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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： Luis Guilherme de Oliveira Silva Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos santos Calmon Gabriel Lima Correa santos Gabriel Reis Rocha Fabrício Freire de melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases ***,due to its complexity,it ranks 7th in the list of the most lethal cancers *** pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and *** in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,*** this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy *** is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive *** to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as *** this way,finding new strategies that make it possible to manipulate resistance mechanisms is ***,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC ***,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating thi

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

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Effectiveness of different biochars in remediating a salt-affected Luvisol in Northeast Brazil

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Biochar 2021年第2期3卷 149-159页

作者： wallace melo dos santos Maria Isidoria Silva Gonzaga JoséAiron da Silva AndréQuintão de Almeida JoséCarlos de Jesus santos Thomas Antonio Silva Gonzaga Idamar da Silva Lima EloáMoura Araújo Water Resources Graduate Program Federal University of SergipeSão CristóvãoSE 49100‑000Brazil Agronomy Department Federal University of SergipeSão CristóvãoSE 49100‑000Brazil Agriculture Engineering Department Federal University of SergipeSão CristóvãoSE 49100‑000Brazil University of Notre Dame Notre DameIN 46556USA Soils and Agricultural Engineering Department Federal University of ParanáCuritibaPR 80060‑000Brazil

Biochar has been proposed as a soil amendment to reclaim salt-affected ***,the evaluation of the different biochar types in these soils is essential due to the significant variation among biochar *** this study,biochars from sugarcane bagasse(SB),orange bagasse(OB),and corncob(CB)were applied alone and in the presence of gypsum(G)to test their potential to remediate a highly degraded saline-sodic soil in Brazil´s Northeast *** that,we conducted a laboratory column-leaching experiment and a greenhouse *** the column-leaching test,we analyzed the sodium adsorption ratio(SAR),the electrical conductivity of the saturation extract(ECe),the concentrations of major ions,and the exchangeable sodium percentage(ESP).Maize plants were grown in the leached soil in a ***-and corncob-derived biochars were more efficient than gypsum in reducing the soil salinity,bringing the indicators below threshold values,and optimizing soil reclamation *** ECe,SAR,and ESP were reduced to 3.42 dS m−1,1.64(mmolc dm−3)0.5 and 4.86%,respectively,in the SB treatment;and to 3.19 dS m−1,0.88(mmolc dm−3)0.5 and 2.53%,respectively,in the CB *** bagasse biochar did not effectively reduce the salinity *** biochar treatments improved seed germination and plant *** SB,CB,SBG,and CBG treatments increased plant height(478–558%),shoot mass(783–983%),and root mass(386–500%),***,the application of SB and CB is an effective alternative to remediate saline-sodic soils and to reduce the impact of soil salinity in the environment.

关键词： Biochar Soil remediation Soil salinity Corn growth

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Long chikungunya?An overview to immunopathology of persistent arthralgia

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World Journal of Virology 2024年第2期13卷 48-57页

作者： Jayme Euclydes Picasky Silveira-Freitas Maria Luiza Campagnolo Mariana dos santos Cortez Fabrício Freire de melo Ana Carla Zarpelon-Schutz Kádima Nayara Teixeira Campus Toledo Universidade Federal do ParanáToledoParaná85919-899Brazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaCampus Anísio TeixeiraVitória da ConquistaBahia 45029-094Brazil Programa de Pós-graduação em Biotecnologia PalotinaUniversidade Federal do Paraná-Setor PalotinaParaná85950-000Brazil Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular PalotinaUniversidade Federal do Paraná-Setor PalotinaParaná85950-000Brazil

Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent *** clinical signs triggered by the Chikungunya virus are similar to those of other ***,fever starts abruptly and reaches high levels,followed by severe polyarthralgia and myalgia,as well as an erythematous or petechial maculopapular rash,varying in severity and *** 40%to 60%of affected individuals report persistent arthralgia,which can last from months to *** symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune *** main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Βligand and bone *** review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages,leading to local infiltration of CD4+T cells,which sustains the inflammatory process in the joints through the secretion of pro-inflammatory *** term"long chikungunya"was used in this review to refer to persistent arthralgia since,due to its manifestation over long periods after the end of the viral infection,this clinical condition seems to be characterized more as a sequel than as a symptom,given that there is no active infection involved.

