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1.
Fetal Pediatr Pathol ; : 1-12, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106665

RESUMO

Introduction: Pediatric DLBCL is considered a homogenous group and has superior outcomes compared to adults. This study investigated the clinical pathology and immunohistochemical distinction between adult and pediatric large B-cell lymphoma. Methods: A cross-sectional study of 314 NHLs with the morphology of diffuse pattern, large B-cell, and CD20 expression was investigated. Results: Of 314 cases, there were 6 cases of pleomorphic MCL (all in adults), 19 cases of Burkitt lymphoma (all in children), and 289 cases of DLBCL. Pediatric DLBCL had many striking differences: More frequency in extra-nodal sites; a higher proportion of centroblastic morphology; a predominance of GCB-type; a high proliferation rate; an infrequency of Bcl2 protein expression, and a lack of double-expresser lymphoma. Conclusions: Our study demonstrated the significant biological differences between adult and pediatric DLBCL.

2.
Clin Immunol ; 237: 108980, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35296428

RESUMO

Neuropsychiatric systemic lupus erythematosus (NPSLE) varies in presentation and is one of the leading causes of morbidity and mortality among patients with SLE. This study determined the most critical serum biomarkers for the development of NPSLE as they may have clinical utility prior to the onset of neuropsychiatric symptoms. We retrospectively analyzed 35 NPSLE patients, 34 SLE patients, 20 viral meningitis (VM) patients, and 16 relapsing-remitting multiple sclerosis (MS) patients. We measured anti-suprabasin antibodies concentrations in serum by using Luciferase immunoprecipitation system (LIPS) assay. The serum concentrations of cytokines/chemokines were measured by using multiplex bead-based assay. We found serum FGF-2 level was significantly higher in the NPSLE group compared to the SLE group and the healthy control group. The anti-suprabasin antibody relative concentration (SRC) has high positive predictive values for the development of NPSLE. The most essential biomarkers are VEGF, anti-suprabasin antibodies, sCD40L, IL-10, GRO, MDC, IL-8, IL-9, TNF-α, MIP-1α.


Assuntos
Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Biomarcadores , Quimiocinas , Citocinas , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Estudos Retrospectivos
3.
J Chem Inf Model ; 62(21): 5080-5089, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-35157472

RESUMO

Cancer is one of the most deadly diseases that annually kills millions of people worldwide. The investigation on anticancer medicines has never ceased to seek better and more adaptive agents with fewer side effects. Besides chemically synthetic anticancer compounds, natural products are scientifically proved as a highly potential alternative source for anticancer drug discovery. Along with experimental approaches being used to find anticancer drug candidates, computational approaches have been developed to virtually screen for potential anticancer compounds. In this study, we construct an ensemble computational framework, called iANP-EC, using machine learning approaches incorporated with evolutionary computation. Four learning algorithms (k-NN, SVM, RF, and XGB) and four molecular representation schemes are used to build a set of classifiers, among which the top-four best-performing classifiers are selected to form an ensemble classifier. Particle swarm optimization (PSO) is used to optimise the weights used to combined the four top classifiers. The models are developed by a set of curated 997 compounds which are collected from the NPACT and CancerHSP databases. The results show that iANP-EC is a stable, robust, and effective framework that achieves an AUC-ROC value of 0.9193 and an AUC-PR value of 0.8366. The comparative analysis of molecular substructures between natural anticarcinogens and nonanticarcinogens partially unveils several key substructures that drive anticancerous activities. We also deploy the proposed ensemble model as an online web server with a user-friendly interface to support the research community in identifying natural products with anticancer activities.


