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1.
Rev. colomb. cardiol ; 26(1): 24-30, ene.-feb. 2019. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1058376

ABSTRACT

Resumen Las enfermedades cardiovasculares son la principal causa de muerte en el mundo. Fármacos hipolipemiantes como las estatinas son la primera alternativa en la prevención primaria de eventos cardiovasculares, ictus cerebrales y procedimientos de revascularización. Estos fármacos son inhibidores de la enzima HMG-CoA reductasa, la cual regula la velocidad de la síntesis del colesterol y además aumenta la captación hepática del mismo por la vía del receptor de las LDL. El polipéptido transportador de aniones orgánicos 1B1 (OATP1B1) codificado por el gen SLCO1B1 es uno de los transportadores de captación y eflujo hepático de las estatinas. Por medio de estudios de asociación de genomas completos se han reportado diferentes SNPs dentro del gen SLCO1B1 con capacidad de reducir la captación de estatinas mediada por OATP1B1, por lo que las variaciones en la secuencia de este gen influyen en la farmacocinética y farmacodinámica de estos medicamentos, llegando a causar una condición conocida como miopatía inducida por estatinas. En la actualidad, genes que afectan las terapias cardiovasculares, así como los avances actuales en el campo de las pruebas diagnósticas basadas en la secuenciación de los mismos, ofrecen la posibilidad de revolucionar el diagnóstico y el tratamiento con el fin de validar el riesgo de predicción, pronóstico, prevención y manejo de pacientes con riesgo de enfermedades cardiovasculares, lo cual conducirá al desarrollo de nuevas formas de tratamientos médicos.


Abstract Cardiovascular diseases are the main cause of death in the world. Lipid-lowering drugs like statins are the first alternative in the primary prevention of cardiovascular events, strokes, and revascularisation procedures. These drugs are HMG-CoA reductase inhibitors, which regulate the rate of cholesterol synthesis, as well as increase its liver uptake via the LDL receptor pathway. The organic anion transporter polypeptide 1B1 (OATP1B1) coded by the solute carrier organic anion transporter 1B1 (SLCO1B1) gene is one of the hepatic influx and efflux transporters of statins. In genome-wide association studies (GWAS) different single nucleotide polymorphisms (SNPs) have been reported within the SLCO1B1 gene that are able to reduce the statin uptake mediated by OATP1B1. This suggests that the variations in the sequencing of this gene have an influence on the pharmacokinetics and pharmacodynamics of these drugs, leading to a condition known as statin-induced myopathy. Genes that affect cardiovascular treatments, as well as the current advances in diagnostic tests based on their sequencing, now offer the possibility of revolutionising their diagnosis and treatment. They could be used with the aim of validating risk prediction, prognosis, prevention, and management of patients with a risk of cardiovascular diseases, and will lead to the development of new forms of medical treatments.


Subject(s)
Humans , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Genes, vif , Liver-Specific Organic Anion Transporter 1 , Pharmacogenomic Variants
2.
Article in English | WPRIM | ID: wpr-764365

ABSTRACT

BACKGROUND AND PURPOSE: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that plays an essential role in the maintenance of the nervous system. We have evaluated the peripheral blood protein levels of BDNF and the valine-to-methionine substitution at codon 66 (Val66Met) single-nucleotide polymorphism (SNP) as potential biomarkers for the early recognition of chemotherapy-induced peripheral neuropathy (CIPN) in non-Hodgkin lymphoma and multiple myeloma patients. METHODS: CIPN was assessed in 45 patients at the diagnosis and during vincristine or bortezomib-based therapy using objective [reduced version of the Total Neuropathy Score (TNSr)] and subjective (FACT-GOG-NTx) tools. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) questionnaire. BDNF protein levels and the Val66Met SNP were determined using ELISA and Sanger sequencing. RESULTS: The pretreatment BDNF protein level was inversely correlated with the maximum TNSr, FACT-GOG-NTx, and PHQ-9 scores in both genotypes. BDNF patients with the Val/Val genotype demonstrated significantly higher maximum FACT-GOG-NTx and PHQ-9 scores than those with the Val/Met and Met/Met genotypes (Met-BNDF carriers). Correlations between PHQ-9 and TNSr score were found only in Met-BDNF carriers, suggesting that peripheral neuropathy and depression coincide in Met-BDNF carriers. CONCLUSIONS: Determining the BDNF protein levels before initiating chemotherapy might be a useful tool for CIPN risk assessment and preemptive dose modification. The present data should be validated in larger studies that include other neurotoxic agents.


