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2.
San Salvador; MINSAL; jun. 04, 2021. 11 p. ilus, graf, tab, mapas.
Não convencional em Espanhol | LILACS, BISSAL | ID: biblio-1248116

RESUMO

Resumen de eventos de notificación hasta SE 20/2021. Alertas internacionales. Situación epidemiológica de dengue. Situación epidemiológica de zika y chikungunya. Infección respiratoria aguda. Neumonías. Situación mundial del 2019-nCov (OMS. Vigilancia centinela de influenza y otros virus respiratorios. Vigilancia centinela de rotavirus. Enfermedad diarreica aguda. Fiebre tifoidea


Summary of notification events up to SE 20/2021. International alerts. Epidemiological situation of dengue. Epidemiological situation of Zika and Chikungunya. Acute respiratory infection. Pneumonia Global situation 2019-nCov (WHO. Sentinel surveillance of influenza and other respiratory viruses. Sentinel surveillance for rotavirus. Acute diarrheal disease. Typhoid fever


Assuntos
Epidemiologia , Notificação , Publicações Eletrônicas , Doença , Alerta
3.
Anal Chim Acta ; 1164: 338321, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992219

RESUMO

In the past several decades, acoustic wave biosensors, as an emerging kind of biosensors, have been developed and widely used for the detection of mass, viscosity, conductivity and density. Varieties of applications have been explored such as medical diagnosis, drug screening, environmental monitoring, food analysis and biochemical assay. Among them, the detection of disease-related biomarkers based on acoustic sensors has aroused great research interest all over the world. In this review, the classification and characteristics of acoustic wave biosensors are briefly introduced. Then, some classical studies and recent advances in disease-related biomarker detection utilizing these biosensors are summarized and detailed, respectively. Here, the disease-related biomarkers mainly include antigens, small molecular proteins, cancer cells, viruses and VOCs. Finally, challenges and future trends of these typical acoustic wave biosensors are discussed. Compared with other reviews of acoustic wave sensors, this review highlights the great potential of typical acoustic wave biosensors for early disease screening and diagnosis compared with widely-used medical imaging. Moreover, they are integrated with other technologies for the design of multi-analyte, multi-parameter and intelligent devices, collecting more comprehensive information from biomarkers. This review provides a new perspective on the applications and optimization of acoustic wave biosensors to develop more reliable platforms for disease-related biomarker detection and disease diagnosis.


Assuntos
Técnicas Biossensoriais , Doença , Acústica , Biomarcadores , Diagnóstico , Humanos , Proteínas , Som
4.
Nat Commun ; 12(1): 3008, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021151

RESUMO

Study of human disease remains challenging due to convoluted disease etiologies and complex molecular mechanisms at genetic, genomic, and proteomic levels. Many machine learning-based methods have been developed and widely used to alleviate some analytic challenges in complex human disease studies. While enjoying the modeling flexibility and robustness, these model frameworks suffer from non-transparency and difficulty in interpreting each individual feature due to their sophisticated algorithms. However, identifying important biomarkers is a critical pursuit towards assisting researchers to establish novel hypotheses regarding prevention, diagnosis and treatment of complex human diseases. Herein, we propose a Permutation-based Feature Importance Test (PermFIT) for estimating and testing the feature importance, and for assisting interpretation of individual feature in complex frameworks, including deep neural networks, random forests, and support vector machines. PermFIT (available at https://github.com/SkadiEye/deepTL ) is implemented in a computationally efficient manner, without model refitting. We conduct extensive numerical studies under various scenarios, and show that PermFIT not only yields valid statistical inference, but also improves the prediction accuracy of machine learning models. With the application to the Cancer Genome Atlas kidney tumor data and the HITChip atlas data, PermFIT demonstrates its practical usage in identifying important biomarkers and boosting model prediction performance.


Assuntos
Biomarcadores , Doença/genética , Aprendizado de Máquina , Algoritmos , Humanos , Neoplasias/genética , Redes Neurais de Computação , Proteômica , Máquina de Vetores de Suporte
5.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33924772

RESUMO

Wnt signaling is an important pathway mainly active during embryonic development and controlling cell proliferation. This regulatory pathway is aberrantly activated in several human diseases. Ion channels are known modulators of several important cellular functions ranging from the tuning of the membrane potential to modulation of intracellular pathways, in particular the influence of ion channels in Wnt signaling regulation has been widely investigated. This review will discuss the known links between ion channels and canonical Wnt signaling, focusing on their possible roles in human metabolic diseases, neurological disorders, and cancer.


