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1.
Clin. transl. oncol. (Print) ; 25(11): 3296-3306, 11 nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-226852

RESUMO

Purpose The prognosis of advanced gastric cancer (GC) remains poor. It is urgent and necessary to find suitable prognostic markers. miR-619-5p is highly expressed in GC. However, the value of miR-619-5p and its target genes as prognostic biomarkers of GC is unclear. Methods RT-PCR was performed to verify the expression of miR-619-5p in GC cell lines and their exosomes. Western blotting and transmission electron microscope were used to identify exosomes. The target genes of miR-619-5p were predicted by RNA22 and TargetScan. The differentially expressed genes (DEGs) and prognosis-related genes (PRGs) were obtained using The Cancer Genome Atlas (TCGA) database. The DAVID database was used to analyse pathway enrichment and functional annotation of common target genes. The STRING database and Cytoscape software were used to screen key genes and visualize their functional modules. The survival analysis was conducted using TCGA and Kaplan–Meier Plotter (KMP) databases. Finally, a prognostic model was constructed on the foundation of the key genes to assess the reliability of the screening process. Results The expression of miR-619-5p in GC cells and their exosomes was proved to be significantly higher than that in normal cell lines. There are 129 common target genes involved in 3 pathways and 28 functional annotations. Finally, nine key target genes of GC (BRCA1, RAD51, KIF11, ERCC6L, BRIP1, TIMELESS, CDC25A, CLSPN and NCAPG2) were identified, and a prognostic model was successfully constructed with a good predictive ability. Conclusions The model of 9-gene signature could effectively predict the prognosis of GC, and have great potential to be novel prognostic factors and therapeutic targets for patients with GC (AU)


Assuntos
Humanos , Biologia Computacional , MicroRNAs/genética , Neoplasias Gástricas , Biomarcadores Tumorais , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Cromossômicas não Histona , Reprodutibilidade dos Testes , Prognóstico
2.
Arch. esp. urol. (Ed. impr.) ; 76(9): 680-689, 28 nov. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-228267

RESUMO

Objective: We conducted bioinformatics analysis of the gene chip data of empagliflozin for diabetic nephropathy (DN). The differentially expressed genes (DEGs) between DN and control mice and between DN and DN treated with empagliflozin (DNE) mice were screened to explore the related metabolic pathogenesis and predict the potential competing endogenous RNA (ceRNA)-related networks’ metabolic mechanism of the empagliflozin effect on DN. Methods: The intersection of DEGs in mice between the control and DN groups and between the DN and DNE groups was selected. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were performed, and the metabolic items involving the most genes in the coregulation were considered. A protein-interaction network was constructed with the STRING website. Cytoscape software and its plug-ins were utilised to analyse the hotspot differential genes. The noncoding RNAs in which the differential genes may play a role were obtained from the miRanda, miRDB, and TargetScan databases to establish network diagrams. Results: Analysis of the diabetes and control groups showed that 424 genes were upregulated and 354 were downregulated. In the analysis of DEGs between the DN and diabetic groups, the comparison between the diabetic and empagliflozin groups showed that 430 genes were upregulated and 84 were downregulated. The co-downregulated enrichment results were primarily reflected in various metabolic disorders, including glucose metabolism, lipid metabolism, amino acid metabolism, and others. The co-upregulated genes were associated with the inflammatory response, apoptosis, and cell senescence. This finding indicated that empagliflozin may inhibit the progression of diabetic nephropathy by inhibiting inflammation, apoptosis, and senescence. The key genes and related mechanisms of noncoding RNA were determined through Cytoscape analysis and the prediction of common DEGs in metabolic items (AU)


Assuntos
Animais , Camundongos , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Transdução de Sinais , Modelos Animais de Doenças , Biologia Computacional
3.
Int. microbiol ; 26(3): 501-511, Ene-Agos, 2023. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-223977

RESUMO

Climate change and environmental issues compel us to find alternatives to the production of molecules of interest from petrochemistry. This study aims at understanding the production of butyrate, hydrogen, and CO2 from the oxidation of lactate with acetate in Clostridium tyrobutyricum and thus proposes an alternative carbon source to glucose. This specie is known to produce more butyrate than the other butyrate-producing clostridia species due to a lack of solvent genesis phase. The recent discoveries on flavin-based electron bifurcation and confurcation mechanism as a mode of energy conservation led us to suggest a new metabolic scheme for the formation of butyrate from lactate-acetate co-metabolism. While searching for genes encoding for EtfAB complexes and neighboring genes in the genome of C. tyrobutyricum, we identified a cluster of genes involved in butyrate formation and another cluster involved in lactate oxidation homologous to Acetobacterium woodii. A phylogenetic approach encompassing other butyrate-producing and/or lactate-oxidizing species based on EtfAB complexes confirmed these results. A metabolic scheme on the production of butyrate, hydrogen, and CO2 from the lactate-acetate co-metabolism in C. tyrobutyricum was constructed and then confirmed with data of steady-state continuous culture. This in silico metabolic carbon flux analysis model showed the coherence of the scheme from the carbon recovery, the cofactor ratio, and the ATP yield. This study improves our understanding of the lactate oxidation metabolic pathways and the role of acetate and intracellular redox balance, and paves the way for the production of molecules of interest as butyrate and hydrogen with C. tyrobutyricum.(AU)