Subject(s)
Biomarkers , Brain-Derived Neurotrophic Factor , Codon , Depression , Diagnosis , Drug Therapy , Enzyme-Linked Immunosorbent Assay , Genes, vif , Genotype , Humans , Lymphoma , Lymphoma, Non-Hodgkin , Multiple Myeloma , Nervous System , Neurons , Peripheral Nervous System Diseases , Risk Assessment , Vincristine
3.
Article in English | WPRIM | ID: wpr-761725

ABSTRACT

This study was done to characterize distribution of Rickettsia spp. in ticks in the northwestern and southwestern provinces in the Republic of Korea. A total of 2,814 ticks were collected between May and September 2009. After pooling, 284 tick DNA samples were screened for a gene of Rickettsia-specific 17-kDa protein using nested PCR (nPCR), and produced 88 nPCR positive samples. Of these positives, 75% contained 190-kDa outer membrane protein gene (ompA), 50% 120-kDa outer membrane protein gene (ompB), and 64.7% gene D (sca4). The nPCR products of ompA, ompB, and sca4 genes revealed close relatedness to Rickettsia japonica, R. heilongjiangensis, and R. monacensis. Most Rickettsia species were detected in Haemaphysalis longicornis. This tick was found a dominant vector of rickettsiae in the study regions in the Republic of Korea.


Subject(s)
DNA , Genes, vif , Membrane Proteins , Polymerase Chain Reaction , Republic of Korea , Rickettsia , Ticks
4.
Article in English | WPRIM | ID: wpr-742449

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. METHODS: Mouse AE II cell line MLE-12 were exposed to 1–10 µg/mL BLM and 0.01–100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. RESULTS: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor β1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. CONCLUSION: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.


Subject(s)
Animals , Apoptosis , Bisbenzimidazole , Bleomycin , Cell Cycle Checkpoints , Cell Cycle , Cell Line , Cell Survival , Cytokines , Enzyme-Linked Immunosorbent Assay , Epithelial Cells , Gene Expression , Genes, vif , Humans , Idiopathic Pulmonary Fibrosis , Interleukin-6 , Lung , Mice , Propidium , RNA, Messenger , Transforming Growth Factors , Tumor Necrosis Factor-alpha
5.
Article in English | WPRIM | ID: wpr-742304

ABSTRACT

This study was undertaken to determine the complete mitochondrial DNA sequence and structure of the mitochondrial genome of Spirometra ranarum, and to compare it with those of S. erinaceieuropaei and S. decipiens. The aim of this study was to provide information of the species level taxonomy of Spirometra spp. using the mitochondrial genomes of 3 Spirometra tapeworms. The S. ranarum isolate originated from Myanmar. The mitochondrial genome sequence of S. ranarum was compared with that of S. erinaceieuropaei (GenBank no. KJ599680) and S. decipiens (Gen-Bank no. KJ599679). The complete mtDNA sequence of S. ranarum comprised 13,644 bp. The S. ranarum mt genome contained 36 genes comprising 12 protein-coding genes, 22 tRNAs and 2 rRNAs. The mt genome lacked the atp8 gene, as found for other cestodes. All genes in the S. ranarum mitochondrial genome are transcribed in the same direction and arranged in the same relative position with respect to gene loci as found for S. erinaceieuropaei and S. decipiens mt genomes. The overall nucleotide sequence divergence of 12 protein-coding genes between S. ranarum and S. decipiens differed by 1.5%, and 100% sequence similarity was found in the cox2 and nad6 genes, while the DNA sequence divergence of the cox1, nad1, and nad4 genes of S. ranarum and S. decipiens was 2.2%, 2.1%, and 2.6%, respectively.


