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Role of polymorphisms in genes that encode cytokines and Helicobacter pylori virulence factors in gastric carcinogenesis

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World Journal of Clinical Oncology 2018年第5期9卷 83-89页

作者： breno bittencourt de brito Filipe Ant?nio Fran?a da Silva Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da Bahia

The Helicobacter pylori(H. pylori) infection is a determinant factor in gastric cancer(GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin(IL)-1β, IL-1 Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxinassociated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.

关键词： Helicobacter pylori Virulence factors Cytokines Gene polymorphisms Gastric cancer

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Molecular docking of DS-3032B,a mouse double minute 2 enzyme antagonist with potential for oncology treatment development

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World Journal of Clinical Oncology 2022年第6期13卷 496-504页

作者： Vítor Hugo Sales da Mota Fabrício Freire de Melo breno bittencourt de brito Filipe Antônio França da Silva Kádima Nayara Teixeira Campus Toledo Universidade Federal do ParanáToledo 85.919-899ParanáBrazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

BACKGROUND It is known that p53 suppression is an important marker of poor prognosis of cancers,especially in solid tumors of the breast,lung,stomach,and esophagus;liposarcomas,glioblastomas,and *** p53 has mouse double minute 2(MDM2)as its primary negative regulator,this molecular docking study seeks to answer the following hypotheses:Is the interaction between DS-3032B and MDM2 stable enough for this drug to be considered as a promising neoplastic inhibitor?AIM To analyze,in silico,the chemical bonds between the antagonist DS-3032B and its binding site in *** For molecular docking simulations,the file containing structures of MDM2(receptor)and the drug DS-3032B(ligand)were *** three-dimensional structure of MDM2 was obtained from Protein Data Bank,and the one for DS-3032B was obtained from PubChem *** location and dimensions of the Grid box was determined using AutoDock Tools *** this case,the dimensions of the Grid encompassed the entire *** ligand DS-3032B interacts with the MDM2 receptor in a physiological environment with pH 7.4;thus,to simulate more reliably,its interaction was made with the calculation for the prediction of its protonation state using the MarvinSketch®*** ligands,with and without the protonation,were prepared for molecular docking using the AutoDock Tools *** software detects the torsion points of the drug and calculates the angle of the *** docking simulations were performed using the tools of the AutoDock platform connected to the Vina *** analyses of the amino acid residues involved in the interactions between the receptor and the ligand as well as the twists of the ligand,atoms involved in the interactions,and type,strength,and length of the interactions were performed using the PyMol software(***/2)and Discovery Studio from BIOVIA®.RESULTS The global alignment indicated crystal structure 5SWK was more suitable for docking simulati

关键词： DS-3032B Mouse double minute 2 antagonist Molecular docking Tumor suppressor p53

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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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Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil

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World Journal of Experimental Medicine 2022年第5期12卷 100-103页

作者： Fabrício Freire de Melo Lilian Martins Oliveira Diniz JoséNélio Januário João Fernando Gonçalves Ferreira Rafael Santos Dantas Miranda Dórea breno bittencourt de brito Hanna Santos Marques Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Dulciene Maria de Magalhães Queiroz Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil departamento de Pediatria Universidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Núcleo de Ações e Pesquisa em Apoio Diagnóstico Universidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Laboratory of Research in Bacteriology Universidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Laboratory of Bacteriology Faculdade de MedicinaUniversidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45029-094Brazil

Qualitative antibody tests are an easy,point-of-care diagnostic method that is useful in diagnosing coronavirus disease 2019,especially in situations where reverse transcription-polymerase chain reaction is ***,some factors are able to affect its sensitivity and accuracy,which may contribute to these tests not being used as a first-line diagnostic tool.

关键词： Serological test IgM IgG COVID-19 Diagnosis Antibody

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Influence of the COVID-19 pandemic in the gastrointestinal oncology setting:An overview

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World Journal of Gastrointestinal Pathophysiology 2022年第5期13卷 157-169页

作者： breno bittencourt de brito Hanna Santos Marques Filipe Antônio França da Silva Maria Luísa Cordeiro Santos Glauber Rocha Lima Araújo Lara de Araujo Valente 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 45055-380BahiaBrazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094Brazil

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been impacting healthcare in various ways worldwide and cancer patients are greatly affected by the coronavirus disease 2019(COVID-19)*** reorganization of the health facilities in order to supply the high demand resulting from the aforementioned infection as well as the social isolation measures led to impairments for the diagnosis and follow-up of patients with gastrointestinal cancers,which has had an impact on the prognosis of the oncologic *** that context,health authorities and organizations have elaborated new guidelines with specific recommendations for the management of individuals with gastrointestinal neoplasms during the *** note,oncologic populations seem to be more susceptible to unfavorable outcomes when exposed to SARS-CoV-2 infection and some interactions involving virus,tumor,host immune system and anticancer therapies are probably related to the poorer prognosis observed in those COVID-19 ***,vaccination stands out as the main prevention method against severe SARS-CoV-2 infection and some particularities have been observed regarding the seroconversion of vaccinated oncologic patients including those with gastrointestinal *** this minireview,we gather updated information regarding the influence of the pandemic in the diagnosis of gastrointestinal neoplasms,new recommendations for the management of gastrointestinal cancer patients,the occurrence of SARSCoV-2 infection in those individuals and the scenario of the vaccination against the virus in that population.

