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2.
Results Probl Cell Differ ; 67: 441-485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31435807

RESUMO

The Golgi apparatus is a central intracellular membrane-bound organelle with key functions in trafficking, processing, and sorting of newly synthesized membrane and secretory proteins and lipids. To best perform these functions, Golgi membranes form a unique stacked structure. The Golgi structure is dynamic but tightly regulated; it undergoes rapid disassembly and reassembly during the cell cycle of mammalian cells and is disrupted under certain stress and pathological conditions. In the past decade, significant amount of effort has been made to reveal the molecular mechanisms that regulate the Golgi membrane architecture and function. Here we review the major discoveries in the mechanisms of Golgi structure formation, regulation, and alteration in relation to its functions in physiological and pathological conditions to further our understanding of Golgi structure and function in health and diseases.


Assuntos
Doença , Complexo de Golgi/química , Complexo de Golgi/fisiologia , Saúde , Estresse Fisiológico , Animais , Transporte Biológico , Ciclo Celular , Humanos , Membranas Intracelulares/metabolismo
3.
Yi Chuan ; 41(7): 582-598, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31307968

RESUMO

Gene editing is a genetic manipulation technology which utilizes bacterial nucleases to accurately and efficiently modify DNA or RNA. Gene editing has broad applications in basic research, breeding, and drug screening, and it is gaining validity and applicability to the therapy of many diseases especially genetic-based disease. In this review, we summarize the development of gene editing technology, its different strategies and applications in the treatment of disease, and the research of gene editing therapy for genetic diseases (including base editor and epigenetic regulation) in the treatment of disorders and diseases of the blood system, liver, muscle and nervous system. Finally, we discuss the future development prospects of gene editing therapy.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/tendências , Terapia Genética , Doença , Epigênese Genética , Humanos
5.
Nature ; 571(7766): 489-499, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31341302

RESUMO

Epigenetic research has accelerated rapidly in the twenty-first century, generating justified excitement and hope, but also a degree of hype. Here we review how the field has evolved over the last few decades and reflect on some of the recent advances that are changing our understanding of biology. We discuss the interplay between epigenetics and DNA sequence variation as well as the implications of epigenetics for cellular memory and plasticity. We consider the effects of the environment and both intergenerational and transgenerational epigenetic inheritance on biology, disease and evolution. Finally, we present some new frontiers in epigenetics with implications for human health.


Assuntos
Doença/genética , Epigênese Genética/genética , Epigenômica/tendências , Interação Gene-Ambiente , Envelhecimento/genética , Animais , Cromatina/genética , Cromatina/metabolismo , Metilação de DNA/genética , Variação Genética/genética , Humanos , Neoplasias/genética
6.
Rev. Univ. Ind. Santander, Salud ; 51(2): 147-154, abr.-jun. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1003165

RESUMO

Resumen Introducción: La aplicación de una ley exponencial para los sistemas dinámicos caóticos cardiacos ha sido reducida a 18 horas para el análisis del Holter, cuantificando las dinámicas cardiacas normales y patológicas, así como la evolución entre estos estados. Metodología: Se analizaron 80 registros electrocardiográficos, 15 con dinámicas normales y 65 con diferentes patologías. Se construyó un atractor caótico para cada dinámica cardiaca a partir de la simulación de la secuencia de las frecuencias cardiacas durante 18 horas, posteriormente se halló la dimensión fractal de cada atractor y su ocupación espacial. Los parámetros diferenciadores de la ley caótica exponencial fueron aplicados diferenciando dinámicas cardiacas normales de aquellas patológicas, finalmente se calculó la sensibilidad, especificidad y coeficiente Kappa. Resultados: Las dinámicas normales presentaron espacios de ocupación por encima de 200 en la rejillla Kp, y para la rejilla Kg por encima de 67. Para los casos de enfermedad aguda los valores en las rejillas Kp y Kg estuvieron por debajo de 73 y 22 respectivamente. Los valores de sensibilidad y especificidad fueron de 100% y el coeficiente Kappa fue de 1. Conclusión: La aplicación de la ley exponencial durante 18 horas mostro que fue posible caracterizar matemáticamente las dinámicas cardiacas, permitiendo reducir el tiempo de evaluación.