Subject(s)
Base Sequence , Cestoda , Classification , DNA, Mitochondrial , Genes, vif , Genome , Genome, Mitochondrial , Myanmar , RNA, Transfer , Spirometra
6.
Article in English | WPRIM | ID: wpr-739668

ABSTRACT

BACKGROUND: Venous thromboembolism is a common complication in patients with glioma. The clotting factor von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. In the current analysis, we examined The Cancer Genome Atlas (TCGA) data to assess the VWF gene in patients with lower grade gliomas. METHODS: For newly diagnosed gliomas, we evaluated the association between VWF and overall survival in the Genomic Data Commons TCGA Lower Grade Glioma (LGG) dataset in TCGA. Simple statistics were calculated to identify patterns of mutual exclusivity or co-occurrence of VWF mutations. For each pair of query genes an odds ratio was calculated that indicates the likelihood that the mutations in the two genes are mutually exclusive or co-occurrent across the selected cases. To determine whether the identified relationship was significant for a gene pair, Fisher's exact test was performed. RESULTS: Lower grade gliomas with less VWF gene expression had significantly better survival than those with more VWF gene expression (hazard ratio 0.64, 95% confidence interval 0.44 to 0.92, p=0.015 log rank test). When we analyzed the data with Cox regression, VWF expression had a significant effect on survival (p=0.02) that was unrelated to the effect of IDH1 expression (p=0.062), TP53 expression (p=0.135), independent of ATRX expression (p=0.021) and histology (astrocytoma versus oligoastrocytoma and oligodendroglioma, p=0.002). VWF mutations significantly co-occur with mutations in TP53 and ATRX (p<0.001). CONCLUSION: The deleterious prognostic effect of VWF expression and its co-occurrent mutations with TP53 and ATRX in lower grade gliomas are not surprising, given VWF's role in other cancers. Therefore, VWF gene expression may be a clinically important risk marker in lower grade glioma.


Subject(s)
Adhesives , Blood Platelets , Dataset , Gene Expression , Genes, vif , Genome , Glioblastoma , Glioma , Humans , Odds Ratio , Oligodendroglioma , Venous Thromboembolism , von Willebrand Factor
7.
Article in English | WPRIM | ID: wpr-787284

ABSTRACT

Serine protease inhibitor Kazal-type 1 (SPINK1) is a gene expressed from pancreatic acinar cell which its mutation is known to be associated with chronic pancreatitis (CP) and pancreatic cancer. We report a case of a 47-years-old female with nausea and weight loss with yellow discoloration of skin. Initial imaging and endoscopic study led us to an impression of chronic pancreatitis with pancreatic cancer with common bile-duct dilation. Biopsy result was confirmed with pancreatic adenocarcinoma and additional imaging revealed lymph node and bone metastasis. Our genetic analysis revealed 194+2T>C mutation of SPINK1. Biliary obstruction was successfully decompressed by stent insertion and underwent chemotherapy and radiotherapy. Although there is accumulating evidence of association between SPINK1 mutation and CP, the relationship between SPINK1 mutation and pancreatic cancer in CP patient is an emerging concept. Genetic analysis should be considered in patients with young age especially when diagnosed with both CP and pancreatic cancer.


Subject(s)
Acinar Cells , Adenocarcinoma , Biopsy , Drug Therapy , Female , Genes, vif , Humans , Jaundice, Obstructive , Lymph Nodes , Nausea , Neoplasm Metastasis , Pancreatic Neoplasms , Pancreatitis, Chronic , Radiotherapy , Serine Proteases , Skin , Stents , Weight Loss
8.
Laboratory Animal Research ; : 165-171, 2019.
Article in English | WPRIM | ID: wpr-786407

ABSTRACT

Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.