Assuntos
Antineoplásicos , Produtos Biológicos , Humanos , Produtos Biológicos/farmacologia , Algoritmos , Aprendizado de Máquina , Bases de Dados Factuais , Antineoplásicos/farmacologia
4.
Int J Biol Macromol ; 206: 203-212, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35183603

RESUMO

A novel bifunctional ß-lactamase/esterase (LgLacI), which is capable of hydrolyzing ß-lactam-containing antibiotics including ampicillin, oxacillin, and cefotaxime as well as synthesizing biodiesels, was cloned from Lactococcus garvieae. Unlike most bacterial esterases/lipases that have G-x-S-x-G motif, LgLacI, which contains S-x-x-K catalytic motif, has sequence similarities to bacterial family VIII esterase as well as ß-lactamases. The catalytic properties of LgLacI were explored using a wide range of biochemical methods including spectroscopy, assays, structural modeling, mutagenesis, and chromatography. We confirmed the bifunctional property of LgLacI hydrolyzing both esters and ß-lactam antibiotics. This study provides novel perspectives into a bifunctional enzyme from L. garvieae, which can degrade ß-lactam antibiotics with high esterase activity.


Assuntos
Esterases , beta-Lactamases , Sequência de Aminoácidos , Antibacterianos/farmacologia , Cefotaxima , Esterases/química , Lactococcus , beta-Lactamases/química
5.
J Med Internet Res ; 24(2): e33062, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35195534

RESUMO

BACKGROUND: Nonadherence to medication in tuberculosis (TB) hampers optimal treatment outcomes. Digital health technology (DHT) seems to be a promising approach to managing problems of nonadherence to medication and improving treatment outcomes. OBJECTIVE: This paper systematically reviews the effect of DHT in improving medication adherence and treatment outcomes in patients with TB. METHODS: A literature search in PubMed and Cochrane databases was conducted. Randomized controlled trials (RCTs) that analyzed the effect of DHT interventions on medication adherence outcomes (treatment completion, treatment adherence, missed doses, and noncompleted rate) and treatment outcomes (cure rate and smear conversion) were included. Adult patients with either active or latent TB infection were included. The Jadad score was used for evaluating the study quality. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed to report study findings. RESULTS: In all, 16 RCTs were selected from 552 studies found, and 6 types of DHT interventions for TB were identified: 3 RCTs examined video directly observed therapy (VDOT), 1 examined video-observed therapy (VOT), 1 examined an ingestible sensor, 1 examined phone call reminders, 2 examined medication monitor boxes, and 8 examined SMS text message reminders. The outcomes used were treatment adherence, including treatment completion, treatment adherence, missed dose, and noncompleted rate, as well as clinical outcomes, including cure rate and smear conversion. In treatment completion, 4 RCTs (VDOT, VOT, ingestible sensor, SMS reminder) found significant effects, with odds ratios and relative risks (RRs) ranging from 1.10 to 7.69. Treatment adherence was increased in 1 study by SMS reminders (RR 1.05; 95% CI 1.04-1.06), and missed dose was reduced in 1 study by a medication monitor box (mean ratio 0.58; 95% CI 0.42-0.79). In contrast, 3 RCTs of VDOT and 3 RCTs of SMS reminders did not find significant effects for treatment completion. Moreover, no improvement was found in treatment adherence in 1 RCT of VDOT, missed dose in 1 RCT of SMS reminder, and noncompleted rate in 1 RCT of a monitor box, and 2 RCTs of SMS reminders. For clinical outcomes such as cure rate, 2 RCTs reported that phone calls (RR 1.30; 95% CI 1.07-1.59) and SMS reminders (OR 2.47; 95% CI 1.13-5.43) significantly affected cure rates. However, 3 RCTs found that SMS reminders did not have a significant impact on cure rate or smear conversion. CONCLUSIONS: It was found that DHT interventions can be a promising approach. However, the interventions exhibited variable effects regarding effect direction and the extent of improving TB medication adherence and clinical outcomes. Developing DHT interventions with personalized feedback is required to have a consistent and beneficial effect on medication adherence and outcomes among patients with TB.