Abstract Introduction: The application of an exponential law for chaotic dynamic cardiac systems has been reduced to 18 hours for Holter analysis, quantifying normal and pathological cardiac dynamics, as well as the evolution between these states. Methodology: 80 electrocardiographic records were analyzed, 15 with normal dynamics and 65 with different pathologies. A chaotic attractor was constructed for each cardiac dynamic based on the simulation of the cardiac frequency sequence for 18 hours, after the fractal dimension of each attractor and its spatial occupation were found. The differentiating parameters of the chaotic exponential law were applied differentiating normal cardiac dynamics from those pathological, finally the sensitivity, specificity and Kappa coefficient were calculated. Results: The normal dynamics presented occupancy spaces above 200 in the Kp grid, and for the Kg grid above 67. In the cases of acute disease, the values in the Kp and Kg grids were below 73 and 22 respectively. The values of sensitivity and specificity were 100% and the Kappa coefficient was 1. Conclusion: The application of the exponential law for 18 hours showed that it was possible to characterize mathematically the cardiac dynamics, allowing reducing the time of evaluation.


Assuntos
Humanos , Fractais , Doença , Simulação , Diagnóstico , Eletrocardiografia , Matemática
7.
BMC Bioinformatics ; 20(Suppl 12): 313, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31216978

RESUMO

BACKGROUND: Schizophrenia and autism are examples of polygenic diseases caused by a multitude of genetic variants, many of which are still poorly understood. Recently, both diseases have been associated with disrupted neuron motility and migration patterns, suggesting that aberrant cell motility is a phenotype for these neurological diseases. RESULTS: We formulate the POLYGENIC DISEASE PHENOTYPE Problem which seeks to identify candidate disease genes that may be associated with a phenotype such as cell motility. We present a machine learning approach to solve this problem for schizophrenia and autism genes within a brain-specific functional interaction network. Our method outperforms peer semi-supervised learning approaches, achieving better cross-validation accuracy across different sets of gold-standard positives. We identify top candidates for both schizophrenia and autism, and select six genes labeled as schizophrenia positives that are predicted to be associated with cell motility for follow-up experiments. CONCLUSIONS: Candidate genes predicted by our method suggest testable hypotheses about these genes’ role in cell motility regulation, offering a framework for generating predictions for experimental validation.


Assuntos
Movimento Celular/genética , Doença/genética , Redes Reguladoras de Genes , Herança Multifatorial/genética , Algoritmos , Transtorno Autístico/genética , Estudos de Associação Genética , Humanos , Aprendizado de Máquina , Fenótipo , Curva ROC , Reprodutibilidade dos Testes , Esquizofrenia/genética
8.
BMC Bioinformatics ; 20(1): 330, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196129

RESUMO

BACKGROUND: Ontology has attracted substantial attention from both academia and industry. Handling uncertainty reasoning is important in researching ontology. For example, when a patient is suffering from cirrhosis, the appearance of abdominal vein varices is four times more likely than the presence of bitter taste. Such medical knowledge is crucial for decision-making in various medical applications but is missing from existing medical ontologies. In this paper, we aim to discover medical knowledge probabilities from electronic medical record (EMR) texts to enrich ontologies. First, we build an ontology by identifying meaningful entity mentions from EMRs. Then, we propose a symptom-dependency-aware naïve Bayes classifier (SDNB) that is based on the assumption that there is a level of dependency among symptoms. To ensure the accuracy of the diagnostic classification, we incorporate the probability of a disease into the ontology via innovative approaches. RESULTS: We conduct a series of experiments to evaluate whether the proposed method can discover meaningful and accurate probabilities for medical knowledge. Based on over 30,000 deidentified medical records, we explore 336 abdominal diseases and 81 related symptoms. Among these 336 gastrointestinal diseases, the probabilities of 31 diseases are obtained via our method. These 31 probabilities of diseases and 189 conditional probabilities between diseases and the symptoms are added into the generated ontology. CONCLUSION: In this paper, we propose a medical knowledge probability discovery method that is based on the analysis and extraction of EMR text data for enriching a medical ontology with probability information. The experimental results demonstrate that the proposed method can effectively identify accurate medical knowledge probability information from EMR data. In addition, the proposed method can efficiently and accurately calculate the probability of a patient suffering from a specified disease, thereby demonstrating the advantage of combining an ontology and a symptom-dependency-aware naïve Bayes classifier.


