecular Immunology 2023年第8期20卷 955-968页

作者： Manuel M.Vicente Inês Alves Ângela Fernandes Ana M.Dias Beatriz santos-Pereira Elena Pérez-Anton sofia santos Tao Yang Alexandra Correia Anja Münster-Kühnel Afonso R.M.Almeida sarina Ravens Gabriel A.Rabinovich Manuel Vilanova Ana E.sousa salomés.pinho i3s–Institute for Research and Innovation in Health University of PortoPortoPortugal Institute of Biomedical sciences Abel salazar(ICBAs) University of PortoPortoPortugal Graduate Program in Areas of Basic and Applied Biology(GABBA) ICBASUniversity of PortoPortoPortugal Faculty of Medicine University of PortoPortoPortugal Nephrology Department Centro Hospitalar e Universitário do PortoPortoPortugal Institute of Immunology Hannover Medical SchoolHannoverGermany Institute of Clinical Biochemistry Hannover Medical SchoolHannoverGermany Instituto de Medicina Molecular João Lobo Antunes Faculdade de MedicinaUniversidade de LisboaLisboaPortugal Laboratorio de Inmunopatología Instituto de Biología y Medicina Experimental(IBYME)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Ciudad de Buenos AiresArgentina Laboratorio de Inmuno-oncología Translacional Instituto de Biología y Medicina Experimental(IBYME)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Ciudad de Buenos AiresArgentina Facultad de Ciencias Exactas y Naturales(FCEyN) Universidad de Buenos AiresCiudad de Buenos AiresArgentina

T-cell development ensures the formation of diverse repertoires of T-cell receptors(TCRs)that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells,including T-lymphocytes,that regulates activity/functions.Although these structures are known to be involved in TCR-selection in DP thymocytes,it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease.Here,we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes,as well as dynamic alterations.After restricting the N-glycosylation profile of thymocytes to high-mannose structures,using specific glycoengineered mice(Rag1CreMgat1fl/fl),we showed remarkable defects in key developmental checkpoints,includingß-selection,regulatory T-cell generation andγδT-cell development,associated with increased susceptibility to colon and kidney inflammation and infection.We further demonstrated that a single N-glycan antenna(modeled in Rag1CreMgat2fl/fl mice)is the sine-qua-non condition to ensure normal development.In conclusion,we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.

关键词： N-glycosylation T-cell development Thymocytes Glycocalyx Inflammation

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COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation

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World Journal of Hematology 2024年第1期11卷 1-8页

作者： Milton Artur Ruiz Roberto Luiz Kaiser Junior Lilian Piron-Ruiz Tainara souza pinho Lilian Castiglioni Luiz Gustavo de Quadros Department of Bone Marrow Transplantation Associação Portuguesa de BeneficênciaSão Josédo Rio Preto SP 15090470Brazil Department of surgery Kaiser Hospital DiaSão Josédo Rio Preto 08010-150São PauloBrazil Department of Bone Marrow Transplantation Beneficência Portuguesa HospitalSão Josédo Rio Preto 15090470São PauloBrazil FAMERP Faculdade de Medicina de São Josédo Rio PretoSão Josédo Rio Preto 15090000São PauloBrazil Beneficência Portuguesa Hospital ABC Medical SchoolSão Bernardo 15015110São PauloBrazil

BACKGROUND severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HsCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HsCT.METHODs In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HsCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.REsULTs Among the patients with COVID-19,three,who underwent Auto HsCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUsION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HsCT to treat CD.