Assuntos
Humanos , Biologia Computacional/métodos , Clostridium tyrobutyricum , Oxidação , Ácido Láctico , Microbiologia , Técnicas Microbiológicas
4.
Allergol. immunopatol ; 51(3): 1-7, 01 mayo 2023. tab
Artigo em Inglês | IBECS | ID: ibc-219807

RESUMO

Background: Immune dysfunction is a common and serious complication of sepsis. This study finds key genes linked to immunity in sepsis. Methods: The “Limma package” was used to analyze GSE154918 datasets for differentially expressed genes. The differentially expressed genes were then enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and interleukin 2 receptor subunit Beta (IL2RB) protein coding gene was chosen for investigation. IL2RB expression in peripheral blood mononuclear cells (PBMC) was assessed by polymerase chain reaction. White blood cells of septic patients and healthy controls were collected from hospitals and linked with acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA), C-reactive protein (CRP), and procalcitonin (PCT) of septic patients using Pearson’s correlation analysis. PBMC cells were transfected with IL2RB, and the effect of transfection was observed on cellular interferon gamma (IFN-γ), interleukin (IL)-12, IL-4, IL-10, and IL-17A. Results: A total of 686 differential genes, comprising 446 upregulated and 240 down regulated genes, were identified. The enrichment of KEGG pathway revealed that the majority of differential genes were enriched in the T helper (Th1)/Th2 cell and Th17 cell differentiation pathways. In patients with sepsis, correlation analysis revealed a negative correlation between IL2RB and APACHE II score, SOFA score, CRP, and PCT. IFN-γ and IL-12 levels were elevated in PBMC of septic patients after IL2RB transfection, but IL-4, IL-10, and IL-17A levels were lowered. Conclusion: Sepsis-induced immunological dysfunction is improved by IL2RB, which also balances Th1/Th2 responses and prevents Th17 activation. © 2023 Codon Publications. Published by Codon Publications (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Receptores de Interleucina-2/imunologia , Células Th1/imunologia , Células Th2/imunologia , Sepse/imunologia , Biologia Computacional
5.
Allergol. immunopatol ; 51(1): 44-53, ene. 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-214021

RESUMO

Background/objective: Acute lung injury (ALI) is a critical clinical syndrome with high rates of incidence and mortality. However, its molecular mechanism remains unclear. The current work aimed to explore the molecular mechanisms of ALI by identifying different expression genes (DEGs) and candidate drugs using a combination of chip analysis and experimental validation. Methods: Three microarray datasets were downloaded from Gene Expression Omnibus (GEO) database to obtain DEGs. We conducted a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analyses of overlapping DEGs among three databases. The expression level of key gene was verified by Western blotting analysis in LPS-treated ALI cell models. Finally, we predicted the candidate drugs targeting the key gene that might be effective for ALI treatment, and the role of candidate drug in treating ALI was verified by investigation. Results: A total 29 overlapping DEGs were up-regulated in LPS-induced ALI groups. They were enriched in inflammation and inflammation-related pathways. Serpin family A member 3 (SERPINA3) was defined as a key gene because it was associated with inflammation pathway and up-regulated in microarray datasets in LPS-induced ALI. In LPS-induced human bronchial epithelial cells transformed with Ad12-SV40-2B (BEAS-2B) cells, SERPINA3 was enhanced. Pyridoxal phosphate as an upstream drug of SERPINA3 could improve cell viability and reduce expression inflammatory factors in LPS-treated BEAS-2B cells. Conclusion: Our study suggested that pyridoxal phosphate could be a candidate drug targeting SERPINA3 gene in LPS-induced ALI. It has protective and anti-inflammatory effects in BEAS-2B cells, and may become a potential novel treatment for ALI (AU)


Assuntos
Humanos , Biologia Computacional/métodos , Lesão Pulmonar Aguda/diagnóstico , Lipopolissacarídeos , Biomarcadores , Células Cultivadas , Expressão Gênica , Serpinas
6.
Allergol. immunopatol ; 51(1): 16-21, ene. 2023.
Artigo em Inglês | IBECS | ID: ibc-214035

RESUMO

Allergy is widely discussed by researchers due to its complex mechanism that leads to disorders and injuries, but the reason behind the allergic status remains unclear. Current treatments are insufficient to improve the patient’s quality of life significantly. New technologies in scientific and technological development are emerging. For instance, the union between allergy and peptidomics and bioinformatics tools may help fill the gaps in this field, diagnosis, and treatment. In this review, we look at peptidomics and address some findings, such as target proteins or biomarkers that help better understand mechanisms that lead to inflammation, organ damage, and, consequently, poor quality of life or even death (AU)


Assuntos
Humanos , Asma/genética , Hipersensibilidade/genética , Proteômica , Biologia Computacional , Predisposição Genética para Doença , Espectrometria de Massas
7.
Iberoam. j. med ; 5(1): 4-16, 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-226651