关键词： Chikungunya Immunopathology Inflammation process Persistent arthralgia Signaling lymphocytic activation molecule family member 7

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Laminated Solid Timber Slab with Transverse Prestressing Using the Strategy of Interleaved Vertical Displacement of Lamellae

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Journal of Civil Engineering and Architecture 2024年第4期18卷 186-198页

作者： Bianca Bispo dos Reis Jorge Daniel de melo Moura Marcos Vinício de Camargo Everaldo Pletz Graduate Program in Architecture and Urbanism Londrina State UniversityJardim Portal de Versalhes 1Londrina 86057-970PRBrazil Department of Civil Engineering Federal Technological University of Paraná(UTFPR)Apucarana 86812-460PRBrazil Retired professor Department of Structural Engineering Londrina State UniversityLondrina 86057-970PRBrazil

This article presents a study on the structural behavior of transversely prestressed laminated timber slabs,focusing on an innovative approach:vertically misaligned *** misalignment,achieved by sliding vertically the wooden lamellae rather than aligning them,enhances the slab’s cross-section moment of inertia,thereby improving load-bearing capacity and *** involved two groups of structural size specimens:one with vertically aligned lamellae(control group)and the other with misaligned lamellae(study group).Results showed the study group exhibited 42%superior stiffness and 10%less load capacity compared to the *** typically occurred individually in the lamellae,particularly in those with defects or lower modulus of elasticity,concentrated in the middle third of the slabs’free span where tensile stresses *** a higher number of failed lamellae,the study group demonstrated promising *** of prestressing bar indicated no damage at all in the thread,suggesting potential for reducing bar *** findings offer crucial insights into applying these slabs in timber construction as well as to any kind of construction.

关键词： Transversal prestressed slabs wooden construction plantation wood flexural testing design methodology

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Experimental evidence of pressure effects on spinel dissolution and peridotite serpentinization kinetics under shallow hydrothermal conditions

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Geoscience Frontiers 2024年第2期15卷 236-250页

作者： Yuri de melo Portella Rommulo Vieira Conceição Tiago Abreu Siqueira Lucas Bonan Gomes Rodrigo Sebastian Iglesias Programa de Pós-Graduação em Geociências(PPGGEO) Universidade Federal do Rio Grande do SulPorto AlegreBrazil Petrobras–Petróleo Brasileiro S.A. Avenida Henrique Valadares 28CentroRio de Janeiro(RJ)20231-030Brazil Instituto do Petróleo e dos Recursos Naturais-PUCRS–Pontifícia Universidade Católica do Rio Grande do Sul 90619-900Porto AlegreBrazil Universidade Federal do Rio Grande do Sul Instituto de GeociênciasLaboratório de Difratometria de Raios XPorto AlegreBrazil Escola Politécnica–PUCRS-Pontifícia Universidade Católica do Rio Grande do Sul 90619-900 Porto AlegreBrazil

Serpentinization reactions are paramount to understand hydro-geothermal activity near plate boundaries and mafic–ultramafic massifs,as well as fluid and element transfer between the Earth’s mantle and ***,fluid-rock element exchange and serpentinization kinetics under shallow hydrothermal conditions is still largely *** we present two constant temperature(230℃)time-series of natural peridotite(77.5%olivine;13.7%enstatite;6.8%diopside;2%spinel)serpentinization experiments:at 13.4 MPa;and 20.7 ***-enriched lizardite was the main secondary mineral in all runs after olivine(olv)and orthopyroxene(opx)serpentinization(without any detectable brucite,talc or magnetite),while primary spinel and diopside partially dissolved during the *** serpentinization stages comprises intrinsically coupled reactions between olivine and enstatite,as Al and Si are progressively transferred from orthopyroxene-derived to olivine-derived serpentine,while the opposite is true for Mg and Fe,with homogenization of serpentines compositions after 40 *** Ni/Cr ratios of serpentines,however,remain diagnostic of the respective primary *** average serpentine content indicates fast serpentinization rates of 0.55 wt.%·day^(-1)(0.26 mmol·day^(-1))and 0.26 wt.%·day^(-1)(0.13 mmol·day^(-1))at 13.4 and 20.7 MPa,*** 2x faster serpentinization kinetics at lower pressure is likely linked to enhanced spinel dissolution leading to one order of magnitude higher available Al,which accelerates olivine serpentinization while delays orthopyroxene ***,time-dependent increase in solid products masses suggests rock volume expands linearly 0.37%±0.01%per serpentine wt.%independently of *** balance constrains suggests olv:opx react at~5:2 and~3:2 M ratios,resulting in Si-deficient and Si-saturated serpentines at the end of the low-pressure series(13.4 MPa)and high-pressure series(20.7 MPa),***

