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1.
Int J Med Microbiol ; 304(3-4): 300-6, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24373859

RESUMEN

To compare children and adults in respect to the effect of H. pylori infection on the gastric concentrations of cytokines linked to innate and Th1 immune response, as well as to investigate the changes in the gastric concentrations of the studied cytokines according to the age. We studied 245 children (142 H. pylori-negative and 103 H. pylori-positive) and 140 adults (40 H. pylori-negative and 100 H. pylori-positive). The gastric concentrations of cytokines representative of the innate and Th1 response were higher in the H. pylori-positive than in the -negative children and adults. The gastric concentrations of IL-1α and TNF-α were significantly higher, while those of IL-2, IL-12p70 and IFN-γ were lower in the infected children than in the infected adults. In the infected children, the gastric concentration of IL-1α, IL-2, IL-12p70 and IFN-γ increased, whereas in adults, the gastric concentrations of IFN-γ and IL-12p70 decreased with the aging. Increased gastric concentration of Th1 associated cytokines correlated with increased degree of gastritis that is the background lesion for the development of the H. pylori associated severe diseases. Concluding, Th1 response to H. pylori infection varies according to the age and seems to have determinant implication in the H. pylori infection outcomes.


Asunto(s)
Mucosa Gástrica/inmunología , Mucosa Gástrica/patología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/patología , Helicobacter pylori/inmunología , Células TH1/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Citocinas/análisis , Femenino , Mucosa Gástrica/química , Infecciones por Helicobacter/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
2.
World J Clin Oncol ; 15(4): 496-522, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38689629

RESUMEN

Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

3.
World J Gastroenterol ; 30(6): 579-598, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38463019

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) infection has been well-established as a significant risk factor for several gastrointestinal disorders. The urea breath test (UBT) has emerged as a leading non-invasive method for detecting H. pylori. Despite numerous studies confirming its substantial accuracy, the reliability of UBT results is often compromised by inherent limitations. These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H. pylori infection. AIM: To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H. pylori infection in adult patients with dyspepsia. METHODS: We conducted an independent search of the PubMed/MEDLINE, EMBASE, and Cochrane Central databases until April 2022. Our search included diagnostic accuracy studies that evaluated at least one of the index tests (13C-UBT or 14C-UBT) against a reference standard. We used the QUADAS-2 tool to assess the methodological quality of the studies. We utilized the bivariate random-effects model to calculate sensitivity, specificity, positive and negative test likelihood ratios (LR+ and LR-), as well as the diagnostic odds ratio (DOR), and their 95% confidence intervals. We conducted subgroup analyses based on urea dosing, time after urea administration, and assessment technique. To investigate a possible threshold effect, we conducted Spearman correlation analysis, and we generated summary receiver operating characteristic (SROC) curves to assess heterogeneity. Finally, we visually inspected a funnel plot and used Egger's test to evaluate publication bias. RESULTS: The titles and abstracts of 4621 studies were screened; 79 articles were retrieved and selected for full-text reading. Finally, 60 studies were included in the diagnostic test accuracy meta-analysis. Our analysis demonstrates superior diagnostic accuracy of 13C-UBT over 14C-UBT, indicated by higher sensitivity (96.60% vs 96.15%), specificity (96.93% vs 89.84%), likelihood ratios (LR+ 22.00 vs 10.10; LR- 0.05 vs 0.06), and area under the curve (AUC; 0.979 vs 0.968). Notably, 13C-UBT's DOR (586.47) significantly outperforms 14C-UBT (DOR 226.50), making it the preferred diagnostic tool for dyspeptic individuals with H. pylori infection. Correlation analysis revealed no threshold effect (13C-UBT: r = 0.48; 14C-UBT: r = -0.01), and SROC curves showed consistent accuracy. Both 13C-UBT and 14C-UBT showed high AUC values (13C-UBT 0.979; 14C-UBT 0.968) near 1.00, reinforcing their excellent accuracy and endorsing both as reliable diagnostic tools in clinical practice. CONCLUSION: In summary, our study has demonstrated that 13C-UBT has been found to outperform the 14C-UBT, making it the preferred diagnostic approach. Additionally, our results emphasize the significance of carefully considering urea dosage, assessment timing, and measurement techniques for both tests to enhance diagnostic precision. Nevertheless, it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Adulto , Humanos , Infecciones por Helicobacter/diagnóstico , Urea , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pruebas Respiratorias/métodos , Pruebas Diagnósticas de Rutina
4.
World J Gastroenterol ; 29(32): 4851-4859, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37701138

