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COVID-19 liver and gastroenterology findings:An in silico analysis of SARS-CoV-2 interactions with liver molecules

World Journal of Hepatology 2022年第6期14卷 1131-1141页

作者： Gabrielle Caroline Peiter Cristiano de Bem Torquato de Souza Lucca Miketen de Oliveira Luis Gustavo Pagliarin Valentina Nunes Fontoura dos Anjos filipe antônio frança da silva Fabrício Freire de Melo Kádima Nayara Teixeira Universidade Federal do Paraná Campus ToledoToledo 85919-899ParanáBrazil Universidade Federal da Bahia Campus Anísio TeixeiraVitória da Conquista 45029-094BahiaBrazil

BACKGROUND Coronavirus disease 19(COVID-19)has not only been shown to affect the respiratory system,but has also demonstrated variable clinical presentations including gastrointestinal tract *** addition,abnormalities in liver enzymes have been reported indicating hepatic *** is known that severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)might infect cells via the viral receptor angiotensin-converting enzyme 2(ACE2)which is expressed in several organs including the *** viral Spike glycoprotein binds to ACE2 and must be cleaved by Furin and Type 2 Serine Protease to enter the *** that,the Akt/mTOR signaling pathway is activated and several COVID-19 changes are *** To analyze liver and gastrointestinal symptoms and cell signaling pathways triggered by SARS-CoV-2 infection due to virus-liver interactions in *** In this in silico study,the three-dimensional structures of the Akt,mTORC1 and Furin(receptors)were selected from the Protein data Bank(PDB)and the structures of inhibitors(ligands)MK-2206,CC-223 and Naphthofluorescein were selected from PubChem and ZINC *** files were downloaded as 2D structures and converted to optimized 3D structures using ViewerLite 4.2 *** Sketch®software was used to calculate prediction of the protonated form of inhibitors in a physiological environment(pH 7.4).AutoDock Tools(ADT)software was used to calculate and delimit the Grid box used in the molecular docking of each structure selected in the *** addition,protonated ligands were prepared for molecular docking using ADT *** docking was performed using ADT software tools connected to Vina *** of the amino acid residues involved in ligand interactions,as well as ligand twists,the atoms involved in interactions,bond type and strength of interactions were performed using PyMol^(■)and Discovery Studio^(■)(BIOVIA)*** Molecular docking analysis showed that the mTOR

关键词： Bioinformatics Cell signaling pathway COVID-19 Liver injury SARS-CoV-2

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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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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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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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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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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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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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Transmission of severe acute respiratory syndrome coronavirus 2 via fecal-oral:Current knowledge

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World Journal of Clinical Cases 2021年第28期9卷 8280-8294页

作者： filipe antônio frança da silva Breno Bittencourt de Brito Maria Luísa Cordeiro Santos Hanna Santos Marques Ronaldo Teixeira da silva Júnior Lorena Sousa de Carvalho Samuel de Sousa Cruz Gabriel Reis Rocha Gabriel Lima Correa Santos Kathlen Coutinho de Souza Rebeca Gabrielle Almeida Maciel daiana silva Lopes Natália Oliveira e silva Márcio Vasconcelos Oliveira Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45002175BahiaBrazil Departamento de Ciências Naturais Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45002175BahiaBrazil Departamento de Bioquímica e Biofísica Universidade Federal da BahiaSalvador 40.110-100BahiaBrazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than 93 million cases and 2 million deaths in the ***-CoV-2 respiratory tract infection and its main clinical manifestations such as cough and shortness of breath are well known to the scientific ***,a growing number of studies have reported SARS-CoV-2-related gastrointestinal involvement based on clinical manifestations,such as diarrhea,nausea,vomiting,and abdominal pain as well as on the pathophysiological mechanisms associated with coronavirus disease ***,current evidence suggests SARS-CoV-2 transmission via the fecal-oral route and aerosol ***,studies have shown a high risk of contamination through hospital surfaces and personal ***,viable SARS-CoV-2 specimens can be obtained from aerosols,which raises the possibility of transmission through aerosolized viral particles from ***,the infection by SARS-CoV-2 via fecal-oral route or aerosolized particles should *** addition,a possible viral spread to sources of drinking water,sewage,and rivers as well as the possible risk of viral transmission in shared toilets become a major public health concern,especially in the least developed *** authors have emphasized the presence of viral RNA and even viable SARS-CoV-2 in human feces,studies on the possible fecal-oral coronavirus disease 2019 transmission become essential to understand better the dynamics of its transmission and,then,to reinforce preventive measures against this infection,leading to a more satisfactory control of the incidence of the infection.

关键词： COVID-19 SARS-CoV-2,Transmission Via fecal-oral

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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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