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J Biomed Semantics ; 12(1): 18, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454610


BACKGROUND: With COVID-19 still in its pandemic stage, extensive research has generated increasing amounts of data and knowledge. As many studies are published within a short span of time, we often lose an integrative and comprehensive picture of host-coronavirus interaction (HCI) mechanisms. As of early April 2021, the ImmPort database has stored 7 studies (with 6 having details) that cover topics including molecular immune signatures, epitopes, and sex differences in terms of mortality in COVID-19 patients. The Coronavirus Infectious Disease Ontology (CIDO) represents basic HCI information. We hypothesize that the CIDO can be used as the platform to represent newly recorded information from ImmPort leading the reinforcement of CIDO. METHODS: The CIDO was used as the semantic platform for logically modeling and representing newly identified knowledge reported in the 6 ImmPort studies. A recursive eXtensible Ontology Development (XOD) strategy was established to support the CIDO representation and enhancement. Secondary data analysis was also performed to analyze different aspects of the HCI from these ImmPort studies and other related literature reports. RESULTS: The topics covered by the 6 ImmPort papers were identified to overlap with existing CIDO representation. SARS-CoV-2 viral S protein related HCI knowledge was emphasized for CIDO modeling, including its binding with ACE2, mutations causing different variants, and epitope homology by comparison with other coronavirus S proteins. Different types of cytokine signatures were also identified and added to CIDO. Our secondary analysis of two cohort COVID-19 studies with cytokine panel detection found that a total of 11 cytokines were up-regulated in female patients after infection and 8 cytokines in male patients. These sex-specific gene responses were newly modeled and represented in CIDO. A new DL query was generated to demonstrate the benefits of such integrative ontology representation. Furthermore, IL-10 signaling pathway was found to be statistically significant for both male patients and female patients. CONCLUSION: Using the recursive XOD strategy, six new ImmPort COVID-19 studies were systematically reviewed, the results were modeled and represented in CIDO, leading to the enhancement of CIDO. The enhanced ontology and further seconary analysis supported more comprehensive understanding of the molecular mechanism of host responses to COVID-19 infection.

Ontologias Biológicas , COVID-19 , Interações entre Hospedeiro e Microrganismos , Humanos , Semântica , Glicoproteína da Espícula de Coronavírus/metabolismo
Front Immunol ; 12: 639491, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777032


Vaccines stimulate various immune factors critical to protective immune responses. However, a comprehensive picture of vaccine-induced immune factors and pathways have not been systematically collected and analyzed. To address this issue, we developed VaximmutorDB, a web-based database system of vaccine immune factors (abbreviated as "vaximmutors") manually curated from peer-reviewed articles. VaximmutorDB currently stores 1,740 vaccine immune factors from 13 host species (e.g., human, mouse, and pig). These vaximmutors were induced by 154 vaccines for 46 pathogens. Top 10 vaximmutors include three antibodies (IgG, IgG2a and IgG1), Th1 immune factors (IFN-γ and IL-2), Th2 immune factors (IL-4 and IL-6), TNF-α, CASP-1, and TLR8. Many enriched host processes (e.g., stimulatory C-type lectin receptor signaling pathway, SRP-dependent cotranslational protein targeting to membrane) and cellular components (e.g., extracellular exosome, nucleoplasm) by all the vaximmutors were identified. Using influenza as a model, live attenuated and killed inactivated influenza vaccines stimulate many shared pathways such as signaling of many interleukins (including IL-1, IL-4, IL-6, IL-13, IL-20, and IL-27), interferon signaling, MARK1 activation, and neutrophil degranulation. However, they also present their unique response patterns. While live attenuated influenza vaccine FluMist induced significant signal transduction responses, killed inactivated influenza vaccine Fluarix induced significant metabolism of protein responses. Two different Yellow Fever vaccine (YF-Vax) studies resulted in overlapping gene lists; however, they shared more portions of pathways than gene lists. Interestingly, live attenuated YF-Vax simulates significant metabolism of protein responses, which was similar to the pattern induced by killed inactivated Fluarix. A user-friendly web interface was generated to access, browse and search the VaximmutorDB database information. As the first web-based database of vaccine immune factors, VaximmutorDB provides systematical collection, standardization, storage, and analysis of experimentally verified vaccine immune factors, supporting better understanding of protective vaccine immunity.

Anticorpos Antivirais/imunologia , Imunidade/imunologia , Fatores Imunológicos/imunologia , Vacinas/imunologia , Animais , Bases de Dados Factuais , Humanos , Internet , Transdução de Sinais/imunologia , Vacinação/métodos
J Calif Dent Assoc ; 33(12): 951-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16454238


UNLABELLED: Tooth movement results from alveolar bone resorption/deposition following application of orthodontic forces, and root resorption can be an undesirable complication associated with this process. No treatment for external root resorption is available to date. OBJECTIVE: To determine if COX-2 inhibitors like Celebrex are effective in protecting root resorption associated with orthodontic forces. METHODS: A force of 80 grams was applied to the left maxillary first molars of 7-week-old female Wistar rats using nickel titanium closed coil springs attached to the cervical area of the incisors with 0.010 stainless-steel ligature wires. Twenty animals were divided into three experimental groups: one receiving no treatment, the second receiving 25mg/kg, and the third receiving 50 mg/kg of celecoxib (Celebrex) in their drinking water. Rats were maintained on a soft diet and euthanized two weeks after initial placement of the force. Paraffin-embedded sections of the right (control) and left (experimental) maxillae were stained with H&E and the areas of root resorption were examined by counting the number of lacunaes in the roots. RESULTS: No difference in the distance of tooth movement (0.5 mm/two weeks) was seen in all three groups. The rats that received the low dose of Celebrex showed no statistically significant difference in root resorption than that of the rats that received no dose. The rats that received the high dose of Celebrex showed a lower number of lacunaes (mean = 3.5) than that of the control group (mean 10.2; p=0.02). CONCLUSIONS: Administration of Celebrex during the application of orthodontic forces does not interfere with tooth movement and appears to offer some slight protection against root resorption.

Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Pirazóis/uso terapêutico , Reabsorção da Raiz/prevenção & controle , Sulfonamidas/uso terapêutico , Técnicas de Movimentação Dentária/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Celecoxib , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Ligas Dentárias , Feminino , Dente Molar , Níquel , Fios Ortodônticos , Pirazóis/administração & dosagem , Ratos , Ratos Wistar , Reabsorção da Raiz/patologia , Estresse Mecânico , Sulfonamidas/administração & dosagem , Titânio , Ápice Dentário/patologia , Colo do Dente/patologia , Técnicas de Movimentação Dentária/instrumentação