RESUMO

Introduction: Liver cancer is one of the most common malignant tumors in the world, and patients with liver cancer are often in the middle and late stages of cancer when they are diagnosed. Copper death is a newly discovered new cell death method. It is a copperdependent and regulated cell death method. At the same time, Long noncoding RNAs (LncRNAs) also play an important regulatory role in the pathological process of tumors such as liver cancer. Materials and methods: First, the expression levels of CuProtosis-related genes in liver cancer samples were extracted, and a CuProtosis- related LncRNA prognostic model was constructed. C-index curve and ROC curve were drawn by survival analysis, PFS analysis, and independent prognosis analysis. The model was also validated by clinical grouping and PCA principal component analysis. To ensure its accuracy, enrichment analysis, immune analysis and tumor mutational burden analysis further explored the potential function of this model, and finally discussed potential drugs targeting this model. Results: A prognostic model for predicting survival was constructed and its high predictive ability in liver cancer patients was validated. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that the differential genes were mainly enriched in 5 pathways. Meanwhile, six differentially expressed immune functions were found in the high-risk and low-risk groups. The survival rate of patients in the high mutation group was significantly lower than that of the patients with liver cancer in the low mutation group. Twelve drugs with significant differences in drug sensitivity between high- and low-risk groups were explored. Conclusions: ... (AU)


Introducción: El cáncer de hígado es uno de los tumores malignos más comunes en el mundo, y los pacientes con cáncer de hígado a menudo se encuentran en las etapas intermedia y tardía del cáncer cuando se les diagnostica. La muerte por cobre es un nuevo método de muerte celular recientemente descubierto. Es un método de muerte celular regulado y dependiente del cobre. Al mismo tiempo, los ARN no codificantes largos (LncRNA) también juegan un papel regulador importante en el proceso patológico de tumores como el cáncer de hígado. Materiales y métodos: En primer lugar, se extrajeron los niveles de expresión de genes relacionados con CuProtosis en muestras de cáncer de hígado y se construyó un modelo pronóstico de LncRNA relacionado con CuProtosis. La curva de índice C y la curva ROC se dibujaron mediante análisis de supervivencia, análisis de PFS y análisis de pronóstico independiente. El modelo también fue validado por agrupación clínica y análisis de componentes principales PCA. Para garantizar su precisión, el análisis de enriquecimiento, el análisis inmunitario y el análisis de la carga mutacional del tumor exploraron más a fondo la función potencial de este modelo y, finalmente, discutieron los posibles fármacos dirigidos a este modelo. Resultados: Se construyó un modelo pronóstico para predecir la supervivencia y se validó su alta capacidad predictiva en pacientes con cáncer de hígado. El enriquecimiento de Gene Ontology (GO) y el enriquecimiento de Kyoto Encyclopedia of Genes and Genomes (KEGG) mostraron que los genes diferenciales se enriquecieron principalmente en 5 vías. Mientras tanto, se encontraron seis funciones inmunes expresadas diferencialmente en los grupos de alto y bajo riesgo. La tasa de supervivencia de los pacientes en el grupo de alta mutación fue significativamente menor que la de los pacientes con cáncer de hígado en el grupo de baja mutación. ... (AU)


Assuntos
Humanos , Neoplasias Hepáticas , Previsões/métodos , RNA , Imunoterapia , Biologia Computacional , Carcinoma Hepatocelular
8.
Rev. toxicol ; 40(2): 81-86, 2023. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-229064

RESUMO

Resumen: Esta revisión resume los principales avances de la citogenética y proporciona una perspectiva sobre el futuro de la toxicología genética, desde el pasado, presente y futuro, tanto desde el punto de vista genético como epigenético. Los principios de la citogenética clásica han evolucionado con el tiempo, interactuando con enfoques de toxicología para dar lugar a la toxicología genética o mutagénesis ambiental. Actualmente, están surgiendo estudios toxicogenómicos basados en estudios de toxicología genética estándar, y uno de los principales objetivos de la toxicogenómica es detectar relaciones entre cambios en la expresión génica global y criterios de valoración toxicológicos, con el fin de comprender el papel de las interacciones gen-ambiente en la enfermedad. Para alcanzar este objetivo, la toxicogenómica combina la toxicología, la genética, tecnologías de perfiles moleculares de alto rendimiento como la transcriptómica, proteómica, metabolómica y la bioinformática. En este campo, muchas limitaciones restringen el papel de los nuevos hallazgos y enfoques. Por ejemplo, el costo de las nuevas tecnologías; sin embargo, su aplicación contribuirá a una mejor comprensión de las interacciones gen-ambiente y de esta manera, establecer políticas orientadas a prevenir riesgos para la salud, para que se viva una vida más saludable en un ambiente más favorable. (AU)


