RESUMEN
BACKGROUND: Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma. METHODS: Forty-three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan-Meier method, Cox regression analysis and the log-rank test. RESULTS: The 1-year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1-year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1-year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression-free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low-grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high-grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low-grade glioma. CONCLUSIONS: Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis.
Asunto(s)
Neoplasias Encefálicas/genética , Predisposición Genética a la Enfermedad/genética , Glioma/genética , Polimorfismo de Nucleótido Simple , Ácido Anhídrido Hidrolasas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Proteínas de Unión al ADN/genética , Frecuencia de los Genes , Genotipo , Glioma/patología , Glioma/terapia , Humanos , Estimación de Kaplan-Meier , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
The expression of transcription-induced chimeras (TICs) was underestimated due to strategic and logical reasons. In order to thoroughly examine TICs, systematic survey of TIC events was conducted in mammalian genomes using ESTs, followed by experimental validation using RT-PCR and real-time quantitative PCR (qPCR). The expression of â¼98% TIC events in at least one tissue or cell line from both mouse and human was verified. Besides, â¼40% TICs were broadly expressed, and â¼33% of TICs showed expression levels comparable to or higher than their upstream parental genes. We further identified putative chimeric proteins in public databases and validated two using Western blotting. GO analysis revealed that proteins resided in one multi-protein complex or functioning in metabolic or signaling pathway tended to produce fused products. Taken together, we have shown substantial evidence for the underestimated TIC events; and TICs could be a novel regulated way to further increases the proteome complexity in mammalian genomes. Possible regulation mechanisms and evolution of TICs were also discussed.
Asunto(s)
Empalme Alternativo/genética , Etiquetas de Secuencia Expresada , Regulación de la Expresión Génica/genética , Genoma/genética , Proteoma/genética , Transcripción Genética/genética , Animales , Mapeo Cromosómico/métodos , Humanos , RatonesRESUMEN
BACKGROUND The epithelial-mesenchymal transition (EMT) has been shown to be involved in the process of invasion and metastasis of prostate cancer. SIRT1 is the mammalian homologue of the silent information regulator 2 (Sir2) gene, and is abnormally expressed in prostate cancer cells. Therefore, it is hypothesized that SIRT1 mediates the invasion/metastatic ability of prostate cancer via EMT regulation. This study thus investigated the effect of SIRT1 gene on the invasion and migration of prostate cancer cell line PC-3 via the small interference RNA (siRNA) against SIRT1. MATERIAL AND METHODS SiRNA construct was transfected into PC-3 cells, which were tested for the cell migration and invasion ability by scratch assay and Transwell migration assay, respectively. Expression levels of vimentin, E-cadherin, and N-cadherin were further quantified by Western blotting and RT-PCR. RESULTS Both mRNA and protein levels of SIRT1 were depressed after siRNA transfection, along with weakened migration and invasion ability of PC-3 cells. Elevated E-cadherin and suppressed N-cadherin and vimentin were observed in those transfected cells. CONCLUSIONS The silencing of SIRT1 gene in PC-3 cells can suppress the movement, migration, and invasion functions of prostate cancer cells, possibly via the down-regulation of mesenchymal markers vimentin and N-cadherin accompanied with up-regulation of epithelial marker N-cadherin, thus reversing the EMT process.
Asunto(s)
Transición Epitelial-Mesenquimal/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Celulosa 1,4-beta-Celobiosidasa/metabolismo , Regulación hacia Abajo , Humanos , Masculino , Neoplasias de la Próstata/patología , ARN Interferente Pequeño , Transfección , Regulación hacia Arriba , Vimentina/metabolismoRESUMEN
BACKGROUND: Anti-CD47 monoclonal antibodies have increasing clinical applications in the treatment of cancer. However, anti-CD47 monoclonal antibodies interfere with immunohematology testing in patients who require blood transfusion. As the current approaches to removing any interferences have technical problems, new methods need to be developed to resolve anti-CD47 interference in immunohematology testing. MATERIALS AND METHODS: We evaluated the Daudi cell line for the adsorption of free anti-CD47 monoclonal antibodies from patients' plasma to facilitate immunohematology testing in patients treated with anti-CD47 monoclonal antibody. CD47 expression was identified on the Daudi cells using flow cytometry and confocal microscopy. Next, we tested the ability of intact Daudi cells mixed with simulating plasma and clinical samples to achieve efficient removal of interfering anti-CD47 monoclonal antibodies. The indirect antiglobulin test was used to verify whether interference from anti-CD47 monoclonal antibodies in plasma was eliminated and whether the detection of other irregular antibodies was affected. The effect of eliminating interference was also investigated in relation to the time that the Daudi cells were stored after having been fixed with paraformaldehyde. RESULTS: CD47 expression was higher on Daudi cells than on red blood cells. Analysis of the indirect antiglobulin test results revealed that anti-CD47 monoclonal antibody-treated patients' plasma absorbed by Daudi cells for 15 min at 37°C could completely prevent the interference of anti-CD47 monoclonal antibodies in immunohematology testing while the detection of the tested antibodies, including anti-D and anti-K, was unaffected. DISCUSSION: By decreasing the incubation time, we discovered that interferences in samples with agglutination strengths below 2+ could be eliminated after incubation for 5 min. Of importance, Daudi cells can be preserved with 4% paraformaldehyde for 14 days as short-term storage reagents. This is the first study in which Daudi cells were used to effectively resolve the interference of anti-CD47 monoclonal antibodies in pretransfusion tests.