Assuntos
Telefone Celular , Envio de Mensagens de Texto , Tuberculose , Adulto , Tecnologia Biomédica , Humanos , Adesão à Medicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistemas de Alerta , Resultado do Tratamento
7.
J Chem Inf Model ; 62(21): 5059-5068, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-34672553

RESUMO

The human cytochrome P450 (CYP) superfamily holds responsibilities for the metabolism of both endogenous and exogenous compounds such as drugs, cellular metabolites, and toxins. The inhibition exerted on the CYP enzymes is closely associated with adverse drug reactions encompassing metabolic failures and induced side effects. In modern drug discovery, identification of potential CYP inhibitors is, therefore, highly essential. Alongside experimental approaches, numerous computational models have been proposed to address this biochemical issue. In this study, we introduce iCYP-MFE, a computational framework for virtual screening on CYP inhibitors toward 1A2, 2C9, 2C19, 2D6, and 3A4 isoforms. iCYP-MFE contains a set of five robust, stable, and effective prediction models developed using multitask learning incorporated with molecular fingerprint-embedded features. The results show that multitask learning can remarkably leverage useful information from related tasks to promote global performance. Comparative analysis indicates that iCYP-MFE achieves three predominant tasks, one equivalent task, and one less effective task compared to state-of-the-art methods. The area under the receiver operating characteristic curve (AUC-ROC) and the area under the precision-recall curve (AUC-PR) were two decisive metrics used for model evaluation. The prediction task for CYP2D6-inhibition achieves the highest AUC-ROC value of 0.93 while the prediction task for CYP1A2-inhibition obtains the highest AUC-PR value of 0.92. The substructural analysis preliminarily explains the nature of the CYP-inhibitory activity of compounds. An online web server for iCYP-MFE with a user-friendly interface was also deployed to support scientific communities in identifying CYP inhibitors.


Assuntos
Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450 , Humanos , Inibidores das Enzimas do Citocromo P-450/farmacologia , Inibidores das Enzimas do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Citocromo P-450 CYP2D6 , Área Sob a Curva , Microssomos Hepáticos/metabolismo
8.
Front Med (Lausanne) ; 9: 1065045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36714104

RESUMO

Helicobacter pylori (H. pylori) infection is prevalent and has a rapidly increasing antibiotic resistance rate in Vietnam. Reinfection is quite common, and gastric carcinoma remains one of the most common malignancies, which is not uncommon to develop after successful eradication. The purpose of this consensus is to provide updated recommendations on the management of H. pylori infection in the country. The consensus panel consisted of 32 experts from 14 major universities and institutions in Vietnam who were invited to review the evidence and develop the statements using the Delphi method. The process followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The consensus level was defined as ≥80% for agreement on the proposed statements. Due to the limited availability of high-quality local evidence, this consensus was also based on high-quality evidence from international studies, especially those conducted in other populations in the Asia-Pacific region. The panel finally reached a consensus on 27 statements after two voting rounds, which consisted of four sections (1) indications for testing and selection of diagnostic tests (2), treatment regimens, (3) post-treatment confirmation of H. pylori status, and (4) reinfection prevention methods and follow-up after eradication. Important issues that require further evidence include studies on third-line regimens, strategies to prevent H. pylori reinfection, and post-eradication follow-up for precancerous gastric lesions. We hope this consensus will help guide the current clinical practice in Vietnam and promote multicenter studies in the country and international collaborations.