This review summarizes the main advances of cytogenetic and provides a perspective on the future of genetic toxicology, reviewing from past, present, and future, both genetics and epigenetic point of view. The principles of classical cytogenetics have evolved over time, interacting with toxicology approaches to give rise to genetic toxicology or environmental mutagenesis. Currently, toxicogenomic studies are emerging based on standard genetic toxicology studies, and one major goal of toxicogenomic is to detect relationships between changes in global gene expression and toxicological endpoints, in order to understand the role of gene-environment interactions in disease. To reach this goal, toxicogenomics combines toxicology, genetic, with genomics or other high throughput molecular profiling technologies such as transcriptomics, proteomics, metabolomics, and bioinformatics. In this field, many limitations are restricting the role of the novel findings and approaches. For example, the cost of new technologies; however, its application will contribute to a better understanding of gene-environment interactions and in this way, establish policies aimed at preventing health risks, so that a healthier life is lived in a friendlier environment. (AU)


Assuntos
Humanos , Toxicologia/história , Toxicologia/tendências , Ecotoxicologia/tendências , Citogenética/tendências , Mutagênese , Toxicogenética/tendências , Epigenômica/tendências , Biologia Computacional
9.
Arch. esp. urol. (Ed. impr.) ; 75(9): 779-790, 28 nov. 2022. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-212772

RESUMO

Background: Bladder cancer (BLCA) is an extremely common carcinoma of the urinary system that has a high incidence of relapse. Although intensive studies have investigated its pathology in the past decades, there are significant knowledge gaps regarding the characterization of the molecular processes underlying the progression of disease and consequently its prognosis. The purpose of current research was to identify significant genes that could serve as prognostic and progression biomarkers. Methods: Gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA) were conducted to recognize differential co-expression genes. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore gene function. Moreover, protein-protein interactions (PPI) network, overall survival (OS) and disease-free survival (DFS) were used to identify survival-related hub genes. Additionally, associations between these gene’s expression and clinical parameters were determined. Finally, the Human Protein Atlas (HPA) database and qRT-PCR were used to validate gene’s expression. Results: About 124 differential co-expression genes were identified. These genes were mainly enriched in muscle system process and muscle contraction (biological process, BP), contractile fiber, myofibril, sarcomere, focal adhesion and cell-substrate junction (cellular component, CC) and actin binding (molecular function, MF) in GO enrichment analysis, while enriched in vascular smooth muscle contraction, focal adhesion, cardiac muscle contraction, hypertrophic cardiomyopathy, dilated cardiomyopathy and regulation of actin cytoskeleton in KEGG analysis (AU)


Assuntos
Humanos , Neoplasias da Bexiga Urinária/genética , Biologia Computacional , Recidiva Local de Neoplasia , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Prognóstico
11.
Nutr. hosp ; 39(3): 569-579, may. - jun. 2022. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-209938

RESUMO

Objective: bioinformatic methods and molecular docking technology were used to predict the active components, targets, and related biological pathways of the Xiexin capsule in the intervention for dyslipidemia, exploring its mechanism. Methods: the active components and targets of the Xiexin capsule were screened by the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform )database. Genecards (The Human Gene Database), OMIM (Online Mendelian Inheritance in Man), PharmGkb (Pharmacogenomics Knowledge Base database), TTD (Therapeutic Target Database), and Drugbank platforms were used to search the disease targets of dyslipidemia. The Cytoscape 3.8.0 software was used to construct the 'component-target' network diagram, and the STRING (functional protein association networks) platform was used to analyze protein-protein interaction (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed by R language data packets to predict the mechanism of action. The AutoDockVina and PyMol software were used to dock the key active components in the Xiexin capsule and the core proteins in PPI. Results: a total of 66 effective components were screened, involving 114 targets; 87 key active compounds were screened from the 'drug-component-target' diagram. The PPI network mainly involved core proteins such as PTGS2 (prostaglandin-endoperoxide synthase 2), PTGS1 (prostaglandin-endoperoxide synthase 1), and HSP90AA1 (heat shock protein 90 alpha family class A member 1). GO and KEGG enrichment analysis results of common targets mainly involved hormone-mediated signaling pathway, steroid hormone response, lipid transport and metabolism, regulation of cholesterol storage, cyclooxygenase pathway, and other biological pathways, as well asMM PPAR (peroxisome proliferators-activated receptor) signaling pathway, IL-17 (interleukin 17) signaling pathway (AU)


Objetivo: se utilizaron métodos bioinformáticos y técnicas de acoplamiento molecular para predecir los componentes efectivos, los objetivos y las vías biológicas relacionadas de la cápsula Xiexin en la intervención de la dislipidemia y explorar su mecanismo. Métodos: los componentes activos y los objetivos de la cápsula Xiexin fueron seleccionados por la base de datos TCMSP. Se utilizaron las plataformas Genecards, OMIM, PharmGkb, TTD (Therapeutic Target Database) y Drugbank para buscar las dianas de la enfermedad en la dislipidemia. El diagrama reticular “componente-diana” fue construido por el software Cytoscape 3.7.0, y la interacción proteína-proteína (PPI) fue analizada por la plataforma STRING. Los análisis de enriquecimiento de Gene Ontology (GO) y Kyoto Encyclopedia of Genes and Genomics (KEGG) se realizaron mediante paquetes de datos en lenguaje R para predecir el mecanismo de acción. El software AutoDockVina y PyMol se utilizó para unir los componentes activos clave de la cápsula Xiexin y las proteínas clave de la PPI. Resultados: se seleccionaron 65 componentes activos y 114 dianas. Veintitrés compuestos activos clave fueron seleccionados a partir de la tabla “componentes farmacéuticos-dianas”. Las redes PPI incluyen principalmente proteínas básicas como PTGS2, PTGS1 y HSP90AA1. Los resultados del análisis de enriquecimiento de GO y KEGG en los objetivos comunes se refieren principalmente a la vía de señalización mediada por esteroides, la respuesta hormonal esteroidea, el transporte y metabolismo lipídicos, la regulación del almacenamiento de colesterol, la vía de la ciclooxigenasa y otras vías biológicas, así como la vía de señalización de PPAR, la vía de señalización de IL-17, la vía de señalización de PI3K-Akt (AU)