关键词： Inflammatory bowel disease Crohn disease sARs-CoV-2 COVID-19 Autologous hematopoietic stem cell transplantation stem cell therapy

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Landslide susceptibility mapping using the infinite slope,sHALsTAB,sINMAP,and TRIGRs models in serra do Mar,Brazil

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Journal of Mountain science 2022年第4期19卷 1018-1036页

作者： Thiago Machado do pinho Oswaldo AUGUsTO FILHO University of sao Paulo Sao CarlosSP13566-590Brazil

slope failure triggered by heavy rainfall is very common in tropical and subtropical regions and a cause of major social and economic damage.Landslide susceptibility maps can be generated using geographical information systems(GIs)and limit equilibrium slope stability models coupled or not to hydrological equations.This study investigated the efficacy of four models used for slope stability analysis in predicting landslide-susceptible areas in a GIs environment.The selected models are the infinite slope,the shallow slope stability model(sHALsTAB),the stability index mapping(sINMAP),and the transient rainfall infiltration and grid-based regional slope-stability(TRIGRs).For comparisons,the authors(a)included the infinite slope equation in all models,(b)clearly defined input parameters and failure triggering mechanisms for each simulation(soil depth,water table height,rainfall intensity),(c)determined appropriate values for each model to obtain stability levels that represented similar hydrogeotechnical conditions,and(d)considered upper-third areas of landslide scars to estimate the reliability of susceptibility maps using validation indices.An intense rainfall event occurred in serra do Mar,Brazil in January 2014 triggered hundreds of landslides and was used for back analysis and evaluation of the slope stability analysis models.When rainfall intensity is not considered,the four models produced very similar results.The most reliable landslide susceptibility map was generated using TRIGRs and considering the granite residual granite soils geological-geotechnical unit,subjected to a rainfall intensity of 210 mm for 2 h under unsaturated conditions.

关键词： Geographical information system safety factor Heavy rainfall Geomechanical parameters Residual soils of phyllite and granite serra do Mar

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High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance strains in Mexico

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1023-1034页

作者： Alexis Jose-Abrego sonia Roman João Renato Rebello pinho Michele soares Gomes-Gouvêa Arturo Panduro Department of Genomic Medicine in Hepatology Civil Hospital of Guadalajara“Fray Antonio Alcalde”GuadalajaraJaliscoMexico Health sciences Center University of GuadalajaraGuadalajaraJaliscoMexico LIM07 Department of GastroenterologyUniversity of São PauloSão PauloBrazil Hospital Israelita Albert Einstein São PauloBrazil

Background and Aims:Lamivudine(3TC),telbivudine(LdT),entecavir(ETV),adefovir(ADF),and tenofovir(TFV)are drugs used to treat hepatitis B virus(HBV)infection,but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities.These mutations have not been thoroughly investigated in Mexico.This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.Methods:This cross-sectional study analyzed 158 samples.HBV DNA was extracted,amplified,and sequenced in serum samples using the spin column method,PCR assay,and sanger’s sequencing,respectively.HBV genotypes were determined,and HBV mutations were tested using the Geno2pheno tool.Results:Overall,68.4%(108/158)of HBV patients were infected with genotype H,followed by G(11.4%,18/158),A2(10.8%,17/158),F1b(6.9.0%,11/158),D(1.9%,3/158),and E(0.6%,1/158),and 5.1%(8/158)had evidence of recombination.The prevalence of resistance mutations was 8.2%(13/158)and the most common combined mutation was rt180M+rt204V.Notably,we found the combinations rt180M+rt204V+rt173L(n=2)and rt180M+rt204V+rt202G(n=1)that confer multidrug resistance to 3TC,LdT,and ETV.Resistance mutations were found in genotypes A2(11.8%,2/17),and H(10.2%,11/108),and escape mutations were detected in HBV genotypes A2(11.8%,2/17),H(10.2%,11/108),F1b(9.1%,1/11)and G(5.6%,1/18).Conclusions:The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H.The earliest cases of HBV multidrug resistance were detected in Mexico.