9.
Evol Bioinform Online ; 17: 11769343211003082, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33795930

RESUMO

A high level of mutation enables the influenza A virus to resist antibiotics previously effective against the influenza A virus. A portion of the structure of hemagglutinin HA is assumed to be well-conserved to maintain its role in cellular fusion, and the structure tends to be more conserved than sequence. We designed peptide inhibitors to target the conserved residues on the HA surface, which were identified based on structural alignment. Most of the conserved and strongly similar residues are located in the receptor-binding and esterase regions on the HA1 domain In a later step, fragments of anti-HA antibodies were gathered and screened for the binding ability to the found conserved residues. As a result, Methionine amino acid got the best docking score within the -2.8 Å radius of Van der Waals when it is interacting with Tyrosine, Arginine, and Glutamic acid. Then, the binding affinity and spectrum of the fragments were enhanced by grafting hotspot amino acid into the fragments to form peptide inhibitors. Our peptide inhibitor was able to form in silico contact with a structurally conserved region across H1, H2, and H3 HA, with the binding site at the boundary between HA1 and HA2 domains, spreading across different monomers, suggesting a new target for designing broad-spectrum antibody and vaccine. This research presents an affordable method to design broad-spectrum peptide inhibitors using fragments of an antibody as a scaffold.

10.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33673022

RESUMO

Grain legumes are important crops, but they are salt sensitive. This research dissected the responses of four (sub)tropical grain legumes to ionic components (Na+ and/or Cl-) of salt stress. Soybean, mungbean, cowpea, and common bean were subjected to NaCl, Na+ salts (without Cl-), Cl- salts (without Na+), and a "high cation" negative control for 57 days. Growth, leaf gas exchange, and tissue ion concentrations were assessed at different growing stages. For soybean, NaCl and Na+ salts impaired seed dry mass (30% of control), more so than Cl- salts (60% of control). All treatments impaired mungbean growth, with NaCl and Cl- salt treatments affecting seed dry mass the most (2% of control). For cowpea, NaCl had the greatest adverse impact on seed dry mass (20% of control), while Na+ salts and Cl- salts had similar intermediate effects (~45% of control). For common bean, NaCl had the greatest adverse effect on seed dry mass (4% of control), while Na+ salts and Cl- salts impaired seed dry mass to a lesser extent (~45% of control). NaCl and Na+ salts (without Cl-) affected the photosynthesis (Pn) of soybean more than Cl- salts (without Na+) (50% of control), while the reverse was true for mungbean. Na+ salts (without Cl-), Cl- salts (without Na+), and NaCl had similar adverse effects on Pn of cowpea and common bean (~70% of control). In conclusion, salt sensitivity is predominantly determined by Na+ toxicity in soybean, Cl- toxicity in mungbean, and both Na+ and Cl- toxicity in cowpea and common bean.


Assuntos
Cloretos/toxicidade , Phaseolus/efeitos dos fármacos , Cloreto de Sódio/toxicidade , Sódio/toxicidade , Soja/efeitos dos fármacos , Vigna/efeitos dos fármacos , Biomassa , Phaseolus/crescimento & desenvolvimento , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Tolerância ao Sal/efeitos dos fármacos , Soja/crescimento & desenvolvimento , Especificidade da Espécie , Vigna/classificação , Vigna/crescimento & desenvolvimento
11.
Hum Genome Var ; 8(1): 7, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542200

RESUMO

Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.

12.
Gastroenterol Res Pract ; 2021: 8674367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505461

RESUMO

AIMS: This study is aimed at (1) validating the performance of Oakland and Glasgow-Blatchford (GBS) scores and (2) comparing these scores with the SALGIB score in predicting adverse outcomes of acute lower gastrointestinal bleeding (ALGIB) in a Vietnamese population. METHODS: A multicenter cohort study was conducted on ALGIB patients admitted to seven hospitals across Vietnam. The adverse outcomes of ALGIB consisted of blood transfusion; endoscopic, radiologic, or surgical interventions; severe bleeding; and in-hospital death. The Oakland and GBS scores were calculated, and their performance was compared with that of SALGIB, a locally developed prediction score for adverse outcomes of ALGIB in Vietnamese, based on the data at admission. The accuracy of these scores was measured using the area under the receiver operating characteristic curve (AUC) and compared by the chi-squared test. RESULTS: There were 414 patients with a median age of 60 (48-71). The rates of blood transfusion, hemostatic intervention, severe bleeding, and in-hospital death were 26.8%, 15.2%, 16.4, and 1.4%, respectively. The SALGIB score had comparable performance with the Oakland score (AUC: 0.81 and 0.81, respectively; p = 0.631) and outperformed the GBS score (AUC: 0.81 and 0.76, respectively; p = 0.002) for predicting the presence of any adverse outcomes of ALGIB. All of the three scores had acceptable and comparable performance for in-hospital death but poor performance for hemostatic intervention. The Oakland score had the best performance for predicting severe bleeding. CONCLUSIONS: The Oakland and SALGIB scores had excellent and comparable performance and outperformed the GBS score for predicting adverse outcomes of ALGIB in Vietnamese.