关键词： Serpentine Volume expansion Serpentinization fluids Lost City hydrothermal field Serpentinite-hosted hydrothermal systems Hydrogen(H_(2))generation

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Didactic Sequences as an Educational Product to Facilitate Teaching-Learning Processes in Lato Sensu Graduate Courses in the Area of Health Management in Primary Care

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Health 2023年第6期15卷 495-506页

作者： Lidiane Medeiros melo David dos santos Calheiros Centro de Ciências Integradoras (CCI) Universidade Estadual de Ciências da Saúde de Alagoas (UNCISAL) Maceió Brasil

Teaching strategies can be considered as techniques that are constructed to be used with the objective of promoting teaching and learning in the classroom, so that the teacher is considered a mentor, as he is the one who selects, analyzes, studies, organizes, builds and proposes the most classic tools to facilitate the learning process [1]. This study is an experience report related to the construction of an educational product that consists of the elaboration of pedagogical strategies, characterized by five didactic sequences in the perspective of collaborating with teaching-learning processes in lato sensu graduate courses. The themes that are part of the didactic sequences were built based on the results obtained in scientific research carried out during the development of the strict sensu postgraduate course in Teaching in Health and Technology, which involved: the work of coordinators who work in the field of health management in Primary Care, situations that challenge the management of Primary Care and the potentialities of work in the management of Primary Care. The didactic sequences have fun teaching strategies that provide meaningful learning for a future qualified professional performance. These sequences involve the use of active methodologies and the use of digital tools. The educational product developed seeks to promote benefits that can collaborate with the improvement of Primary Care Management and teaching-learning processes in the training of health professionals. Therefore, the pedagogical strategies, as well as its entire construction process, were developed through the collaboration of professors of the Health and Society discipline at the State University of Health Sciences of Alagoas (UNCISAL), seeking to make it qualify for effective construction of knowledge and that promote its wide use in the academic environment.

关键词： Educational Products Primary Health Care Health Management

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Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection

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World Journal of Gastroenterology 2023年第30期29卷 4604-4615页

作者： Gabriella Feilstrecker Balani Mariana dos santos Cortez Jayme Euclydes Picasky da Silveira Freitas Fabrício Freire de melo Ana Carla Zarpelon-Schutz Kádima Nayara Teixeira Campus Toledo Universidade Federal do ParanáToledo 85.919-899ParanáBrazil Campus Anísio Teixeira Universidade Federal da BahiaInstituto Multidisciplinar em SaúdeVitória da Conquista 45.029-094BahiaBrazil Programa de Pós-graduação em Biotecnologia-Setor Palotina Universidade Federal do ParanáPalotina 85.950-000ParanáBrazil Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular-Setor Palotina Universidade Federal do ParanáPalotina 85.950-000ParanáBrazil

Many studies point to an association between Helicobacter pylori(***)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of *** appears that *** infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune *** gut immune response appears to be modulated by *** infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue ***,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is *** immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such *** neutrophil-activating protein,but also with microenvironmental changes that favor permanence of *** in the *** changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the ***,there is a causal relationship between *** infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

关键词： Cytotoxin-associated antigen A oncoprotein Gut microbiota Helicobacter pylori Helicobacter pylori neutrophilactivating protein Immunological modulation Inflammatory bowel disease NLR family pyrin domain containing 3 inflammasome

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Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

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World Journal of Gastroenterology 2023年第14期29卷 2202-2221页

作者： Fabian Fellipe Bueno Lemos Caroline Tianeze de Castro Mariana santos Calmon Marcel Silva Luz Samuel Luca Rocha Pinheiro Clara Faria Souza Mendes dos santos Gabriel Lima Correa santos Hanna santos Marques Henrique Affonso Delgado Kádima Nayara Teixeira Cláudio Lima Souza Márcio Vasconcelos Oliveira Fabrício Freire de melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45029094BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919899ParanáBrazil