Assuntos
Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Dislipidemias/tratamento farmacológico , Cápsulas , Biologia Computacional/métodos , Simulação de Acoplamento Molecular , Receptores Ativados por Proliferador de Peroxissomo , Fosfatidilinositol 3-Quinase
12.
Clin. transl. oncol. (Print) ; 23(12): 2536-2547, dec. 2021. ilus
Artigo em Inglês | IBECS | ID: ibc-224111

RESUMO

Purpose Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). Methods We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. Results From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10−5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway (AU)


Assuntos
Humanos , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Estudo de Associação Genômica Ampla , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Biomarcadores Tumorais/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Seguimentos , Prognóstico , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Microambiente Tumoral
13.
Clin. transl. oncol. (Print) ; 23(9): 1866-1873, sept. 2021. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-222186

RESUMO

Purpose The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation. Methods Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma (n = 435) and normal samples (n = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 μM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation. Results Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3′-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p. Conclusions To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation (AU)


Assuntos
Humanos , Neoplasias Gástricas/patologia , Adenocarcinoma/patologia , Proliferação de Células/efeitos dos fármacos , MicroRNAs/metabolismo , Propofol/farmacologia , Fator de Transcrição STAT3/metabolismo , Regiões 3' não Traduzidas , Adenocarcinoma/metabolismo , Linhagem Celular Tumoral , Biologia Computacional , Ciclina D1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Mucosa Gástrica/metabolismo , Fator de Transcrição STAT3/genética , Neoplasias Gástricas/metabolismo
14.
Farm. hosp ; 44(6): 243-253, nov.-dic. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-197693

RESUMO

La rápida implantación clínica de las técnicas de secuenciación masiva en paralelo se debe a su capacidad para secuenciar un gran número de regiones genéticas con un coste menor a las técnicas convencionales. Sin embargo, su uso en el ámbito de la farmacogenética es, todavía, muy escaso. OBJETIVO: Diseño, desarrollo, implementación y validación de un panel de secuenciación masiva en paralelo de farmacogenética orientado a la práctica clínica. MÉTODO: Se desarrolló un panel de sondas de captura híbrida (Sure-Select(R)) para el análisis de las regiones genéticas de interés clínico recopiladas mediante búsqueda bibliográfica. Se empleó la plataforma de secuenciación Illumina HiSeq 1500(R). Se desarrolló un algoritmo de análisis bioinformático para la anotación de variantes puntuales, inferencia de haplotipos y determinación de variantes estructurales en los genes de interés. Los resultados obtenidos se validaron con materiales de referencia Coriell(R) de los repositorios de farmacogenética. RESULTADOS: El panel desarrollado permite el estudio de un total de 12.794 regiones comprendidas en 389 genes. Los resultados de validación mostraron una sensibilidad superior al 99% para variantes puntuales e inserciones y deleciones pequeñas. La imputación de haplotipos fue coherente con los resultados consenso de los materiales de referencia caracterizados. Además, la herramienta desarrollada pudo identificar correctamente diferentes tipos de variaciones de número de copias de CYP2D6, así como una gran variedad de alelos de HLA-B. CONCLUSIONES: Esta tecnología representa una alternativa adecuada para su empleo asistencial con ventajas frente a las técnicas convencionales en su rendimiento de producción y sus capacidades de estudio de genes complejos (CYP2D6, HLA-B)


The rapid clinical implementation of next generation sequencing techniques is due to its ability to sequence a large number of genetic regions at lower costs than conventional techniques. However, its use in the field of pharmacogenetics is still very limited. OBJECTIVE: Design, development, implementation and validation of a clinical pharmacogenetics next-generation sequencing panel. METHOD: We developed a panel of hybrid capture probes (SureSelect(R)) for the analysis of the genetic regions of clinical interest collected by literature search and using Illumina HiSeq 1500(R) sequencing platform. We developed a bioinformatic algorithm for variant annotation, haplotype inference and determination of structural variants in the genes of interest. The results obtained were validated with Coriell(R) reference material from the pharmacogenetic repositories. RESULTS: The developed panel allows the study of a total of 12,794 regions comprised in 389 genes. Validation results showed a sensitivity greater than 99% for single nucleotide variants and small INDELs. Haplotype imputation was consistent with the consensus results in the characterized reference materials. Furthermore, the developed tool was able to correctly identify different types of CYP2D6 copy number variations as well as a wide variety of HLA-B alleles. CONCLUSIONS: This technology represents an appropriate alternative for its clinical use with advantages over conventional techniques in its through-put and complex gene study capabilities (CYP2D6, HLA-B)