Subject(s)
Animals , Computational Biology , Genes, vif , Genetic Association Studies , Humans , Mice , Phenotype , Systems Biology
9.
Article in Korean | WPRIM | ID: wpr-785902

ABSTRACT

PURPOSE: Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.MATERIALS AND METHODS: We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.RESULTS: At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.CONCLUSION: This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.


Subject(s)
Chemoradiotherapy , Colorectal Neoplasms , Dysbiosis , Fusobacterium , Gastrointestinal Microbiome , Genes, vif , Genome , Humans , Microbiota , Neoadjuvant Therapy , Prevotella , Radiotherapy , Rectal Neoplasms , Sequence Analysis, RNA , Transcriptome
10.
Article in English | WPRIM | ID: wpr-758794

ABSTRACT

Similar to other studies of bacterial pathogens, current studies of the pathogenesis of Riemerella anatipestifer (RA) are focused mainly on in vitro culture conditions. To elucidate further the pathogenesis of RA in vivo, bacterial RNA was extracted from overnight tryptic soy broth cultures (in vitro) and from the blood of infected ducks (in vivo) for comparative RNA sequencing analysis. In total, 682 upregulated genes were identified in vivo. Among the upregulated genes, a signal transduction response regulator (ArsR) and a signal transduction histidine kinase (SthK) were predicted to be located on the same operon. A mutant was constructed by deletion of both of these genes. Duck infection tests showed that genes ArsR and SthK were related to the virulence of the pathogen in vivo. Differentially expressed genes identified by comparison of in vitro and in vivo conditions provided an insight into the physiological process of RA infection and provided an opportunity to identify additional virulence factors.


Subject(s)
Ducks , Genes, vif , Histidine , In Vitro Techniques , Operon , Phosphotransferases , Physiological Phenomena , Riemerella , RNA, Bacterial , Sequence Analysis, RNA , Signal Transduction , Virulence Factors , Virulence
11.
Article in English | WPRIM | ID: wpr-742283

ABSTRACT

Acanthamoeba spp. are free-living protozoa that are opportunistic pathogens for humans. Cysteine proteases of Acanthamoeba have been partially characterized, but their biochemical and functional properties are not clearly understood yet. In this study, we isolated a gene encoding cysteine protease of A. castellanii (AcCP) and its biochemical and functional properties were analyzed. Sequence analysis of AcCP suggests that this enzyme is a typical cathepsin L family cysteine protease, which shares similar structural characteristics with other cathepsin L-like enzymes. The recombinant AcCP showed enzymatic activity in acidic conditions with an optimum at pH 4.0. The recombinant enzyme effectively hydrolyzed human proteins including hemoglobin, albumin, immunoglobuins A and G, and fibronectin at acidic pH. AcCP mainly localized in lysosomal compartment and its expression was observed in both trophozoites and cysts. AcCP was also identified in cultured medium of A. castellanii. Considering to lysosomal localization, secretion or release by trophozoites and continuous expression in trophozoites and cysts, the enzyme could be a multifunctional enzyme that plays important biological functions for nutrition, development and pathogenicity of A. castellanii. These results also imply that AcCP can be a promising target for development of chemotherapeutic drug for Acanthamoeba infections.


Subject(s)
Acanthamoeba castellanii , Acanthamoeba , Cathepsin L , Cathepsins , Cysteine Proteases , Cysteine , Fibronectins , Genes, vif , Humans , Hydrogen-Ion Concentration , Lysosomes , Sequence Analysis , Trophozoites , Virulence
12.
Article in English | WPRIM | ID: wpr-742250