Assuntos
Algoritmos , Teorema de Bayes , Técnicas e Procedimentos Diagnósticos , Registros Eletrônicos de Saúde , Bases de Conhecimento , Área Sob a Curva , Doença , Humanos , Probabilidade , Curva ROC
9.
Genome Biol ; 20(1): 105, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31155008

RESUMO

BACKGROUND: DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific. RESULTS: For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues. CONCLUSIONS: In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease.


Assuntos
Metilação de DNA , Epigênese Genética , Genoma Humano , Idoso , Encéfalo/metabolismo , Estudos de Casos e Controles , Criança , Doença/genética , Feminino , Gâmbia , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Estações do Ano , Glândula Tireoide/metabolismo
10.
Klin Lab Diagn ; 64(5): 299-307, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31185154

RESUMO

Modeling of tuberculosis infection is carried out in order to clarify various aspects of the tuberculosis pathogenesis, as well as the testing of new anti-tuberculosis drugs. The characteristic of in vitro models (n = 16) for Mycobacterium tuberculosis dormant state and in vivo models (n = 14) for the latent tuberculosis infection involving several animal species published to date are presented in this review. A brief description of the models and the results obtained by the authors are presented. The analysis of the published data reflects the list of methodological procedures that allow researchers to study the mechanism of the transition of M. tuberculosis cells to a dormant state and reverse to metabolically active state, as well as the process of conversion of active tuberculosis infection to a latent tuberculosis and reactivation.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Animais , Células Cultivadas , Doença , Modelos Animais de Doenças , Humanos
11.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(3): 314-319, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31218869

RESUMO

The proportion of mycobiome is less than 1% of human microbiome. However, fungal community plays a key role in human health and diseases. With high-throughput sequencing applications, the structure and composition of mycobiome in the mouth, lung, gut, vagina, and skin have been analyzed, and the role of microbiome in diseases has been investigated. Mycobiome also influences the composition of bacteriome and includes key species that maintain the structure and function of microbial communities. Fungi also influence host immune responses. In this review, we summarized the mycobiome com-position at various sites and different diseases and the interactions between fungi-bacteria and fungi-host.


Assuntos
Doença , Microbiota , Micobioma , Bactérias , Feminino , Fungos , Humanos , Boca
12.
Adv Clin Chem ; 90: 25-80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31122611

RESUMO

Acute-phase reactant serum amyloid A (A-SAA) plays an important role in acute and chronic inflammation and is used in clinical laboratories as an indicator of inflammation. Although both A-SAA and C-reactive protein (CRP) are acute-phase proteins, the detection of A-SAA is more conclusive than the detection of CRP in patients with viral infections, severe acute pancreatitis, and rejection reactions to kidney transplants. A-SAA has greater clinical diagnostic value in patients who are immunosuppressed, patients with cystic fibrosis who are treated with corticoids, and preterm infants with late-onset sepsis. Nevertheless, for the assessment of the inflammation status and identification of viral infection in other pathologies, such as bacterial infections, the combinatorial use of A-SAA and other acute-phase proteins (APPs), such as CRP and procalcitonin (PCT), can provide more information and sensitivity than the use of any of these proteins alone, and the information generated is important in guiding antibiotic therapy. In addition, A-SAA-associated diseases and the diagnostic value of A-SAA are discussed. However, the relationship between different A-SAA isotypes and their human diseases are mostly derived from research laboratories with limited clinical samples. Thus, further clinical evaluations are necessary to confirm the clinical significance of each A-SAA isotype. Furthermore, the currently available A-SAA assays are based on polyclonal antibodies, which lack isotype specificity and are associated with many inflammatory diseases. Therefore, these assays are usually used in combination with other biomarkers in the clinic.