RESUMEN

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma, trailing behind diffuse large B-cell lymphoma and follicular lymphoma. Gastric mucosa-associated lymphoid tissue lymphoma (GML) is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori (H. pylori)-induced chronic gastritis. On the other hand, a specific subset of individuals diagnosed with GML does not exhibit H. pylori infection. In contrast to its H. pylori-positive counterpart, it was previously believed that H. pylori-negative GML was less likely to respond to antimicrobial therapy. Despite this, surprisingly, in-creasing evidence supports that a considerable proportion of patients with H. pylori-negative GML show complete histopathological remission after bacterial eradication therapy. Nonetheless, the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended. In recent years, there has been growing interest in investigating the role of non-H. pylori gastric helicobacters (NHPHs) in the pathogenesis of H. pylori-negative GML. However, additional research is required to establish the causal relationship between NHPHs and GML. In this minireview, we examined the current understanding and proposed prospects on the involvement of NHPHs in H. pylori-negative GML, as well as their potential response to bacterial eradication therapy.


Asunto(s)
Gastritis , Infecciones Intraabdominales , Linfoma de Células B de la Zona Marginal , Neoplasias Gástricas , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Gastritis/tratamiento farmacológico
5.
World J Gastroenterol ; 29(30): 4604-4615, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37662864

RESUMEN

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


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Enfermedades Inflamatorias del Intestino , Humanos , Infecciones por Helicobacter/complicaciones , Inmunidad Innata , Estómago
6.
World J Virol ; 12(3): 193-203, 2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37396702

RESUMEN

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major challenge to be faced in recent years. While adults suffered the highest morbidity and mortality rates of coronavirus disease 2019, children were thought to be exclusively asymptomatic or to present with mild conditions. However, around April 2020, there was an outbreak of a new clinical syndrome related to SARS-CoV-2 in children - multisystemic inflammatory syndrome in children (MIS-C) - which comprises a severe and uncon-trolled hyperinflammatory response with multiorgan involvement. The Centers for Disease Control and Prevention considers a suspected case of MIS-C an individual aged < 21 years presenting with fever, high inflammatory markers levels, and evidence of clinically severe illness, with multisystem (> 2) organ involvement, no alternative plausible diagnoses, and positive for recent SARS-CoV-2 infection. Despite its severity, there are no definitive disease management guidelines for this condition. Conversely, the complex pathogenesis of MIS-C is still not completely understood, although it seems to rely upon immune dysregulation. Hence, in this study, we aim to bring together current evidence regarding the pathogenic mechanisms of MIS-C, clinical picture and management, in order to provide insights for clinical practice and implications for future research directions.