关键词： Hepatitis B virus Drug resistance mutations Multidrug resistance strain Immune escape

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seismic response of continuous span bridges through fiber-based finite element analysis

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Earthquake Engineering and Engineering Vibration 2006年第1期5卷 119-131页

作者： Chiara Casarotti Rui pinho University of Pavia Structural Mechanics Dept. Via Ferrata 1 27100 Pavia Italy

It is widely recognized that nonlinear time-history analysis constitutes the most accurate way to simulate the response of structures subjected to strong levels of seismic excitation. This analytical method is based on sound underlying principles and has the capability to reproduce the intrinsic inelastic dynamic behavior of structures. Nonetheless, comparisons with experimental results from large-scale testing of structures are still needed, in order to ensure adequate levels of confidence in this numerical methodology. The fiber modelling approach employed in the current endeavor inherently accounts for geometric nonlinearities and material inelasticity, without a need for calibration of plastic hinges mechanisms, typical in concentrated plasticity models. The resulting combination of analysis accuracy and modelling simplicity, allows thus to overcome the perhaps not fully justifiable sense of complexity associated to nonlinear dynamic analysis. The fiber-based modelling approach is employed in the framework of a finite element program downloaded from the Intemet for seismic response analysis of framed structures. The reliability and accuracy of the program are demonstrated by numerically reproducing pseudo-dynamic tests on a four span continuous deck concrete bridge. Modelling assumptions are discussed, together with their implications on numerical results of the nonlinear time-history analyses, which were found to be in good agreement with experimental results.

关键词： bridges seismic response pseudo-dynamic testing nonlinear dynamic analysis fiber modelling

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A remote,fully oriented personalized program of physical exercise for women in follow-up after breast cancer treatment improves body composition and physical fitness

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sports Medicine and Health science 2023年第2期5卷 128-136页

作者： Edipo G.França-Lara saulo H.Weber Ricardo A.pinho JoséClaudio Casali-da-Rocha selene Elifio-Esposito Graduate Program in Health sciences School of Medicine and Life SciencesPontifícia Universidade Católica do ParanáCuritibaPRBrazil school of Medicine and Life sciences Pontifícia Universidade Católica do ParanáCuritibaPRBrazil Oncogenetics Department A.C.Camargo Cancer CenterSão PauloSPBrazil Hospital Erasto Gaertner CuritibaPRBrazil

This study aimed to evaluate the efficacy of an individualized remote exercise program on the improvement of body composition and physical fitness of a heterogeneous group of patients who completed breast cancer treatment.This prospective study included 107 women aged 18 to 60,shortly after curative treatment for localized breast cancer,at the Erasto Gaertner Cancer Hospital(HEG)in Curitiba,PR,Brazil.Body composition,maximal oxygen consumption,and muscle resistance were evaluated after nine months of intervention while considering adherence to the program,level of physical activity,presence of binge eating disorder,tumor classification,and treatment type.seventy-eight women(72.8%)adhered to the training program.Adherent participants showed significant changes in body mass([-4.3±3.6]kg;pss index([-1.6±1.5]kg·m^(−2);psumption([7.5±2.0]ml·kg^(−1)·min^(−1));psistance([11.2±2.8]reps;pst,these variables did not change significantly in the non-adherent group.Among the adherent participants,those subclassified in the severe binge group showed a more noticeable reduction in body mass,body mass index,and body fat(pse in the non-binge group.Individualized remotely-guided physical exercise programs can improve the body composition and physical fitness of women undergoing post-breast cancer surveillance,regardless of pathological history or treatment.

关键词： Breast neoplasm Exercise training Physical therapy modalities Body weight changes Physical functional performance

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Emulsion-filled gels of soy protein isolate for vehiculation of vitamin D3:Effect of protein solubility on their mechanical and rheological characteristics

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Food Bioscience 2022年第1期45卷 75-87页

作者： Letícia s.Ferreira Thais C.Brito-Oliveira samantha C.pinho Laboratory of Encapsulation and Functional Foods Department of Food EngineeringSchool of Animal Science and Food Engineering(FZEA)University of S˜ao Paulo(USP)Av.Duque de Caxias Norte 225–Jd ElitePirassunungaSP13635-900Brazil