Assuntos
Reação de Fase Aguda , Doença , Inflamação/sangue , Inflamação/diagnóstico , Proteína Amiloide A Sérica/análise , Amiloidose/sangue , Amiloidose/diagnóstico , Amiloidose/metabolismo , Animais , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/metabolismo , Humanos , Inflamação/metabolismo , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/metabolismo , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/metabolismo , Proteína Amiloide A Sérica/metabolismo
13.
Anal Chim Acta ; 1067: 11-30, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31047142

RESUMO

The employment of spectroscopically-resolved NMR techniques as analytical probes have previously been both prohibitively expensive and logistically challenging in view of the large sizes of high-field facilities. However, with recent advances in the miniaturisation of magnetic resonance technology, low-field, cryogen-free "benchtop" NMR instruments are seeing wider use. Indeed, these miniaturised spectrometers are utilised in areas ranging from food and agricultural analyses, through to human biofluid assays and disease monitoring. Therefore, it is both intrinsically timely and important to highlight current applications of this analytical strategy, and also provide an outlook for the future, where this approach may be applied to a wider range of analytical problems, both qualitatively and quantitatively.


Assuntos
Líquidos Corporais/química , Espectroscopia de Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/métodos , Animais , Doença , Medicina Legal , Humanos , Sistemas Automatizados de Assistência Junto ao Leito
14.
BMC Bioinformatics ; 20(1): 271, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138124

RESUMO

BACKGROUND: Networks have been widely used to model the structures of various biological systems. The ultimate aim of research on biological networks is to steer biological system structures to desired states by manipulating signals. Despite great advances in the linear control of single-layer networks, it has been observed that many complex biological systems have a multilayer networked structure and extremely complicated nonlinear processes. RESULT: In this study, we propose a general framework for controlling nonlinear dynamical systems with multilayer networked structures by formulating the problem as a minimum union optimization problem. In particular, we offer a novel approach for identifying the minimal driver nodes that can steer a multilayered nonlinear dynamical system toward any desired dynamical attractor. Three disease-related biology multilayer networks are used to demonstrate the effectiveness of our approaches. Moreover, in the set of minimum driver nodes identified by the algorithm we proposed, we confirmed that some nodes can act as drug targets in the biological experiments. Other nodes have not been reported as drug targets; however, they are also involved in important biological processes from existing literature. CONCLUSIONS: The proposed method could be a promising tool for determining higher drug target enrichment or more meaningful steering nodes for studying complex diseases.


Assuntos
Doença , Redes Reguladoras de Genes , Algoritmos , Comunicação Celular , Colite/complicações , Colite/genética , Neoplasias do Colo/complicações , Neoplasias do Colo/genética , Bases de Dados como Assunto , HIV-1/fisiologia , Humanos , Dinâmica não Linear
15.
Methods Mol Biol ; 1975: 427-454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31062321

RESUMO

The field of cell fate engineering is contingent on tools that can quantitatively assess the efficacy of cell fate engineering protocols and experiments. CellNet is such a cell fate assessment tool that utilizes network biology to both evaluate and suggest candidate transcriptional regulatory modifications to improve the similarity of an engineered population to its corresponding in vivo target population. CellNet takes in expression profiles in the form of RNA-sequencing data and generates several metrics of cell identity and protocol efficacy. In this chapter, we demonstrate how to (1) preprocess raw RNA-sequencing data to generate an expression matrix, (2) train CellNet using preprocessed expression matrices, and (3) apply CellNet to a query study and interpret its results. We demonstrate the utility of CellNet for analysis of iPSC disease modeling studies, which we evaluate through the lens of cell fate engineering.


Assuntos
Engenharia Celular/métodos , Linhagem da Célula , Biologia Computacional/métodos , Doença/genética , Regulação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/citologia , Software , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia
16.
Int J Mol Sci ; 20(9)2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31083592

RESUMO

The human body regenerates constantly in part under the control of signaling pathways that regulate cell growth [...].