关键词： Gastrointestinal cancer COVID-19 Treatment Diagnosis Vaccination Pandemic

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Helicobacter pylori infection: Beyond gastric manifestations

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World Journal of Gastroenterology 2020年第28期26卷 4076-4093页

作者： Maria Luisa Cordeiro Santos breno bittencourt de brito Filipe Antonio França da Silva Mariana Miranda Sampaio Hanna Santos Marques Natalia Oliveira e Silva Dulciene Maria de Magalhaes Queiroz Fabricio Freire de Melo Instituto Multidisciplinar em Saude Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Universidade Estadual da Bahia Vitória da Conquista 45083-900BahiaBrazil Laboratory of Research in Bacteriology Faculdade de MedicinaUniversidade Federal de Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil

Helicobacter pylori(***)is a bacterium that infects more than a half of world’s *** it is mainly related to the development of gastroduodenal diseases,several studies have shown that such infection may also influence the development and severity of various extragastric *** to the current evidence,whereas this bacterium is a risk factor for some of these manifestations,it might play a protective role in other pathological *** that context,when considered the gastrointestinal tract,*** positivity have been related to Inflammatory Bowel Disease,Gastroesophageal Reflux Disease,Non-Alcoholic Fatty Liver Disease,Hepatic Carcinoma,Cholelithiasis,and ***,lower serum levels of iron and vitamin B12 have been found in patients with *** infection,leading to the emergence of anemias in a portion of *** regards to neurological manifestations,a growing number of studies have associated that bacterium with multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,and Guillain-Barré***,the risk of developing cardiovascular disorders,such as atherosclerosis,is also influenced by the *** that,the ***-associated inflammation may also lead to increased insulin resistance,leading to a higher risk of diabetes mellitus among infected ***,the occurrence of dermatological and ophthalmic disorders have also been related to that *** this sense,this minireview aims to gather the main studies associating *** infection with extragastric conditions,and also to explore the main mechanisms that may explain the role of *** in those diseases.

关键词： Helicobacter pylori Extragastric Neurological Cardiovascular Autoimmune Ophthalmic Diabetes Timeline Treatment

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Tertiary peritonitis: A disease that should not be ignored

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World Journal of Clinical Cases 2021年第10期9卷 2160-2169页

作者： Hanna Santos Marques Glauber Rocha Lima Araújo Filipe Antônio França da Silva breno bittencourt de brito Paulo Victor Dias Versiani Jaqueline Silva Caires Thiago de Carvalho Milet Fabrício Freire de Melo Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45083-900BahiaBrazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil department of Surgery Hospital Geral de Vitória da ConquistaVitória da Conquista 45029-094BahiaBrazil

Intra-abdominal infections can be classified into uncomplicated or complicated(peritonitis). Peritonitis is divided into primary, secondary, and tertiary. Tertiaryperitonitis is the less common but the most severe among peritonitisstratifications, being defined as a recurrent intra-abdominal infection that occurs48 h after a well-succeeded control of a secondary peritonitis. This disease has acomplex pathogenesis that is closely related to the capacity of the peritonealcavity to activate immunological processes. Patients who progress to persistentperitonitis are at an increased risk of developing several infectious complicationssuch as sepsis and multiple organ failure syndrome. Moreover, tertiary peritonitisremains an important cause of hospital death mainly among patients withassociated risk factors. The microbiological profile of organisms causing tertiaryperitonitis is often different from that observed in other types of peritonitis. Inaddition, there is a high prevalence of multidrug-resistant pathogens causing thiscondition, and an appropriate and successful clinical management depends on anearly diagnosis, which can be made easier with the use of clinical scorespresenting a good prediction value during the intensive care unit ***, immediate therapy should be performed to control theinfectious focus and to prevent new recurrences. In this sense, the treatment isbased on initial antimicrobial therapy and well-performed peritoneal drainage.