The aim of this study was to develop heat-induced gels of soy protein isolate(sPI)filled with Brazil nut oil emulsions encapsulating vitamin D3(VD3).Before gelation,dispersions produced with different sPI concentrations(11-15%,w/w)were subjected to different pretreatments(manual mixing or mechanical stirring at 800 rpm for 10,20,and 30 min)and had their protein solubility quantified.The application of mechanical stirring increased the solubility of proteins and decreased the average particle size,affecting the microstructure(observed by confocal laser scanning microscopy)and rheological properties(evaluated by uniaxial compression and small strain oscillatory tests)of the heat-set gels.The incorporation of emulsions(produced with Brazilian nut oil)into gels formed emulsion filled gels(EFGs),which presented higher Young’s moduli andσH in comparison to non-filled gels(NFGs),indicating that the oil droplets were active within the matrices.The properties of EFGs subjected to small strain oscillatory tests,varied with the pretreatment conditions and sPI concentrations,highlighting the high influence of protein solubility,matrix inhomogeneities,and droplet clustering for determining the properties of such complex systems.Also,the heat-induced emulsion-filled gels of sPI produced were effective in protecting VD3,presenting good retention after 30 days of storage under refrigeration,and represent promising alternative for the production of future food gelled products.

关键词： Emulsion-filled gels soy protein isolate Cholecalciferol Gel structure

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Comparative Heat Transfer Data for solid-Liquid Phase Change of D-Mannitol and Adipic Acid

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Energy and Power Engineering 2022年第11期14卷 680-704页

作者： Ulyana Horbatyuk Ana Magalhães Victor Ferreira Carlos.pinho CEFT DEMEC Faculty of Engineering University of Porto Porto Portugal

The goal of this work was to measure the heat transfer rates from thermofluid, Therminol 66, to two phase change materials, D-mannitol and adipic acid. It concerns the determination of heat transfer coefficients for the design of a concentrated solar energy plant requiring PCM thermal energy storage and is part of a wider set of experiments, where several PCMs were tested. An experimental installation was used with a cylindrical vessel with three tubes disposed almost horizontally (5°inclination), containing the phase change material, around which the thermal fluid flowed almost perpendicular to the tubes. The experimental installation allowed to recreate heating and cooling cycles. In order to evaluate the influence of the flow on the rate at which the heating and cooling processes took place, tests were performed at different thermofluid mass flow rates, concluding that there is no great influence, since the thermal resistance inside the tubes is much higher than on the outside. D-mannitol and adipic acid, present different phase change temperatures, 164°C for D-mannitol and 152°C for adipic acid. The average heat transfer coefficient, during the phase change process, was of 340 W/(msup>2sup>K) for D-mannitol and 1320 W/(msup>2sup>K) for adipic acid.

关键词： Adipic Acid D-Mannitol Heat Transfer Coefficient Phase Change Materials

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The role of exercise in brain DNA damage

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Neural Regeneration Research 2020年第11期15卷 1981-1985页

作者： Thais Cereser Vilela Vanessa Moraes de Andrade Zsolt Radak Ricardo Aurino de pinho Laboratory of Translational Biomedicine Graduate Program of Health SciencesUniversity of Southern Santa Catarina–UNESCCriciumaSCBrazil Research Institute of sport science University of Physical EducationBudapestHungary Laboratory of Exercise Biochemistry in Health Graduate Program in Health SciencesSchool of MedicinePontificia Universidade Catolica do ParanaCuritibaPRBrazil

Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA,which leads to neuronal death.In this way,DNA damage has been implicated in the pathogenesis of neurological disorders,cancer,and aging.Lifestyle factors,such as physical exercise,are neuroprotective and increase brain function by improving cognition,learning,and memory,in addition to regulating the cellular redox milieu.several mechanisms are associated with the effects of exercise in the brain,such as reduced production of oxidants,up-regulation of antioxidant capacity,and a consequent decrease in nuclear DNA damage.Furthermore,physical exercise is a potential strategy for further DNA damage repair.However,the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown.In this review,we discuss the influence of exercise on DNA damage and adjacent mechanisms in the brain.We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage.

关键词： aerobic exercise apoptosis brain-derived neurotrophic factor brain DNA damage DNA repair neurodegenerative disease oxidative stress physical exercise strength exercise

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