Assuntos
Humanos , Farmacogenética/métodos , Testes Farmacogenômicos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Medicina de Precisão/métodos , Algoritmos , Biologia Computacional , Citocromo P-450 CYP2D6/análise , Análise de Dados , Variantes Farmacogenômicos/genética
15.
Rev. esp. patol. torac ; 32(3): 229-242, oct. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-197930

RESUMO

OBJETIVO: Determinar si existen biomarcadores entre los transposones, tanto para diagnóstico como pronóstico de adenocarcinoma, carcinoma epidermoide y carcinoma microcítico de pulmón, así como valorar diferencias y similitudes entre estos tres tipos histológicos. MATERIAL Y MÉTODOS: Se ha secuenciado el RNA total del tejido tumoral y sano adyacente de muestras de adenocarcinoma y carcinoma epidermoide de dieciséis pacientes intervenidos en el Hospital Regional de Málaga. En el caso del carcinoma microcítico, se han utilizado pacientes externos cuyos datos proceden de los repositorios genómicos disponibles para la comunidad científica. Esas secuencias se han analizado con un flujo de trabajo bioinformático específico que conlleva varios pasos: 1º) Preprocesar las lecturas, 2º) Mapearlas sobre el genoma humano de referencia, 3º) Determinar la expresión de los transposones en cada una de las muestras, y 4º) Calcular su expresión diferencial entre el tejido sano y el tumoral de cada paciente. RESULTADOS: En un primer paso, hemos analizado los transposones con expresión diferencial en cada uno de los tipos histológicos estudiados por separado. El análisis del adenocarcinoma, carcinoma microcítico y carcinoma epidermoide de pulmón ha dado como resultado un total de 7, 72 y 12 transposones diferencialmente expresados (TDE), respectivamente. Hemos encontrado transposones comunes a los tres tipos histológicos y otros cuyo comportamiento es específico en cada uno de ellos. CONCLUSIONES: Los transposones se reprograman específicamente cuando una célula normal del pulmón se vuelve cancerosa. Esta reprogramación es una fuente de biomarcadores que podría ayudar al diagnóstico precoz del cáncer


OBJECTIVE: To determine whether biomarkers exist among transposons for both the diagnosis and prognosis of adenocarcinoma, squamous cell carcinoma and small cell carcinoma of the lung, as well as to evaluate differences and similarities between these three histological types. MATERIAL AND METHODS: The total RNA was sequenced for the tumor tissue and adjacent healthy tissue in adenocarcinoma and squamous cell carcinoma samples from sixteen patients being treated at the Hospital Regional de Málaga. In the case of small cell carcinoma, external patients were used whose data came from genomic repositories available to the scientific community. These sequences were analyzed with a specific bioinformatic workflow which includes several steps: 1) Pre-process readings, 2) Map them on the reference human genome, 3) Determine transposon expression in each of the samples, and 4) Calculate the differential expression between the healthy and tumor tissue in each patient. RESULTS: In the first step, we analyzed the transposons with differential expression in each of the histological types studied separately. The analysis of adenocarcinoma, small cell carcinoma and squamous cell carcinoma of the lung has resulted in a total of 7, 72 and 12 differentially expressed transposons, respectively. We found transposons common to all three histological types and others whose behavior is specific to each type. CONCLUSIONS: Transposons are specifically reprogrammed when a normal lung cell becomes cancerous. This reprogramming is a source of biomarkers that could help with the early diagnosis of cancer


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Retroelementos/genética , Elementos de DNA Transponíveis/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Carcinoma de Células Escamosas/diagnóstico , Adenocarcinoma/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Biomarcadores/análise , Prognóstico , Carcinoma de Células Escamosas/genética , Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Biologia Computacional , Diagnóstico Precoce
16.
Int. microbiol ; 22(4): 437-449, dic. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-185062

RESUMO

Azurin, a bacteriocin produced by a human gut bacterium Pseudomonas aeruginosa, can reveal selectively cytotoxic and induce apoptosis in cancer cells. After overcoming two phase I trials, a functional region of Azurin called p28 has been approved as a drug for the treatment of brain tumor glioma by FDA. The present study aims to improve a screening procedure and assess genetic diversity of Azurin genes in P. aeruginosa and Azurin-like genes in the gut microbiome of a specific population in Vietnam and global populations. Firstly, both cultivation-dependent and cultivation-independent techniques based on genomic and metagenomic DNAs extracted from fecal samples of the healthy specific population were performed and optimized to detect Azurin genes. Secondly, the Azurin gene sequences were analyzed and compared with global populations by using bioinformatics tools. Finally, the screening procedure improved from the first step was applied for screening Azurin-like genes, followed by the protein synthesis and NCI in vitro screening for anticancer activity. As a result, this study has successfully optimized the annealing temperatures to amplify DNAs for screening Azurin genes and applying to Azurin-like genes from human gut microbiota. The novelty of this study is the first of its kind to classify Azurin genes into five different genotypes at a global scale and confirm the potential anticancer activity of three Azurin-like synthetic proteins (Cnazu1, Dlazu11, and Ruazu12). The results contribute to the procedure development applied for screening anticancer proteins from human microbiome and a comprehensive understanding of their therapeutic response at a genetic level