Assuntos
Doença/etiologia , Canais Iônicos/metabolismo , Via de Sinalização Wnt , Animais , Humanos
6.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33924849

RESUMO

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.


Assuntos
Doença/etiologia , Dinâmica Mitocondrial , Animais , Humanos
7.
Molecules ; 26(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919699

RESUMO

RNA splicing is an essential step in producing mature messenger RNA (mRNA) and other RNA species. Harnessing RNA splicing modifiers as a new pharmacological modality is promising for the treatment of diseases caused by aberrant splicing. This drug modality can be used for infectious diseases by disrupting the splicing of essential pathogenic genes. Several antisense oligonucleotide splicing modifiers were approved by the U.S. Food and Drug Administration (FDA) for the treatment of spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD). Recently, a small-molecule splicing modifier, risdiplam, was also approved for the treatment of SMA, highlighting small molecules as important warheads in the arsenal for regulating RNA splicing. The cellular targets of these approved drugs are all mRNA precursors (pre-mRNAs) in human cells. The development of novel RNA-targeting splicing modifiers can not only expand the scope of drug targets to include many previously considered "undruggable" genes but also enrich the chemical-genetic toolbox for basic biomedical research. In this review, we summarized known splicing modifiers, screening methods for novel splicing modifiers, and the chemical space occupied by the small-molecule splicing modifiers.


Assuntos
Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Splicing de RNA/genética , Animais , Sequência de Bases , Doença/genética , Humanos , Bibliotecas de Moléculas Pequenas/farmacologia , Spliceossomos/metabolismo
8.
Health Qual Life Outcomes ; 19(1): 113, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820569

RESUMO

The objective is to present and share an Excel program that we have developed to perform statistical analyses based on the Improved RIDIT approach of Marfak et al.'s article 'Improved RIDIT statistic approach provides more intuitive and informative interpretation of EQ-5D Data'.


Assuntos
Interpretação Estatística de Dados , Doença , Nível de Saúde , Qualidade de Vida , Software , Inquéritos e Questionários/normas , Terapêutica/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Nutrients ; 13(4)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918657

RESUMO

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl--dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4-]2- and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3-]-. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.


Assuntos
Biologia Computacional , Creatina/metabolismo , Doença , Saúde , Animais , Transporte Biológico , Creatina/biossíntese , Creatina/química , Creatina Quinase/metabolismo , Humanos
10.
Int J Mol Sci ; 22(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925284

RESUMO

High density lipoprotein (HDL) cholesterol has traditionally been considered the "good cholesterol", and most of the research regarding HDL cholesterol has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within atherosclerotic cardiovascular disease. Randomized trials aiming at increasing HDL cholesterol have, however, failed and left questions to what role HDL cholesterol plays in human health and disease. Recent observational studies involving non-cardiovascular diseases have shown that high levels of HDL cholesterol are not necessarily associated with beneficial outcomes as observed for age-related macular degeneration, type II diabetes, dementia, infection, and mortality. In this narrative review, we discuss these interesting associations between HDL cholesterol and non-cardiovascular diseases, covering observational studies, human genetics, and plausible mechanisms.


Assuntos
HDL-Colesterol/efeitos adversos , HDL-Colesterol/metabolismo , HDL-Colesterol/fisiologia , Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doença/etiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Degeneração Macular , Fatores de Risco
11.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33924958

RESUMO

Living species are continuously subjected to all extrinsic forms of reactive oxidants and others that are produced endogenously. There is extensive literature on the generation and effects of reactive oxygen species (ROS) in biological processes, both in terms of alteration and their role in cellular signaling and regulatory pathways. Cells produce ROS as a controlled physiological process, but increasing ROS becomes pathological and leads to oxidative stress and disease. The induction of oxidative stress is an imbalance between the production of radical species and the antioxidant defense systems, which can cause damage to cellular biomolecules, including lipids, proteins and DNA. Cellular and biochemical experiments have been complemented in various ways to explain the biological chemistry of ROS oxidants. However, it is often unclear how this translates into chemical reactions involving redox changes. This review addresses this question and includes a robust mechanistic explanation of the chemical reactions of ROS and oxidative stress.