7.
World J Biol Chem ; 14(4): 72-83, 2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37547340

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) has demonstrated several clinical manifestations which include not only respiratory system issues but also liver, kidney, and other organ injuries. One of these abnormalities is coagulopathies, including thrombosis and disseminated intravascular coagulation. Because of this, the administration of low molecular weight heparin is required for patients that need to be hospitalized. In addition, Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome, Ebola, Acute Respiratory Syndrome, and other diseases, showing satisfactory results on recovery. Besides, there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19. AIM: To investigate in silico the interaction between Remdesivir and clotting factors, pursuing a possibility of using it as medicine. METHODS: In this in silico study, the 3D structures of angiotensin-converting enzyme 2 (ACE2), Factor I (fibrinogen), Factor II (prothrombin), Factor III (thromboplastin), Factor V (proaccelerin), Factor VII (proconvertin), Factor VIII (antihemophilic factor A), Factor IX (antihemophilic factor B), Factor X (Stuart-Prower factor), and Factor XI (precursor of thromboplastin (these structures are technically called receptors) were selected from the Protein Data Bank. The structures of the antivirals Remdesivir and Osetalmivir (these structures are called ligands) were selected from the PubChem database, while the structure of Atazanavir was selected from the ZINC database. The software AutoDock Tools (ADT) was used to prepare the receptors for molecular docking. Ions, peptides, water molecules, and other ones were removed from each ligand, and then, hydrogen atoms were added to the structures. The grid box was delimited and calculated using the same software ADT. A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors, and still the software Marvin sketch® (ChemAxon®) was used to forecast the protonation state. To perform molecular docking, ADT and Vina software was connected. Using PyMol® software and Discovery studio® software from BIOVIA, it was possible to analyze the amino acid residues from receptors that were involved in the interactions with the ligands. Ligand tortions, atoms that participated in the interactions, and the type, strength, and duration of the interactions were also analyzed using those software. RESULTS: Molecular docking analysis showed that Remdesivir and ACE2 had an affinity energy of -8.8 kcal/moL, forming a complex with eight hydrogen bonds involving seven atoms of Remdesivir and five amino acid residues of ACE2. Remdesivir and prothrombin had an interaction with six hydrogen bonds involving atoms of the drug and five amino acid residues of the clotting factor. Similar to that, Remdesivir and thromboplastin presented interactions via seven hydrogen bonds involving five atoms of the drug and four residues of the clotting factor. While Remdesivir and Factor V established a complex with seven hydrogen bonds between six antiviral atoms and six amino acid residues from the factor, and Factor VII connected with the drug by four hydrogen bonds, which involved three atoms of the drug and three residues of amino acids of the factor. The complex between Remdesivir and Factor IX formed an interaction via 11 hydrophilic bonds with seven atoms of the drug and seven residues of the clotting factor, plus one electrostatic bond and three hydrophobic interactions. Factor X and Remdesivir had an affinity energy of -9.6 kcal/moL, and the complex presented 10 hydrogen bonds and 14 different hydrophobic interactions which involved nine atoms of the drug and 16 amino acid residues of the clotting factor. The interaction between Remdesivir and Factor XI formed five hydrogen bonds involving five amino acid residues of the clotting factor and five of the antiviral atoms. CONCLUSION: Because of the in silico significant affinity, Remdesivir possibly could act in the severe acute respiratory syndrome coronavirus 2 infection blockade by interacting with ACE2 and concomitantly act in the modulation of the coagulation cascade preventing the hypercoagulable state.

8.
World J Methodol ; 13(5): 399-413, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38229938

RESUMEN

Crohn's Disease (CD) is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature. Its etiology results from the interaction between genetic, enviromental and microbial factors. Regarding pathophysiology, it involves high levels of interleukin (IL)-12, IL-17, and Th1 profile, along with loss of tolerance mechanisms, an increase in pro-inflammatory interleukins, beyond the possibility to affect any part of the gastrointestinal tract. Its symptoms include abdominal pain, chronic diarrhea, weight loss, anorexia, and fatigue, as well as blood in the stool or rectum. Additionally, conditions comprising musculoskeletal, cutaneous, ocular, hepatic, and hematological alterations may be associated with this scenario and extra-intestinal presentation, such as erythema nodosum, anterior uveitis, osteoporosis, and arthritis can also occur. Today, clinical history, exams as fecal calprotectin, ileocolonocopy, and capsule endoscopy can be performed in the diagnosis investigation, along with treatments to induce and maintain remission. In this sense, anti-inflammatory drugs, such as corticosteroids, immunomodulators, and biological agents, as well as surgery and non-pharmacological interventions plays a role in its therapy. The aim of this review is to bring more current evidence to clinical management of CD, as well as to briefly discuss aspects of its pathophysiology, surveillance, and associated disorders.