13.
Pharmgenomics Pers Med ; 14: 61-75, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33469342

RESUMO

Pharmacogenomics has been used effectively in studying adverse drug reactions by determining the person-specific genetic factors associated with individual response to a drug. Current approaches have revealed the significant importance of sequencing technologies and sequence analysis strategies for interpreting the contribution of genetic variation in developing adverse reactions. Advance in next generation sequencing and platform brings new opportunities in validating the genetic candidates in certain reactions, and could be used to develop the preemptive tests to predict the outcome of the variation in a personal response to a drug. With the highly accumulated available data recently, the in silico approach with data analysis and modeling plays as other important alternatives which significantly support the final decisions in the transformation from research to clinical applications such as diagnosis and treatments for various types of adverse responses.

14.
Cells ; 10(9)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34572142

RESUMO

Cellular stress induces the formation of membraneless protein condensates in both the nucleus and cytoplasm. The nucleocytoplasmic transport of proteins mainly occurs through nuclear pore complexes (NPCs), whose efficiency is affected by various stress conditions. Here, we report that hyperosmotic stress compartmentalizes nuclear 26S proteasomes into dense nuclear foci, independent of signaling cascades. Most of the proteasome foci were detected between the condensed chromatin mass and inner nuclear membrane. The proteasome-positive puncta were not colocalized with other types of nuclear bodies and were reversibly dispersed when cells were returned to the isotonic medium. The structural integrity of 26S proteasomes in the nucleus was slightly affected under the hyperosmotic condition. We also found that these insulator-body-like proteasome foci were possibly formed through disrupted nucleus-to-cytosol transport, which was mediated by the sequestration of NPC components into osmostress-responding stress granules. These data suggest that phase separation in both the nucleus and cytosol may be a major cell survival mechanism during hyperosmotic stress conditions.


Assuntos
Poro Nuclear/metabolismo , Pressão Osmótica/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Cromatina , Citoplasma/metabolismo , Humanos , Membrana Nuclear/metabolismo , Complexo de Endopeptidases do Proteassoma/fisiologia , Agregados Proteicos/fisiologia , Proteínas/metabolismo , Estresse Fisiológico/fisiologia
15.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34615730

RESUMO

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the attachment of the receptor-binding domain (RBD) of its spike proteins to the ACE2 receptors on the peripheral membrane of host cells. Binding is initiated by a down-to-up conformational change in the spike protein, the change that presents the RBD to the receptor. To date, computational and experimental studies that search for therapeutics have concentrated, for good reason, on the RBD. However, the RBD region is highly prone to mutations, and is therefore a hotspot for drug resistance. In contrast, we here focus on the correlations between the RBD and residues distant to it in the spike protein. This allows for a deeper understanding of the underlying molecular recognition events and prediction of the highest-effect key mutations in distant, allosteric sites, with implications for therapeutics. Also, these sites can appear in emerging mutants with possibly higher transmissibility and virulence, and preidentifying them can give clues for designing pan-coronavirus vaccines against future outbreaks. Our model, based on time-lagged independent component analysis (tICA) and protein graph connectivity network, is able to identify multiple residues that exhibit long-distance coupling with the RBD opening. Residues involved in the most ubiquitous D614G mutation and the A570D mutation of the highly contagious UK SARS-CoV-2 variant are predicted ab initio from our model. Conversely, broad-spectrum therapeutics like drugs and monoclonal antibodies can target these key distant-but-conserved regions of the spike protein.