Assuntos
Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Animais , DNA/metabolismo , Dano ao DNA , Doença/etiologia , Humanos , Peroxidação de Lipídeos , Mitocôndrias/metabolismo , Neutrófilos/metabolismo , Fosforilação Oxidativa , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas/metabolismo
12.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925019

RESUMO

Periodontitis is considered a promoter of many systemic diseases, but the signaling pathways of this interconnection remain elusive. Recently, it became evident that certain microbial challenges promote a heightened response of myeloid cell populations to subsequent infections either with the same or other pathogens. This phenomenon involves changes in the cell epigenetic and transcription, and is referred to as ''trained immunity''. It acts via modulation of hematopoietic stem and progenitor cells (HSPCs). A main modulation driver is the sustained, persistent low-level transmission of lipopolysaccharide from the periodontal pocket into the peripheral blood. Subsequently, the neutrophil phenotype changes and neutrophils become hyper-responsive and prone to boosted formation of neutrophil extracellular traps (NET). Cytotoxic neutrophil proteases and histones are responsible for ulcer formations on the pocket epithelium, which foster bacteremia and endoxemia. The latter promote systemic low-grade inflammation (SLGI), a precondition for many systemic diseases and some of them, e.g., atherosclerosis, diabetes etc., can be triggered by SLGI alone. Either reverting the polarized neutrophils back to the homeostatic state or attenuation of neutrophil hyper-responsiveness in periodontitis might be an approach to diminish or even to prevent systemic diseases.


Assuntos
Doença/etiologia , Endotoxemia/imunologia , Neutrófilos/fisiologia , Periodontite/complicações , Animais , Endotoxemia/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Periodontite/imunologia , Periodontite/metabolismo
13.
Int J Mol Sci ; 22(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809447

RESUMO

Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering (activation step). The key feature of the triggering step is the activation of inflammasomes that are intracellular protein complexes consisting of pattern recognition receptors and inflammatory molecules. Inflammasomes are activated in response to various ligands, leading to the caspase-1-mediated maturation and secretion of pro-inflammatory cytokines, IL-1ß and IL-18 and the gasdermin D-mediated pyroptosis, an inflammatory form of cell death. Previous studies have demonstrated that inflammasome activation is a key determinant of inflammatory responses and many human diseases; therefore, inflammasomes have been attracted much attention as critical drug targets to prevent and treat various human diseases.


Assuntos
Doença , Inflamassomos/metabolismo , Animais , Biomarcadores/metabolismo , Flavonoides/farmacologia , Humanos , Inflamação/patologia , Camundongos
14.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800752

RESUMO

The members of the B7 family, as immune checkpoint molecules, can substantially regulate immune responses. Since microRNAs (miRs) can regulate gene expression post-transcriptionally, we conducted a scoping review to summarize and discuss the regulatory cross-talk between miRs and new B7 family immune checkpoint molecules, i.e., B7-H3, B7-H4, B7-H5, butyrophilin like 2 (BTNL2), B7-H6, B7-H7, and immunoglobulin like domain containing receptor 2 (ILDR2). The current study was performed using a six-stage methodology structure and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Embase, Scopus, Cochrane, ProQuest, and Google Scholar were systematically searched to obtain the relevant records to 5 November 2020. Two authors independently reviewed the obtained records and extracted the desired data. After quantitative and qualitative analyses, we used bioinformatics approaches to extend our knowledge about the regulatory cross-talk between miRs and the abovementioned B7 family members. Twenty-seven articles were identified that fulfilled the inclusion criteria. Studies with different designs reported gene-miR regulatory axes in various cancer and non-cancer diseases. The regulatory cross-talk between the aforementioned B7 family molecules and miRs might provide valuable insights into the pathogenesis of various human diseases.


Assuntos
Antígenos B7/fisiologia , Proteínas de Checkpoint Imunológico/fisiologia , MicroRNAs/fisiologia , Antígenos B7/genética , Antígenos B7/imunologia , Coagulação Sanguínea , Quimiocinas/fisiologia , Ativação do Complemento , Biologia Computacional/métodos , Doença/genética , Redes Reguladoras de Genes , Humanos , Proteínas de Checkpoint Imunológico/genética , Proteínas de Checkpoint Imunológico/imunologia , MicroRNAs/genética , Transdução de Sinais
15.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803235

RESUMO

Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. The assessment of plasmin kinetics allows for the identification of fibrinolytic dysfunction and better understanding of the relationships between abnormal fibrin dissolution and disease pathogenesis. Additionally, direct measurement of the inhibition of PG by antifibrinolytic medications, such as tranexamic acid, can be a useful tool to assess the risks and effectiveness of antifibrinolytic therapy in hemorrhagic diseases. This review provides an overview of available PG assays to directly measure the kinetics of plasmin formation and inhibition in human and mouse plasmas and focuses on their applications in defining the role of plasmin in diseases, including angioedema, hemophilia, rare bleeding disorders, COVID-19, or diet-induced obesity. Moreover, this review introduces the PG assay as a promising clinical and research method to monitor antifibrinolytic medications and screen for genetic or acquired fibrinolytic disorders.