10.
World J Gastroenterol ; 29(14): 2202-2221, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37122607

RESUMEN

BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori)-induced chronic gastritis. Clinical practice guidelines currently recommend H. pylori eradication as the preferred initial treatment for early-stage GML. To 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 imperative. AIM: To perform a meta-analysis to assess the rate of complete remission (CR) of H. pylori-positive early-stage GML following bacterial eradication. METHODS: We performed independent, computer-assisted literature searches using the PubMed/MEDLINE, Embase, and Cochrane Central databases through September 2022. Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H. pylori-positive patients. The risk of bias was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools. The pooled estimate of the complete histopathological remission rate and respective confidence intervals (95%CI) were calculated following the random-effects model. Heterogeneity and inconsistency were assessed using Cochran's Q test and I2 statistic, and heterogeneity was defined as P < 0.01 and I² > 50%, respectively. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. RESULTS: The titles and abstracts of 1576 studies were screened; 96 articles were retrieved and selected for full-text reading. Finally, 61 studies were included in the proportional meta-analysis (P-MA). Forty-six were prospective and fifteen were retrospective uncontrolled, single-arm, observational studies. The 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 H. pylori-positive early-stage GML patients, in whom H. pylori was successfully eradicated, were included in the analysis. The pooled CR of H. pylori-positive early-stage GML after bacterial eradication was 75.18% (95%CI: 70.45%-79.91%). P-MA indicated the substantial heterogeneity in CR reported across studies (I 2 = 92%; P < 0.01). Meta-regression analysis identified statistically significant effect modifiers, including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study. CONCLUSION: Comprehensive synthesis of available evidence suggests that H. pylori eradication is effective as the sole initial therapy for early-stage GML. Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR, the present study is a relevant to informing clinical practice.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Linfoma de Células B de la Zona Marginal , Neoplasias Gástricas , Humanos , Linfoma de Células B de la Zona Marginal/microbiología , Antibacterianos/farmacología , Estudios Retrospectivos , Estudios Prospectivos , Infecciones por Helicobacter/microbiología , Neoplasias Gástricas/patología
11.
World J Clin Oncol ; 14(4): 138-159, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37124134

RESUMEN

Glioblastoma remains as the most common and aggressive malignant brain tumor, standing with a poor prognosis and treatment prospective. Despite the aggressive standard care, such as surgical resection and chemoradiation, median survival rates are low. In this regard, immunotherapeutic strategies aim to become more attractive for glioblastoma, considering its recent advances and approaches. In this review, we provide an overview of the current status and progress in immunotherapy for glioblastoma, going through the fundamental knowledge on immune targeting to promising strategies, such as Chimeric antigen receptor T-Cell therapy, immune checkpoint inhibitors, cytokine-based treatment, oncolytic virus and vaccine-based techniques. At last, it is discussed innovative methods to overcome diverse challenges, and future perspectives in this area.

12.
World J Clin Cases ; 11(8): 1761-1770, 2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36970001

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a major health concern worldwide. In 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 remedy. AIM: To describe epidemiological features, signs, symptoms, and laboratory findings among severely ill COVID-19 patients from an intensive care unit in northeastern Brazil as well as to evaluate predictor factors for disease outcomes. METHODS: This is a prospective single-center study that evaluated 115 patients admitted to the intensive care unit in a northeastern Brazilian hospital. RESULTS: The patients had a median age of 65.60 ± 15.78 years. Dyspnea 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 patients. At 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 death. Nausea and vomiting were two symptoms that were predictors of death, and the presence of a cough was a protective factor. CONCLUSION: This is the first report of a negative correlation between cough and death in severely ill severe acute respiratory syndrome coronavirus 2-infected individuals. The 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.

13.
World J Gastrointest Endosc ; 14(5): 311-319, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35719896

RESUMEN

BACKGROUND: Esophagitis is an inflammatory and damaging process of the esophageal mucosa, which is confirmed by endoscopic visualization and may, in extreme cases, result in stenosis, fistulization and esophageal perforation. The use of deep learning (a field of artificial intelligence) techniques can be considered to determine the presence of esophageal lesions compatible with esophagitis. AIM: To develop, using transfer learning, a deep neural network model to recognize the presence of esophagitis in endoscopic images. METHODS: Endoscopic images of 1932 patients with a diagnosis of esophagitis and 1663 patients without any pathological diagnosis provenient from the KSAVIR and HyperKSAVIR datasets were splitted in training (80%) and test (20%) and used to develop and evaluate a binary deep learning classifier built using the DenseNet-201 architecture, a densely connected convolutional network, with weights pretrained on the ImageNet image set and fine-tuned during training. The classifier model performance was evaluated in the test set according to accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS: The model was trained using Adam optimizer with a learning rate of 0.0001 and applying binary cross entropy loss function. In the test set (n = 719), the classifier achieved 93.32% accuracy, 93.18% sensitivity, 93.46% specificity and a 0.96 AUC. Heatmaps for spatial predictive relevance in esophagitis endoscopic images from the test set were also plotted. In face of the obtained results, the use of dense convolutional neural networks with pretrained and fine-tuned weights proves to be a good strategy for predictive modeling for esophagitis recognition in endoscopic images. In addition, adopting the classification approach combined with the subsequent plotting of heat maps associated with the classificatory decision gives greater explainability to the model. CONCLUSION: It is opportune to raise new studies involving transfer learning for the analysis of endoscopic images, aiming to improve, validate and disseminate its use for clinical practice.