No disponible


Assuntos
Azurina/genética , Técnicas In Vitro/métodos , Variação Genética/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Azurina/uso terapêutico , Bacteriocinas/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Metagenômica , Biologia Computacional/métodos , Antineoplásicos/farmacologia
17.
Int. microbiol ; 22(1): 7-17, mar. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-184809

RESUMO

The present study attempts to identify the novel inhibitors of shikimate dehydrogenase (SD), the enzyme that catalyzes the fourth reaction in the shikimate pathway, through virtual screening and toxicity studies. Crystal structure of SD was obtained from Protein Data Bank (PDB ID 4P4G, 1.7 Å) and subjected to energy minimization and structure optimization. A total of 13,803 compounds retrieved from two public databases and used for the virtual screening based on physicochemical properties (Lipinski rule of five) and molecular docking analyses. A total of 26 compounds with good AutoDock binding energies values ranging between −12.03 and −8.33 kcal/mol was selected and further filtered for absorption distribution metabolism excretion and toxicity analyses (ADMET). In this, eight compounds were selected, which satisfied all the ADME and toxicity analysis properties. Three compounds with better AutoDock binding energies values (ZINC12135132, −12.03 kcal/mol; ZINC08951370, −10.04 kcal/mol; and ZINC14733847, 9.82 kcal/mol) were considered for molecular dynamic (MD) simulation and molecular generalized born surface area (MM-GBSA) analyses. The results of the analyses revealed that the two ligands (ZINC12135132 and ZINC08951370) had better inhibitory activities within their complexes, after the 50-ns MD simulation, which suggested that the complexes formed stable conformation. It is noteworthy that compounds identified by docking, MD simulation, and MM-GBSA methods could be a drug for tuberculosis which required further experimental validation


No disponible


Assuntos
Oxirredutases/administração & dosagem , Tuberculose/tratamento farmacológico , Oxirredutases do Álcool/antagonistas & inibidores , Antituberculosos/isolamento & purificação , Biologia Computacional/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/isolamento & purificação , Tuberculose/microbiologia , Oxirredutases do Álcool/química , Antituberculosos/toxicidade , Inibidores Enzimáticos/toxicidade , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica
18.
Int. microbiol ; 22(1): 69-80, mar. 2019. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-184815

RESUMO

Shikimate dehydrogenase (HpSDH) (EC 1.1.1.25) is a key enzyme in the shikimate pathway of Helicobacter pylori (H. pylori), which catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate. Targeting HpSDH has been recognized as an attractive therapeutic strategy against H. pylori infection. Here, the catalytic active site in the crystal structure of HpSDH in complex with its substrate NADPH and product shikimate was examined in detail; the site can be divided into three spatially separated subpockets that separately correspond to the binding regions of shikimate, NADPH dihydronicotinamide moiety, and NADPH adenine moiety. Subsequently, a cascading protocol that integrated virtual screening and antibacterial test was performed against a biogenic compound library to identify biologically active, subpocket-specific inhibitors. Consequently, five, eight, and six promising compounds for, respectively, subpockets 1, 2, and 3 were selected from the top-100 docking-ranked hits, from which 11 compounds were determined to have high or moderate antibacterial potencies against two reference H. pylori strains, with MIC range between 8 and 93 μg/mL. It is found that the HpSDH active site prefers to accommodate amphipathic and polar inhibitors that consist of an aromatic core as well as a number of oxygen-rich polar/charged substituents such as hydroxyl, carbonyl, and carboxyl groups. Subpockets 1- and 2-specific inhibitors exhibit a generally higher activity than subpocket 3-specific inhibitors. Molecular dynamics simulations revealed an intense nonbonded network of hydrogen bonds, π-π stacking, and van der Waals contacts at the tightly packed complex interfaces of active-site subpockets with their cognate inhibitors, conferring strong stability and specificity to these complex systems. Binding energetic analysis demonstrated that the identified potent inhibitors can target their cognate subpockets with an effective selectivity over noncognate ones


No disponible


Assuntos
Oxirredutases do Álcool/antagonistas & inibidores , Antibacterianos/isolamento & purificação , Biologia Computacional , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/isolamento & purificação , Helicobacter pylori/enzimologia , Antibacterianos/química , Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Domínio Catalítico , Cristalografia por Raios X , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Conformação Proteica
19.
J. physiol. biochem ; 74(3): 491-501, ago. 2018. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-179002