Assuntos
COVID-19/virologia , Modelos Químicos , SARS-CoV-2/química , Glicoproteína da Espícula de Coronavírus/química , Humanos , Terapia de Alvo Molecular , Conformação Proteica , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
16.
Dig Dis Sci ; 66(3): 823-831, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32285322

RESUMO

BACKGROUND/AIMS: The prevalence of acute lower gastrointestinal bleeding (ALGIB) has progressively increased worldwide but there are few studies in Asian populations. This study aimed to develop and validate a scoring system to predict severe ALGIB in Vietnamese. METHODS: Risk factors for severe ALGIB were identified by multiple logistic regression analysis using data from a retrospective cohort of 357 patients admitted to a tertiary hospital. These factors were weighted to develop the severe acute lower gastrointestinal bleeding (SALGIB) score to predict severe ALGIB. The performance of SALGIB was validated in a prospective cohort of 324 patients admitted to 6 other hospitals using area under the receiver operating characteristics curve (AUC) analysis. RESULTS: There were four factors at admission independently associated with severe ALGIB in the derivation cohort: heart rate ≥ 100/min, systolic blood pressure < 100 mmHg, hematocrit < 35%, and platelets ≤ 150 × 103/µL. The SALGIB score determined severe ALGIB with AUC values of 0.91 and 0.86 in the derivation and validation cohorts, respectively. A SALGIB score < 2 associated with low risk of severe ALGIB in both cohorts (3.7% and 1.2%; respectively). CONCLUSIONS: The SALGIB score has good performance in discriminating risk of severe ALGIB in Vietnamese.


Assuntos
/estatística & dados numéricos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etnologia , Medição de Risco/normas , Avaliação de Sintomas/normas , Doença Aguda , Idoso , Área Sob a Curva , Pressão Sanguínea , Feminino , Hemorragia Gastrointestinal/etiologia , Frequência Cardíaca , Hematócrito , Humanos , Modelos Logísticos , Trato Gastrointestinal Inferior , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Avaliação de Sintomas/métodos , Vietnã/etnologia
17.
PLoS One ; 15(12): e0239112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382708

RESUMO

Influenza virus A is a significant agent involved in the outbreak of worldwide epidemics, causing millions of fatalities around the world by respiratory diseases and seasonal illness. Many projects had been conducting to investigate recovered infected patients for therapeutic vaccines that have broad-spectrum activity. With the aid of the computational approach in biology, the designation for a vaccine model is more accessible. We developed an in silico protocol called iBRAB to design a broad-reactive Fab on a wide range of influenza A virus. The Fab model was constructed based on sequences and structures of available broad-spectrum Abs or Fabs against a wide range of H1N1 influenza A virus. As a result, the proposed Fab model followed iBRAB has good binding affinity over 27 selected HA of different strains of H1 influenza A virus, including wild-type and mutated ones. The examination also took by computational tools to fasten the procedure. This protocol could be applied for a fast-designed therapeutic vaccine against different types of threats.


Assuntos
Anticorpos Antivirais/química , Antígenos Virais/química , Desenho de Fármacos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Fragmentos Fab das Imunoglobulinas/química , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/prevenção & controle , Sequência de Aminoácidos , Anticorpos Antivirais/genética , Antígenos Virais/genética , Antígenos Virais/imunologia , Sítios de Ligação , Simulação por Computador , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Fragmentos Fab das Imunoglobulinas/genética , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/biossíntese , Influenza Humana/imunologia , Influenza Humana/virologia , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Termodinâmica
18.
HIV AIDS (Auckl) ; 12: 779-787, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262660