ABSTRACT

In the present study, we identified a Spirometra species of Myanmar origin (plerocercoid) by molecular analysis using mitochondrial cox1 and nad1 genes, as well as by morphological observations of an adult tapeworm. Spargana specimens were collected from a paddy-field in Taik Kyi Township Tarkwa Village, Yangon, Myanmar in December 2017. A total of 5 spargana were obtained from 20 frogs Hoplobatrachus rugulosus; syn: Rana rugulosa (Wiegmann, 1834) or R. tigrina (Steindachner, 1867). The plerocercoids were used for experimental infection of a dog. After 4 weeks of infection, an adult tapeworm was recovered from the intestine of the dog. Morphologically, the distinct features of Spirometra sp. (Myanmar origin) relative to S. erinaceieuropaei and S. decipiens include a uterine morphology comprising posterior uterine coils that larger than the terminal uterine ball and coiling of the uteri diagonally (swirling) rather than spirally. The cox1 sequences (1,566 bp) of the Myanmar-origin Spirometra species showed 97.9% similarity to a reference sequence of S. decipiens (GenBank no. KJ599679) and 90.5% similarity to a reference sequence of S. erinaceieuropaei (GenBank no. KJ599680). Phylogenetic tree topologies were identical and presented high confidence level of values for the 3 major branches of the 3 Spirometra species in cox1 and nad1 genes. These results indicated that Myanmar-origin Spirometra species coincided with those of S. ranarum and may be considered as a valid species.


Subject(s)
Adult , Animals , Cestoda , Dogs , Genes, vif , Humans , Intestines , Myanmar , Ranidae , Spirometra , Trees , Uterus
13.
Rev. Investig. Salud. Univ. Boyacá ; 5(2): 205-218, 20180000. tab, graf. ilus
Article in Spanish | LILACS, COLNAL | ID: biblio-1005950

ABSTRACT

Introducción. La mastitis bovina es la inflamación de glándulas mamarias y tejidos secretores. El género Staphylococcus es el agente causal más importante, por su capacidad de producir diferentes factores de virulencia. Las enterotoxinas estafilocócicas son un grupo importante de toxinas que permiten al microorganismo invadir células y tejido huésped, son diseminadas por medio de productos alimenticios y son responsables de graves intoxicaciones alimentarias en el mundo. Objetivo. Determinar la presencia de genes codificadores para las enterotoxinas estafilocócicas (Staphylococcal Enterotoxins, SE) SEA, SEB, SEC, SED y SEE, en cepas de Staphylococcus spp. asociadas con mastitis bovina. Materiales y métodos. Se trata de un estudio cuantitativo, descriptivo y transversal. Se identificaron especies por medio de la amplificación de la región r16S. Los genes SEA, SEE, SEC, SED y SEE se detectaron mediante la amplificación por PCR convencional, usando iniciadores específicos para cada gen, y se evidenciaron los amplicones con electroforesis. Resultados. Hubo predominio del grupo Staphylococcus coagulasa positivo (65,2 %) sobre el grupo coagulasa negativo (37,5 %). Staphylococcus aureus fue la cepa más frecuente (88,5 %). El gen SEA (1,7 %) se detectó en S. sciuri, el gen SEB (3,6 %), en S. pasteuri y S. warneri, y el gen SEC (3,6 %), en S. sciuri y S. saprophyticus SEC. No se detectaron los genes SED y SEE en ninguna de las cepas evaluadas Conclusiones. Los resultados apoyan que la mastitis bovina también es causada por Staphylococcus coagulasa negativo, lo cual indica la posibilidad de que este grupo adquiera atributos genéticos, como enterotoxinas y factores de virulencia, por transferencia horizontal.