RESUMO

Glycosylation of cell surface proteins regulates critical cellular functions, including invasion and metastasis in cancer cells. Emerging evidence has shown that microRNAs (miRNAs) are involved in regulating both the glycosylation modifications on cell surface and the progression of cancer. In this study, we investigated the role of miR-9 in alfa -2,6-linked sialylation and the metastasis of mouse hepatocellular carcinoma (HCC). According to array-based miRNA expression profiling data of HCC cell lines Hepa1-6, Hca-P, and Hca-F with different lymphatic metastatic capacities, reverse correlation was found between miR-9 expression levels and the metastatic potential in these HCC cells. Additionally, Beta-galactoside alfa -2,6-sialyltransferase 1 (St6gal1) expression level is associated negatively with miR-9 and positively with metastatic potential. Bioinformatics analysis indicated that miR-9 could target St6gal1, which was verified by luciferase reporter assays. miR-9 overexpression reduced expression of St6gal1, which subsequently suppressed HCC cells metastatic potential. Moreover, upregulation of miR-9 could inhibit integrin-Beta1/FAK-mediated cell motility and migration signaling in mouse HCC cells. Together, our results suggest that miR-9 could act as a tumor suppressor and regulate mouse HCC cells migration and invasion by inhibiting the alfa-2,6-linked sialylation. This finding may provide insight into the relationship between abnormal miRNA expression and aberrant cell surface glycosylation during tumor lymphatic metastasis


Assuntos
Humanos , Animais , Camundongos , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas Experimentais/genética , MicroRNAs/genética , Sialiltransferases/genética , Sequência de Bases , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular , Linhagem Celular Tumoral , Biologia Computacional , Quinase 1 de Adesão Focal , Glicosilação , Luciferases , Metástase Linfática
20.
Rev. osteoporos. metab. miner. (Internet) ; 10(2): 71-81, abr.-jun. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-178600

RESUMO

Objetivos: Identificación de potenciales biomarcadores implicados en procesos de calcificación vascular para avanzar en el diagnóstico y tratamiento de esta patología en sus estadíos subclínicos. Métodos: Se trata de un trabajo experimental en el que se incluyeron 5 pacientes con diabetes mellitus tipo 2 (DM2) con enfermedad arterial periférica e isquemia crítica. Se realizó una extracción proteica e identificación del proteoma mediante cromatografía líquida y espectrometría de masas (LC-MS/MS) de secciones de arteria femoral calcificada. Las proteínas identificadas fueron analizadas a través de gene ontology y comparadas con otras proteínas específicas de patologías vasculares relacionadas mediante la base de datos DisGeNET. Mediante el programa informático Cytoscape se analizó la red de funciones biológicas de las proteínas seleccionadas para su clasificación en base a la patología en la que están implicadas. Resultados: Se identificaron 530 proteínas en las muestras analizadas con funciones mayoritariamente de unión a calcio y catalítica. 37 de ellas fueron comunes en otras patologías vasculares relacionadas. La exploración de las redes biológicas de las 37 proteínas identificadas, dio lugar a la identificación de 2 potenciales marcadores específicos de calcificación vascular en procesos ateroscleróticos, como la proteína mitocondrial de choque térmico de 10 kDa, y la subunidad flavoproteica de la succinato deshidrogenasa. Conclusiones: Existe una importante expresión de proteínas implicadas en procesos de mineralización ósea en tejido vascular calcificado, sugiriendo la existencia de mecanismos moleculares comunes entre la regulación ósea y vascular. El uso de herramientas bioinformáticas sugiere la implicación de la proteína de choque térmico de 10 kDa mitocondrial y la subunidad flavoproteica de la succinato deshidrogenasa como posibles biomarcadores de calcificación vascular en pacientes con DM2, aunque son necesarios estudios adicionales que confirmen esta hipótesis


Objectives: Identify potential biomarkers involved in vascular calcification processes to improve DM2 diagnosis and treatment in its subclinical stages. Methods: This experimental study included 5 patients suffering diabetes mellitus type 2 (DM2) with peripheral arterial disease and critical ischemia. Protein extraction and identification of the proteome were carried out using liquid chromatography and mass spectrometry (LC-MS/MS) of calcified femoral artery sections. The identified proteins were analyzed through gene ontology and compared with other specific proteins of related vascular pathologies through the DisGeNET database. Cytoscape software analyzed the network of biological functions of the proteins selected for classification based on the disease in which they are involved. Results: 530 proteins were identified in the analyzed samples with functions mainly of calcium binding and catalytic. 37 of them were common in other related vascular pathologies. The exploration of the biological networks of the 37 proteins identified, led to the identification of 2 potential specific markers of vascular calcification in atherosclerotic processes, such as 10-kDa thermal shock mitochondrial protein, and the flavoprotein subunit of succinate dehydrogenase. Conclusions: There is significant expression of proteins involved in processes of bone mineralization in calcified vascular tissue, suggesting the existence of common molecular mechanisms between bone regulation and vascular. The use of bioinformatics tools suggests the involvement of the mitochondrial 10 kDa heat shock protein and the subunit of the succinate dehydrogenase as potential biomarkers of vascular calcification in patients with DM2, although additional studies are needed to confirm this hypothesis


Assuntos
Humanos , Biomarcadores/sangue , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/diagnóstico , Biologia Computacional , Aterosclerose/sangue , Aterosclerose/diagnóstico , Espectrometria de Massas
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