Assuntos
Doença , Serina-Treonina Quinases TOR/metabolismo , Humanos , Neoplasias/metabolismo , Transdução de Sinais
17.
Adv Exp Med Biol ; 1132: 195-204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037636

RESUMO

In physiological condition, periostin is expressed in limited tissues such as periodontal ligament, periosteum, and heart valves. Periostin protein is mainly localized on extracellular collagen bundles and in matricellular space. On the other hand, in pathological condition, expression of periostin is induced in disordered tissues of human patients. In tumor development and progression, periostin is elevated mainly in its microenvironment and stromal tissue rich in extracellular matrix. Tumor stromal fibroblasts highly express periostin and organize the tumor-surrounding extracellular matrix architecture. In fibrosis in lung, liver, and kidney, proliferating activated fibroblasts express periostin and replace normal functional tissues with dense connective tissues. In inflammation and allergy, inflammatory cytokines such as IL-4 and IL-13 induce expression of periostin that plays important roles in pathogenesis of these diseases. The elevated levels of periostin in human patients could be detected not only in tissue biopsy samples but also in peripheral bloods using specific antibodies against periostin, because periostin secreted from the disordered tissues is transported into blood vessels and circulates in the cardiovascular system. In this chapter, I introduce the elevated expression of periostin in pathological conditions, and discuss how periostin could be utilized as a biomarker in disease diagnosis.


Assuntos
Biomarcadores/análise , Moléculas de Adesão Celular/análise , Doença , Matriz Extracelular , Fibroblastos , Fibrose , Humanos
18.
Adv Exp Med Biol ; 1132: 207-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037637

RESUMO

Since periostin is expressed and functioned in incredible diseases , clinical applications have been initiated to directly target periostin for inhibition or activation, or periostin expression is utilized to indicate the disease state or a marker for curing diseases, which will provide novel methods in clinical applications.


Assuntos
Moléculas de Adesão Celular/fisiologia , Terapia de Alvo Molecular , Biomarcadores , Doença , Humanos
19.
Molecules ; 24(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075966

RESUMO

Despite an increase in life expectancy that indicates positive human development, a new challenge is arising. Aging is positively associated with biological and cognitive degeneration, for instance cognitive decline, psychological impairment, and physical frailty. The elderly population is prone to oxidative stress due to the inefficiency of their endogenous antioxidant systems. As many studies showed an inverse relationship between carotenoids and age-related diseases (ARD) by reducing oxidative stress through interrupting the propagation of free radicals, carotenoid has been foreseen as a potential intervention for age-associated pathologies. Therefore, the role of carotenoids that counteract oxidative stress and promote healthy aging is worthy of further discussion. In this review, we discussed the underlying mechanisms of carotenoids involved in the prevention of ARD. Collectively, understanding the role of carotenoids in ARD would provide insights into a potential intervention that may affect the aging process, and subsequently promote healthy longevity.


Assuntos
Envelhecimento/fisiologia , Carotenoides/uso terapêutico , Doença , Disponibilidade Biológica , Carotenoides/efeitos adversos , Carotenoides/química , Carotenoides/metabolismo , Dieta , Humanos , Estresse Oxidativo
20.
BMC Bioinformatics ; 20(1): 260, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113357

RESUMO

BACKGROUND: Automatic extraction of chemical-disease relations (CDR) from unstructured text is of essential importance for disease treatment and drug development. Meanwhile, biomedical experts have built many highly-structured knowledge bases (KBs), which contain prior knowledge about chemicals and diseases. Prior knowledge provides strong support for CDR extraction. How to make full use of it is worth studying. RESULTS: This paper proposes a novel model called "Knowledge-guided Convolutional Networks (KCN)" to leverage prior knowledge for CDR extraction. The proposed model first learns knowledge representations including entity embeddings and relation embeddings from KBs. Then, entity embeddings are used to control the propagation of context features towards a chemical-disease pair with gated convolutions. After that, relation embeddings are employed to further capture the weighted context features by a shared attention pooling. Finally, the weighted context features containing additional knowledge information are used for CDR extraction. Experiments on the BioCreative V CDR dataset show that the proposed KCN achieves 71.28% F1-score, which outperforms most of the state-of-the-art systems. CONCLUSIONS: This paper proposes a novel CDR extraction model KCN to make full use of prior knowledge. Experimental results demonstrate that KCN could effectively integrate prior knowledge and contexts for the performance improvement.


Assuntos
Doença , Bases de Conhecimento , Mineração de Dados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos
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