Introduction: Bovine mastitis is an inflammation of mammary glands and secretory tissues. Staphylococcus gender is the main causal agent, due to its capacity to produce different virulence factors. Staphylococcal enterotoxins are a main group of toxins which permit the microorganism to spread in cells and guest tissue, which are disseminated through food products, being responsible of serious food poisoning cases around the world. Objective: To determine the presence of coding genes for staphylococcal enterotoxins (SE); SEA, SEB, SEC, SED and SEE, in Staphylococcus spp. strains related to bovine mastitis. Materials and methods: Quantitative study, descriptive and cross-sectional. It was made an identification of species through. They were identified 57 Staphylococcus spp. strains at specie level by amplification of r16S region. The detection of SEA, SEE, SEC, SED, y SEE genes was made through conventional PCR, using specific primers for each gene, they were evinced amplicons through electrophoresis. Results: It was evinced predominance of coagulase-positive Staphylococcus group (65.2%), being Staphylococcus aureus the strain with the highest presence (88.5%), whereas coagulase-negative Staphylococcus group was 37.5%. SEA gene was detected in S. sciuri (1.7%); SEB in S. pasteuri and S. warneri (3.6%); SEC was identified in S. sciuri and S. saprophyticus (3.6%); they were not detected SED y SEE genes in any of the researched strains. Conclusions: The results support that the development of bovine mastitis is also caused by coagulase-negative Staphylococcus, indicating the possibility that this group acquires genetic attributes as enterotoxins and virulence factors by horizontal gene transfer.


Introdução. A mastite bovina é a inflamação das glândulas mamárias e dos tecidos secretórios. O gênero Staphylococcus é o agente causador mais importante, devido à sua capacidade de produzir diferentes fatores de virulência. As enterotoxinas estafilocócicas são um importante grupo de toxinas que permitem que o microorganismo invada as células e tecidos do hospede, são disseminadas através de produtos alimentícios e são responsáveis por intoxicações alimentares graves no mundo. Objetivo. Determinar a presença de genes que codificam enterotoxinas estafilocócicas (Staphylococcal Enterotoxins, SE) SEA, SEB, SEC, SED e SEE, em cepas de Staphylococcus spp. associada à mastite bovina. Materiais e métodos. Estudo quantitativo, descritivo e transversal. As espécies foram identificadas por amplificação da região r16S. Os genes SEA, SEE, SEC e SED foram detectados por amplificação PCR convencional utilizando primers específicos para cada gene, e os amplicons foram evidenciados com eletroforese. Resultados. Houve predomínio do grupo Staphylococcus coagulase positivo (65,2%) sobre o grupo negativo da coagulase (37,5%). Staphylococcus aureus foi a cepa mais frequente (88,5%). O gene SEA (1.7%) foi detectado em S. sciuri, o gene SEB (3.6%) em S. pasteuri e S. warneri, SEC (3.6%) em S. sciuri e SEC em S. saprophyticus. Os genes SED e SEE não foram detectados em nenhuma das cepas avaliadas. Conclusões. Os resultados confirmam que a mastite bovina também é causada por Staphylococcus coagulase-negativo, o que indica a possibilidade de que este grupo adquira atributos genéticos, como enterotoxinas e fatores de virulência, por transferência horizontal.


Subject(s)
Animals , Enterotoxins , Staphylococcus , Polymerase Chain Reaction , Genes, vif , Mastitis
14.
Yonsei Medical Journal ; : 1190-1196, 2018.
Article in English | WPRIM | ID: wpr-718492

ABSTRACT

PURPOSE: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease. MATERIALS AND METHODS: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. The 16 patients who were finally included in the study were divided into three groups according to disease type: Kearns-Sayre syndrome (KSS), KSS-like, and chronic progressive external ophthalmoplegia (CPEO). RESULTS: The prevalences of clinical findings were as follows: ptosis and retinopathy, both over 80%; myopathy, including extraocular muscles, 75%; lactic acidosis, 71%; and elevated levels of serum creatine kinase, 47%. Half of the patients had normal magnetic resonance imaging findings. A biochemical enzyme assay revealed mitochondrial respiratory chain complex I defect as the most common (50%). The prevalence of abnormal muscle findings in light or electron microscopic examinations was 50% each, while that of large-scale mitochondrial DNA (mtDNA) deletions in a gene study was 25%. We compared the KSS and KSS-like groups with the CPEO patient group, which showed pigmentary retinopathy (p < 0.001), cardiac conduction disease (p=0.013), and large-scale mtDNA deletions (p=0.038). KSS and KSS-like groups also had gastrointestinal tract disorders such as abnormal gastrointestinal motility (p=0.013) unlike the CPEO group. CONCLUSION: Patients with KSS had gastrointestinal symptoms, which may indicate another aspect of systemic involvement. The presence of large-scale mtDNA deletions was an objective diagnostic factor for KSS and a gene study may be helpful for evaluating patients with KSS.