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(***)-induced chronic *** practice guidelines currently recommend *** eradication as the preferred initial treatment for early-stage *** determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is *** To perform a meta-analysis to assess the rate of complete remission(CR)of ***-positive early-stage GML following bacterial *** We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September *** and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in ***-positive *** risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal *** pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects *** and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P50%,*** and meta-regression analyses were conducted to explore potential sources of *** The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text ***,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational *** overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 ***-positive early-stage GML patients,in whom *** was successfully eradicated,were incl

关键词： Lymphoma B-cell Marginal zone Gastric mucosa-associated lymphoid tissue lymphoma Stomach lymphoma Helicobacter pylori Therapeutics Eradication therapy

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Autophagy, apoptosis and organelle features during cell exposure to cadmiumč

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BIOCELL 2013年第2期37卷 45-54页

作者： CRISTIANE dos santos VERGILIO EDÉSIO JOSÉTENÓRIO DE melo Universidade Estadual do Norte Fluminense Centro de Biociências e BiotecnologiaLaboratório de Biologia Celular e TecidualCampos dos GoytacazesRJBrasil28013-602.

Cadmium(Cd)induces several effects in different tissues,but our knowledge of the toxic effects on organelles is insuffi *** observe the progression of Cd effects on organelle structure and function,HuH-7 cells(human hepatic carcinoma cell line)were exposed to CdCl2 in increasing concentrations(1μM–20μM)and exposure times(2 h–24 h).During Cd treatment,the cells exhibited a progressive decrease in viability that was both time-and *** treated cells displayed progressive morphological changes that included cytoplasm retraction and nuclear condensation preceding a total loss of cell *** with 10μM for 12 h led to irreversible *** these drastic and irreparable damages,treated cells(5μM for 12 h)presented a progressive loss of mitochondrial function and cytoplasm acidifi cation as well as dysfunction and disorganization of microfi laments and endoplasmic *** damages led to the induction of apoptotic events and an increase in autophagic bodies in the *** results revealed that Cd affects multiple intra-cellular targets that induce alterations in the mitochondria,cytoskeleton,endoplasmic reticulum and acidic compartments,ultimately culminating in cell death via apoptotic and autophagic pathways.

关键词： Cd cell death hepatocyte HuH-7 cells mitochondria

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Non-pharmacological management of pediatric functional abdominal pain disorders:Current evidence and future perspectives

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World Journal of Clinical Pediatrics 2022年第2期11卷 105-119页

作者： Maria Luísa Cordeiro santos Ronaldo Teixeira da Silva Júnior Breno Bittencourt de Brito Filipe Antônio França da Silva Hanna santos Marques Vinícius Lima de SouzaGonçalves Talita Costa dos santos Carolina Ladeia Cirne Natália Oliveira e Silva Márcio Vasconcelos Oliveira Fabrício Freire de melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45083-900BahiaBrazil

Functional abdominal pain disorders(FAPDs) are an important and prevalent cause of functional gastrointestinal disorders among children, encompassing the diagnoses of functional dyspepsia, irritable bowel syndrome, abdominal migraine, and the one not previously present in Rome Ⅲ, functional abdominal pain not otherwise specified. In the absence of sufficiently effective and safe pharmacological treatments for this public problem, non-pharmacological therapies emerge as a viable means of treating these patients, avoiding not only possible side effects, but also unnecessary prescription, since many of the pharmacological treatments prescribed do not have good efficacy when compared to placebo. Thus, the present study provides a review of current and relevant evidence on non-pharmacological management of FAPDs, covering the most commonly indicated treatments, from cognitive behavioral therapy to meditation, acupuncture, yoga, massage, spinal manipulation, moxibustion, and physical activities. In addition, this article also analyzes the quality of publications in the area, assessing whether it is possible to state if non-pharmacological therapies are viable, safe, and sufficiently well-based for an appropriate and effective prescription of these treatments. Finally, it is possible to observe an increase not only in the number of publications on the non-pharmacological treatments for FAPDs in recent years, but also an increase in the quality of these publications. Finally, the sample selection of satisfactory age groups in these studies enables the formulation of specific guidelines for this age group, thus avoiding the need for adaptation of prescriptions initially made for adults, but for children use.

关键词： Functional abdominal pain disorder Pediatrics Rome IV Behavioral intervention Nonpharmacological treatment Complementary medicine

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