Assuntos
Análise Química do Sangue/métodos , Doença , Fibrinolisina/análise , Fibrinolisina/metabolismo , Animais , Antifibrinolíticos/sangue , Fibrina/análise , Fibrina/química , Fibrinolíticos/sangue , Humanos , Plasminogênio/análise , Plasminogênio/química , Plasminogênio/metabolismo
16.
Nat Commun ; 12(1): 2436, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893285

RESUMO

Genome-wide association studies (GWAS) are not fully comprehensive, as current strategies typically test only the additive model, exclude the X chromosome, and use only one reference panel for genotype imputation. We implement an extensive GWAS strategy, GUIDANCE, which improves genotype imputation by using multiple reference panels and includes the analysis of the X chromosome and non-additive models to test for association. We apply this methodology to 62,281 subjects across 22 age-related diseases and identify 94 genome-wide associated loci, including 26 previously unreported. Moreover, we observe that 27.7% of the 94 loci are missed if we use standard imputation strategies with a single reference panel, such as HRC, and only test the additive model. Among the new findings, we identify three novel low-frequency recessive variants with odds ratios larger than 4, which need at least a three-fold larger sample size to be detected under the additive model. This study highlights the benefits of applying innovative strategies to better uncover the genetic architecture of complex diseases.


Assuntos
Envelhecimento , Doença/genética , Predisposição Genética para Doença/genética , Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Fatores Etários , Frequência do Gene , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Genótipo , Haplótipos , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único
17.
Int J Mol Sci ; 22(8)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924313

RESUMO

The conserved nuclease-helicase DNA2 has been linked to mitochondrial myopathy, Seckel syndrome, and cancer. Across species, the protein is indispensable for cell proliferation. On the molecular level, DNA2 has been implicated in DNA double-strand break (DSB) repair, checkpoint activation, Okazaki fragment processing (OFP), and telomere homeostasis. More recently, a critical contribution of DNA2 to the replication stress response and recovery of stalled DNA replication forks (RFs) has emerged. Here, we review the available functional and phenotypic data and propose that the major cellular defects associated with DNA2 dysfunction, and the links that exist with human disease, can be rationalized through the fundamental importance of DNA2-dependent RF recovery to genome duplication. Being a crucial player at stalled RFs, DNA2 is a promising target for anti-cancer therapy aimed at eliminating cancer cells by replication-stress overload.


Assuntos
Instabilidade Cromossômica , DNA Helicases/metabolismo , Replicação do DNA , Animais , Sobrevivência Celular , DNA Helicases/química , DNA Mitocondrial/metabolismo , Doença/genética , Humanos
18.
An. Fac. Cienc. Méd. (Asunción) ; 54(1): 51-60, 20210000.
Artigo em Espanhol | LILACS | ID: biblio-1178618

RESUMO

Introducción: Actualmente el tabaquismo es una de las mayores amenazas para la salud pública a nivel mundial. La muerte atribuida al tabaco en Paraguay representa el 12,2% de todas las muertes y el costo de la enfermedad asociada al consumo de tabaco en el sistema de salud es elevado. Objetivos: El objetivo de este estudio es describir las características del consumo de tabaco en jóvenes en Paraguay. Materiales y métodos: Se realizó un estudio descriptivo transversal no probabilístico de muestreo estandarizado con representatividad nacional en estudiantes matriculados del 7° al 9° grado de la educación escolar básica, de 13 a 15 años de ambos sexos que incluyo a 6.518 estudiantes, correspondiente a 25 escuelas de la capital y 25 escuelas en el resto del país. Resultados: La prevalencia actual de consumo de productos de tabaco fue del 7%, fumadores actuales de 3,9% y fumadores de cigarrillos electrónicos de 3,7%. La prevalencia de fumadores de segunda mano fue más del 20% en todos los escenarios estudiados. Alto porcentaje de adolescentes con acceso fácil a la compra de cigarrillos sin verificación de la edad. Más del 50% con acceso a mensajes publicitarios sobre tabaco. Casi un 30% tenían conocimiento del efecto dañino del tabaco y más del 80% se manifiestan favorables a la prohibición de fumar en espacios cerrados y abiertos. Conclusión: Aunque la prevalencia de fumadores en adolescentes no es muy elevada, es un problema de salud pública creciente. Se requiere fortalecer las medidas de prevención y control.