Subject(s)
Acidosis, Lactic , Classification , Creatine Kinase , Diagnosis , DNA, Mitochondrial , Electron Transport , Enzyme Assays , Gastrointestinal Motility , Gastrointestinal Tract , Genes, vif , Humans , Kearns-Sayre Syndrome , Magnetic Resonance Imaging , Mitochondrial Diseases , Muscles , Muscular Diseases , Ophthalmoplegia , Ophthalmoplegia, Chronic Progressive External , Prevalence , Retinitis Pigmentosa , Retrospective Studies
15.
Cancer Research and Treatment ; : 1203-1213, 2018.
Article in English | WPRIM | ID: wpr-717747

ABSTRACT

PURPOSE: This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). MATERIALS AND METHODS: RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. RESULTS: The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. CONCLUSION: CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.


Subject(s)
Cell Line , Colorectal Neoplasms , DNA Damage , Genes, vif , Humans , Neoplasm Metastasis , Polymerase Chain Reaction , Radiation Tolerance , Radiation, Ionizing , Radiotherapy , Rectal Neoplasms , RNA Interference , RNA, Messenger , Sequence Analysis, RNA , Therapeutic Uses
16.
Yonsei Medical Journal ; : 760-768, 2018.
Article in English | WPRIM | ID: wpr-716427

ABSTRACT

PURPOSE: To compare differentially expressed genes (DEGs) mediating osteoarthritis (OA) in knee cartilage and in normal knee cartilage in a rat model of OA and to identify their impact on molecular pathways associated with OA. MATERIALS AND METHODS: A gene expression profile was downloaded from the Gene Expression Omnibus database. Analysis of DEGs was carried out using GEO2R. Enrichment analyses were performed on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway using the Search Tool for the Retrieval of Interacting Genes database (http://www.string-db.org/). Subsequently, the regulatory interaction network of OA-associated genes was visualized using Cytoscape software (version 3.4.0; www.cytoscape.org). RESULTS: In the gene expression profile GSE103416, a total of 99 DEGs were identified. Among them, 76 DEGs (76.77%) were overexpressed, and the remaining 23 DEGs (23.23%) were underexpressed. GO and pathway enrichment analyses of target genes were performed. Using gene-gene interaction network analysis, relevant core genes, including MET, UBB, GNAI3, and GNA13, were shown to hold a potential relationship with the development of OA in cartilage. Using quantitative real-time PCR, the Gna13/cGMP-PKG signaling pathway was identified as a potential research target for therapy and for further understanding the development of OA. CONCLUSION: The results of the present study provide a comprehensive understanding of the roles of DEGs in knee cartilage in relation to the development of OA.


Subject(s)
Animals , Cartilage , Gene Expression Profiling , Gene Expression , Gene Ontology , Genes, vif , Genome , Knee , Models, Animal , Negotiating , Osteoarthritis , Rats , Real-Time Polymerase Chain Reaction , Transcriptome
17.
Article in English | WPRIM | ID: wpr-728571

ABSTRACT

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colonderived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.


Subject(s)
Animals , Carcinogenesis , Cell Line , Colon , Colonic Neoplasms , Fibroblasts , Genes, vif , HCT116 Cells , Heterografts , Humans , In Vitro Techniques , Mice , Reactive Oxygen Species
18.
Genomics & Informatics ; : 56-64, 2017.
Article in English | WPRIM | ID: wpr-93440

ABSTRACT

We have previously reported that NS-398, a cyclooxygenase-2 (COX-2)–selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2–selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment. NS-398 up-regulated gene sets involved in the tumor necrosis factor β receptor pathway and the fructose and mannose metabolism, whereas it down-regulated a gene set involved in protein secretion. Celecoxib up-regulated gene sets involved in G2M checkpoint and E2F targets. Aspirin up-regulated the gene set involved in protein secretion, and down-regulated gene sets involved in RNA transcription. These results suggest that COX inhibitors modulate cellular senescence by different mechanisms and will provide useful information to understand senescence-modulating mechanisms of COX inhibitors.