14.
World J Clin Oncol ; 13(6): 496-504, 2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35949428

RESUMEN

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 leukemias. Because 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 MDM2. METHODS: For molecular docking simulations, the file containing structures of MDM2 (receptor) and the drug DS-3032B (ligand) were selected. The three-dimensional structure of MDM2 was obtained from Protein Data Bank, and the one for DS-3032B was obtained from PubChem database. The location and dimensions of the Grid box was determined using AutoDock Tools software. In this case, the dimensions of the Grid encompassed the entire receptor. The 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® software. Both ligands, with and without the protonation, were prepared for molecular docking using the AutoDock Tools software. This software detects the torsion points of the drug and calculates the angle of the torsions. Molecular docking simulations were performed using the tools of the AutoDock platform connected to the Vina software. The 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 (pymol.org/2) and Discovery Studio from BIOVIA®. RESULTS: The global alignment indicated crystal structure 5SWK was more suitable for docking simulations by presenting the p53 binding site. The three-dimensional structure 5SWK for MDM2 was selected from Protein Data Bank and the three-dimensional structure of DS-3032B was selected from PubChem (Compound CID: 73297272; Milademetan). After molecular docking simulations, the most stable conformer was selected for both protonated and non-protonated DS-3032B. The interaction between MDM2 and DS-3032B occurs with high affinity; no significant difference was observed in the affinity energies between the MDM2/pronated DS-3032B (-9.9 kcal/mol) and MDM2/non-protonated DS-3032B conformers (-10.0 kcal/mol). Sixteen amino acid residues of MDM2 are involved in chemical bonds with the protonated DS-3032B; these 16 residues of MDM2 belong to the p53 biding site region and provide high affinity to interaction and stability to drug-protein complex. CONCLUSION: Molecular docking indicated that DS-3032B antagonist binds to the same region of the p53 binding site in the MDM2 with high affinity and stability, and this suggests therapeutic efficiency.

15.
World J Crit Care Med ; 11(5): 317-329, 2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36160934

RESUMEN

BACKGROUND: Intensive care unit (ICU) patients demand continuous monitoring of several clinical and laboratory parameters that directly influence their medical progress and the staff's decision-making. Those data are vital in the assistance of these patients, being already used by several scoring systems. In this context, machine learning approaches have been used for medical predictions based on clinical data, which includes patient outcomes. AIM: To develop a binary classifier for the outcome of death in ICU patients based on clinical and laboratory parameters, a set formed by 1087 instances and 50 variables from ICU patients admitted to the emergency department was obtained in the "WiDS (Women in Data Science) Datathon 2020: ICU Mortality Prediction" dataset. METHODS: For categorical variables, frequencies and risk ratios were calculated. Numerical variables were computed as means and standard deviations and Mann-Whitney U tests were performed. We then divided the data into a training (80%) and test (20%) set. The training set was used to train a predictive model based on the Random Forest algorithm and the test set was used to evaluate the predictive effectiveness of the model. RESULTS: A statistically significant association was identified between need for intubation, as well predominant systemic cardiovascular involvement, and hospital death. A number of the numerical variables analyzed (for instance Glasgow Coma Score punctuations, mean arterial pressure, temperature, pH, and lactate, creatinine, albumin and bilirubin values) were also significantly associated with death outcome. The proposed binary Random Forest classifier obtained on the test set (n = 218) had an accuracy of 80.28%, sensitivity of 81.82%, specificity of 79.43%, positive predictive value of 73.26%, negative predictive value of 84.85%, F1 score of 0.74, and area under the curve score of 0.85. The predictive variables of the greatest importance were the maximum and minimum lactate values, adding up to a predictive importance of 15.54%. CONCLUSION: We demonstrated the efficacy of a Random Forest machine learning algorithm for handling clinical and laboratory data from patients under intensive monitoring. Therefore, we endorse the emerging notion that machine learning has great potential to provide us support to critically question existing methodologies, allowing improvements that reduce mortality.