Introduction: Currently, smoking is one of the greatest threats to public health worldwide. Death attributed to tobacco in Paraguay represents 12.2% of all deaths and the cost of the disease associated with tobacco consumption in the health system is high. Objectives: The objective of this study is to describe the characteristics of tobacco consumption in young people in Paraguay. Materials and methods: A non-probabilistic descriptive cross-sectional study of standardized sampling was carried out with national representativeness in students enrolled from 7th to 9th grade of basic school education, from 13 to 15 years old of both sexes that included 6,518 students, corresponding to 25 schools in the capital and 25 schools in the rest of the country. Results: The current prevalence of tobacco product use was 7%, current smokers 3.9%, and electronic cigarette smokers 3.7%. The prevalence of second-hand smokers was more than 20% in all the scenarios studied. High percentage of adolescents with easy access to the purchase of cigarettes without age verification. More than 50% with access to advertising messages about tobacco. Almost 30% were aware of the harmful effect of tobacco and more than 80% are in favor of the prohibition of smoking in closed and open spaces. Conclusion: Although the prevalence of smoking in adolescents is not very high, it is a growing public health problem. It is necessary to strengthen prevention and control measures.


Assuntos
Tabaco , Tabagismo , Uso de Tabaco , Estudantes , Doença , Prevalência , Custos e Análise de Custo , Controle
19.
BMC Bioinformatics ; 22(1): 165, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33781206

RESUMO

BACKGROUND: Exploring the relationship between disease and gene is of great significance for understanding the pathogenesis of disease and developing corresponding therapeutic measures. The prediction of disease-gene association by computational methods accelerates the process. RESULTS: Many existing methods cannot fully utilize the multi-dimensional biological entity relationship to predict disease-gene association due to multi-source heterogeneous data. This paper proposes FactorHNE, a factor graph-aggregated heterogeneous network embedding method for disease-gene association prediction, which captures a variety of semantic relationships between the heterogeneous nodes by factorization. It produces different semantic factor graphs and effectively aggregates a variety of semantic relationships, by using end-to-end multi-perspectives loss function to optimize model. Then it produces good nodes embedding to prediction disease-gene association. CONCLUSIONS: Experimental verification and analysis show FactorHNE has better performance and scalability than the existing models. It also has good interpretability and can be extended to large-scale biomedical network data analysis.


Assuntos
Doença , Genes , Semântica , Doença/genética , Predisposição Genética para Doença , Humanos
20.
Cell Mol Life Sci ; 78(7): 3317-3331, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33755743

RESUMO

Extracellular NAD represents a key signaling molecule in different physiological and pathological conditions. It exerts such function both directly, through the activation of specific purinergic receptors, or indirectly, serving as substrate of ectoenzymes, such as CD73, nucleotide pyrophosphatase/phosphodiesterase 1, CD38 and its paralog CD157, and ecto ADP ribosyltransferases. By hydrolyzing NAD, these enzymes dictate extracellular NAD availability, thus regulating its direct signaling role. In addition, they can generate from NAD smaller signaling molecules, like the immunomodulator adenosine, or they can use NAD to ADP-ribosylate various extracellular proteins and membrane receptors, with significant impact on the control of immunity, inflammatory response, tumorigenesis, and other diseases. Besides, they release from NAD several pyridine metabolites that can be taken up by the cell for the intracellular regeneration of NAD itself. The extracellular environment also hosts nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase, which inside the cell catalyze key reactions in NAD salvaging pathways. The extracellular forms of these enzymes behave as cytokines, with pro-inflammatory functions. This review summarizes the current knowledge on the extracellular NAD metabolome and describes the major biochemical properties of the enzymes involved in extracellular NAD metabolism, focusing on the contribution of their catalytic activities to the biological function. By uncovering the controversies and gaps in their characterization, further research directions are suggested, also to better exploit the great potential of these enzymes as therapeutic targets in various human diseases.


Assuntos
ADP Ribose Transferases/metabolismo , Doença , Metaboloma , NAD/metabolismo , Pentosiltransferases/metabolismo , Pirofosfatases/metabolismo , Animais , Humanos , Transdução de Sinais
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