RESUMO

BACKGROUND: Management of HIV-infected children on a long-term basis is a challenge in resource-limited countries. The aim of this study is to evaluate the long-term outcome and identify the risk factors for mortality in a cohort of children with antiretroviral therapy (ART) in Vietnam. PATIENTS AND METHODS: A retrospective cohort study was conducted in children aged 0-15 years, seen at the outpatient clinic of the Women and Children Hospital of An Giang, Vietnam, from August 2006 to May 2019. Cox proportional-hazard models were used to determine factors associated with mortality. RESULTS: A total of 266 HIV-infected children were on ART. During 1545 child-years of follow-up (median follow-up was 5.8 years), 28 (10.5%) children died yielding a mortality rate of 1.8 death per 100 child-years. By multivariate analysis, World Health Organization clinical stage 3 or 4 (AHR; 7.86, 95% CI; 1.02-60.3, P= 0.047), tuberculosis (TB) co-infection (AHR; 6.26, 95% CI; 2.50-15.64, P= 0.001) and having severe immunosuppression before ART (AHR; 11.73, 95% CI; 1.52-90.4, P= 0.018) were independent factors for mortality in these children. CONCLUSION: Antiretroviral therapy has reduced mortality in HIV-infected children in resource-limited settings. Independent risk factors for mortality were advanced clinical stage (3 or 4), TB co-infection and severe immunosuppression. Early investigation and treatment of TB co-infection allow early ART initiation which may improve outcomes in our settings.

19.
ACS Omega ; 5(46): 30315-30322, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33251466

RESUMO

Coptis chinensis has been long used as the potential herbal remedy for the treatment of influenza A infection. The six isoquinolone alkaloids extracted from C. chinensis rhizomes are reported to have good inhibition activity on neuraminidase (NA) of Clostridium perfringens, A/H1N1/1918, and recombinant NA-1; however, the study of the effect of these candidates on other NAs of threatening influenza A causing pandemic and seasonal flu recently has not considered yet. The purpose of this study is to investigate the interaction between these compounds and NAs of different wild and mutant subtypes of influenza A. This process involved the molecular docking of 3D structures of those compounds (ligand) into target proteins NA of A/H1N1/1918, A/H1N1/2009pdm, H3N2/2010 wild type, H3N2/2010 D151G mutant, H5N1 wild type, and H5N1 H274Y mutant. Then, the Protein-Ligand Interaction Profiler (PLIP) was utilized to demonstrate the bond formed between the ligand and the binding pocket of receptors of interest. The results showed that six candidates including palmatine, berberine, jatrorrhizine, epiberberine, columbamine, and coptisine have a higher affinity to all six selected proteins than commercial drugs such as oseltamivir, zanamivir, and natural binding ligand sialic acid. The results could be explained via the 2D picture, which showed the hydrophobic interaction and hydrogen bonding forming between the oxygen molecules of the ligand with the free residue of proteins.

20.
ACS Omega ; 5(39): 25432-25439, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33043223

RESUMO

As a critical issue in drug development and postmarketing safety surveillance, drug-induced liver injury (DILI) leads to failures in clinical trials as well as retractions of on-market approved drugs. Therefore, it is important to identify DILI compounds in the early-stages through in silico and in vivo studies. It is difficult using conventional safety testing methods, since the predictive power of most of the existing frameworks is insufficiently effective to address this pharmacological issue. In our study, we employ a natural language processing (NLP) inspired computational framework using convolutional neural networks and molecular fingerprint-embedded features. Our development set and independent test set have 1597 and 322 compounds, respectively. These samples were collected from previous studies and matched with established chemical databases for structural validity. Our study comes up with an average accuracy of 0.89, Matthews's correlation coefficient (MCC) of 0.80, and an AUC of 0.96. Our results show a significant improvement in the AUC values compared to the recent best model with a boost of 6.67%, from 0.90 to 0.96. Also, based on our findings, molecular fingerprint-embedded featurizer is an effective molecular representation for future biological and biochemical studies besides the application of classic molecular fingerprints.

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