16.
World J Clin Oncol ; 13(11): 866-879, 2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36483973

RESUMEN

Gastric cancer is the fifth most common malignancy and third leading cancer-related cause of death worldwide. Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3% of the world's population and represents the main risk factor for the onset of gastric neoplasms. CagA is the most important virulence factor in H. pylori, and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions. Upon translocation and tyrosine phosphorylation, CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways, thereby disrupting cell proliferation, differentiation and apoptosis. All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes. In this sense, once gastric cancer sets in, its perpetuation is independent of the presence of the oncoprotein, characterizing a "hit-and-run" carcinogenic mechanism. Therefore, this review aims to describe H. pylori- and CagA-related oncogenic mechanisms, to update readers and discuss the novelties and perspectives in this field.

17.
World J Clin Cases ; 10(31): 11283-11291, 2022 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-36387830

RESUMEN

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects about half of the world's population. H. pylori infection prevails by several mechanisms of adaptation of the bacteria and by its virulence factors including the cytotoxin associated antigen A (CagA). CagA is an oncoprotein that is the protagonist of gastric carcinogenesis associated with prolonged H. pylori infection. In this sense, small regulatory RNAs (sRNAs) are important macromolecules capable of inhibiting and activating gene expression. This function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial infections. Recent discoveries have shown that nickel-regulated small RNA (NikS) is a post-transcriptional regulator of virulence properties of H. pylori, including the oncoprotein CagA. Notably, high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of CagA. In addition, NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients without. With that in mind, this minireview approaches, in an accessible way, the most important and current aspects about the role of NikS in the control of virulence factors of H. pylori and the potential clinical repercussions of this modulation.

18.
World J Gastrointest Pathophysiol ; 13(5): 157-169, 2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36187602

RESUMEN

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) pandemic. The 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 patients. In that context, health authorities and organizations have elaborated new guidelines with specific recommendations for the management of individuals with gastrointestinal neoplasms during the pandemic. Of 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 patients. Moreover, 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 malignancies. In 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 SARS-CoV-2 infection in those individuals and the scenario of the vaccination against the virus in that population.

19.
World J Exp Med ; 12(5): 100-103, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36196438

RESUMEN

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 negative. However, 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.

20.
World J Methodol ; 12(5): 350-364, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36186746

RESUMEN

Although the coronavirus disease 2019 (COVID-19) pandemic has reached all over the world population, it has demonstrated a heterogeneous impact on different populations. The most vulnerable communities which coexist daily with the social inequalities like low access to hygiene and personal protection products, crowded residences, and higher levels of chronic diseases have a higher risk of contact and the spread of infection, beyond unfavorable clinical outcomes. The elevation of the risk of infection exposure can be related to gender due to the presence of a larger contingent of women in essential services, as well as frontline and cleaning professionals who regardless of gender have the greatest exposure to the virus. Such exposures can contribute to the development of fear of contaminating themselves or their family members associated also with the work stress, both of which are related to the emergence of mental disturbances in these populations. Furthermore, conditions of unsanitary living and low socioeconomic status, populations at war, pre-existing social barriers, and ethnicity have contributed to more impact of the pandemic both in the exposure to the virus and access to health services, COVID-19 management, and management of other pathologies. At the same time, factors such as the closing of non-essential services, the loss of jobs, and the increase in household spending aggravated the social vulnerabilities and impacted the family economy. Lastly, the COVID-19 pandemic contributed still more to the impact on women's health since it propitiated a favorable environment for increasing domestic violence rates, through the segregation of women from social life, and increasing the time of the victims with their aggressors.

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