关键词： Tertiary peritonitis Pathogenesis Clinical manifestation Diagnosis Treatment Prognosis

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Pathogenesis and clinical management of Helicobacter pylori gastric infection

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World Journal of Gastroenterology 2019年第37期25卷 5578-5589页

作者： breno bittencourt de brito Filipe Ant?nio Fran?a da Silva Aline Silva Soares Vinícius Afonso Pereira Maria Luísa Cordeiro Santos Mariana Miranda Sampaio Pedro Henrique Moreira Neves Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da Bahia

Helicobacter pylori(***)is a gram-negative bacterium that infects approximately 4.4 billion individuals ***,its prevalence varies among different geographic areas,and is influenced by several *** infection can be acquired by means of oral-oral or fecal-oral transmission,and the pathogen possesses various mechanisms that improve its capacity of mobility,adherence and manipulation of the gastric microenvironment,making possible the colonization of an organ with a highly acidic *** addition,*** presents a large variety of virulence factors that improve its pathogenicity,of which we highlight cytotoxin associated antigen A,vacuolating cytotoxin,duodenal ulcer promoting gene A protein,outer inflammatory protein and gamma-glutamyl *** host immune system,mainly by means of a Th1-polarized response,also plays a crucial role in the infection *** most ***-positive individuals remain asymptomatic,the infection predisposes the development of various clinical conditions as peptic ulcers,gastric adenocarcinomas and mucosa-associated lymphoid tissue *** and non-invasive diagnostic methods,each of them with their related advantages and limitations,have been applied in *** ***,bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection,and new therapy alternatives are being tested to improve *** *** but not least,the development of effective vaccines against *** infection have been the aim of several research studies.

关键词： Helicobacter pylori Virulence factors Immune response Antibiotics Vaccines

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Epidemiological and clinical characteristics of COVID-19 in a Brazilian public hospital

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World Journal of Clinical Cases 2023年第8期11卷 1761-1770页

作者： Fillipe Dantas Pinheiro Luana Weber Lopes Rafael Santos Dantas Miranda Dórea Glauber Rocha Lima Araújo Filipe Antônio França da Silva breno bittencourt de brito Maria Luísa Cordeiro Santos Geovani Moreno Santos Júnior Maria Teresa Araújo de Lorenzo Barcia Renata de Amorim Marques AndréBezerra Botelho Anna Carolina Saúde Dantas Davi Tanajura Costa Adriano Fernandes Teixeira Cláudio Lima Souza Lucas Miranda Marques Guilherme Barretos Campos Márcio Vasconcelos Oliveira Dulciene Maria de Magalhães Queiroz Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Hospital Geral de Vitória da Conquista Vitória da Conquista 45030-160BahiaBrazil departamento de Ciências da Saúde Universidade Estadual do Sudoeste da Bahia(UESB)Vitória da Conquista 45083-900BahiaBrazil Faculdade de Medicina Universidade Federal de Minas GeraisBelo Horizonte 31270-901Minas GeraisBrazil

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has become a major health concern *** that context,the understanding of epidemiological and clinical features associated with the disease and its severity is crucial for the establishment of strategies aimed at disease control and *** To describe epidemiological features,signs,symptoms,and laboratory findings among severely ill COVID-19 patients from an inten-sive care unit in northeastern Brazil as well as to evaluate predictor factors for disease *** This is a prospective single-center study that evaluated 115 patients admitted to the intensive care unit in a northeastern Brazilian *** The patients had a median age of 65.60±15.78 *** was the most frequent symptom,affecting 73.9%of the patients,followed by cough(54.7%).Fever was reported in approximately one-third of patients and myalgia in 20.8%of the *** least two comorbidities were found in 41.7%of the patients,and hypertension was the most prevalent(57.3%).In addition,having two or more comorbidities was a predictor of mortality,and lower platelet count was positively associated with *** and vomiting were two symptoms that were predictors of death,and the presence of a cough was a protective *** This is the first report of a negative correlation between cough and death in severely ill severe acute respiratory syndrome coronavirus 2-infected *** associations between comorbidities,advanced age,and low platelet count and the outcomes of the infection were similar to the results of previous studies,highlighting the relevance of these features.

关键词： COVID-19 Epidemiology Symptoms Comorbidities Laboratory parameters

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From Helicobacter pylori infection to gastric cancer:Current evidence on the immune response

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World Journal of Clinical Oncology 2022年第3期13卷 186-199页

作者： Vinícius Lima de Souza Gonçalves Maria Luísa Cordeiro Santos Marcel Silva Luz Hanna Santos Marques breno bittencourt de brito Filipe Antônio França da Silva Cláudio Lima Souza Márcio Vasconcelos Oliveira Fabrício Freire de Melo Universidade Estadual do Sudoeste da Bahia Campus Vitória da ConquistaVitória da Conquista 45083-900BahiaBrazil Universidade Federal da Bahia Instituto Multidisciplinar em SaúdeVitória da Conquista 45029-094BahiaBrazil

Gastric cancer(GC)is the result of a multifactorial process whose main components are infection by Helicobacter pylori(***),bacterial virulence factors,host immune response and environmental *** development of the neoplastic microenvironment also depends on genetic and epigenetic changes in oncogenes and tumor suppressor genes,which results in deregulation of cell signaling pathways and apoptosis *** review summarizes the main aspects of the pathogenesis of GC and the immune response involved in chronic inflammation generated by ***.

关键词： Gastric cancer Helicobacter pylori Chronic inflammation Host immune response

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