Subject(s)
Aging , Animals , Aspirin , Celecoxib , Cellular Senescence , Cyclooxygenase 2 , Fibroblasts , Fructose , Gene Expression , Genes, vif , Humans , Mannose , Metabolism , Mice , Mice, Hairless , Oligonucleotide Array Sequence Analysis , RNA , Skin Aging , Tumor Necrosis Factor-alpha
19.
Article in English | WPRIM | ID: wpr-175104

ABSTRACT

OBJECTIVE: The mGluR1 (metabotropic glutamate receptor 1) gene, a G protein–coupled receptor, is known to mediate perceptions of umami tastes. Genetic variation in taste receptors may influence dietary intake, and in turn have an impact on nutritional status and risk of chronic disease. We investigated the association of mGluR1 rs2814863 polymorphism with lipid profiles and cardiovascular disease (CVD) risk, together with their modulation by macronutrient intake in Korean adults. METHODS: The subjects consisted of 8,380 Koreans aged 40-69 years participating in the Anseong and Ansan Cohort Study, which was a part of the Korean Genome Epidemiology Study (KoGES). Data was collected using self-administered questionnaires, anthropometric measurements, and blood chemical analysis. RESULTS: Carriers of C allele at mGluR1 rs2814863 was associated with decreased high density lipoprotein cholesterol (HDL-C) and increased triglyceride as compared to carriers of TT. Also, carriers of the C allele showed higher fat intake and lower carbohydrate intake than those with carriers of TT. After adjustment for multiple testing using false-discovery rate method, the significant difference of HDL-C, triglyceride, dietary fat, and carbohydrate across genotypes disappeared. Gene-diet interaction effects between rs2814863 and macronutrients intake were not significantly associated with HDL-C and triglyceride levels. However, carriers of C allele demonstrated significantly higher odds of CVD {odds ratio=1.13, 95% CI=1.02-1.25} compared with carriers of TT. CONCLUSIONS: Our findings support significant associations between the mGluR1 rs2814863 genotype and CVD-related variables in Korean adults. However, these associations are not modified by macronutrient intake.


Subject(s)
Adult , Alleles , Blood Chemical Analysis , Cardiovascular Diseases , Cholesterol, HDL , Chronic Disease , Cohort Studies , Dietary Fats , Epidemiology , Genes, vif , Genetic Variation , Genome , Genotype , Humans , Methods , Nutritional Status , Polymorphism, Single Nucleotide , Receptors, Glutamate , Receptors, Metabotropic Glutamate , Triglycerides
20.
Article in Korean | WPRIM | ID: wpr-180212

ABSTRACT

With an aging population and the development of surgical techniques, there is a growing demand for bone reconstruction in areas of trauma, arthroplasty, and spinal fusion Although autogenous bone grafting may be the best method for stimulating bone repair and regeneration, there are still problems and complications, including morbidity related to bone harvesting and limitation of harvest amount. Allogeneic bone grafts have a limited supply and risk of transmission of infectious diseases. Over the past several decades, the use of bone substitutes, such as calcium phosphate, has increased; however, they have limited indications. Biomedical research has suggested a possibility of stimulating the self-healing mechanism by locally transmitting the external growth factors or stimulating local production through a gene transfer. In this review, we evaluate recent advances, including bone graft, bone substitutes, and tissue engineering.


Subject(s)
Aging , Allografts , Arthroplasty , Bone Substitutes , Bone Transplantation , Calcium , Communicable Diseases , Genes, vif , Intercellular Signaling Peptides and Proteins , Methods , Regeneration , Spinal Fusion , Tissue Engineering , Transplants
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