Asunto(s)
Anticuerpos Monoclonales , Antígeno CD47 , Formaldehído , Polímeros , Humanos , Antígeno CD47/metabolismo , Transfusión Sanguínea , Eritrocitos/metabolismo , Anticuerpos Monoclonales HumanizadosRESUMEN
Breast cancer is the most common malignant tumor in women, which accounts for 6.9% of all cancer-related deaths. Early diagnosis is crucial for making the best clinical decision and improving the prognosis of patients. Circulating tumor cells (CTCs) have been regarded as significant tumor biomarkers. Herein, we designed a colorimetric biosensor for breast cancer CTCs quantification based on ladder-branch hybridization chain reaction (HCR) and DNA flowers/gold nanoclusters (DFs/AuNCs) nanozyme. With the assistance of complementary DNA labeled on magnetic beads (MBs), the cleavage products of RNA-cleaving DNAzymes (RCDs) could be rapidly captured, subsequently triggering ladder-branch HCR. In addition, the DFs/AuNCs nanozyme was applied for colorimetric analysis, which further improved the sensitivity for the detection of target CTCs. Benefiting from specific RCDs, ladder-branch HCR and DFs/AuNCs, we achieved a superior detection limit of 3 cells/mL as well as a broad linear range of 10 cells/mL to 104 cells/mL. Conclusively, this colorimetric biosensor achieved sensitively and selectively detection of breast cancer CTCs without the participation of enzymes at room temperature, which might provide new insight into the early detection of breast cancer.
Asunto(s)
Neoplasias de la Mama , Colorimetría , Oro , Nanopartículas del Metal , Células Neoplásicas Circulantes , Hibridación de Ácido Nucleico , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Humanos , Colorimetría/métodos , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico , Oro/química , Femenino , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos , ADN Catalítico/química , ADN Catalítico/metabolismo , Límite de Detección , Células MCF-7RESUMEN
Background: Studies have been inconclusive on the risk for hemorrhage in patients with a history of aspirin use who underwent emergency external ventricular drainage (EVD)/intracranial pressure (ICP) probe placement. The aim of this study was to explore hemorrhage-related risk factors in order to reduce the risk for hemorrhage in these patients. Methods: Between July 2014 and July 2020, patients were retrospectively divided into EVD/ICP-related hemorrhage and non-hemorrhage groups. The collected data included age, gender, major diagnosis, medical history, imaging examinations, conventional coagulation test data, thromboelastography with platelet mapping (TEG-PM), surgical procedures and discharge conditions. Results: In total 94 patients, 21 in the hemorrhage group (15 males, 6 females) and 73 in the non-hemorrhage group (52 males, 21 females) were included. The majority of hemorrhages were recorded in EVD patients (19/21; 90.5%). Platelet AA pathway inhibition rate of ≥75% (sensitivity: 79.45% specificity: 52.38%) (P = 0.014) and SBP ≥125 mmHg (P = 0.006) were significantly related to hemorrhage. When the platelet AA pathway inhibition rate was ≥75% and the during-procedure SBP was ≥125 mmHg, the hemorrhage rate was significantly higher (83.3%) than with SBP <125 mmHg (6.7%) (P < 0.001). When the inhibition rate was <75%, there were no significant differences in the hemorrhage rates between the during-procedure SBP ≥125 mmHg group (17.2%) and the SBP <125 mmHg group (13.2%) (P > 0.05). Multivariate logistic regression analysis revealed that a platelet AA pathway inhibition rate ≥75% (OR = 5.183, 95% CI: 1.683-15.960) and during-procedure SBP ≥125 mmHg (OR = 4.609, 95% CI: 1.466-14.484) were independent risk factors for EVD/ICP-related hemorrhage. Conclusion: Patients with long-term aspirin therapy, a platelet AA pathway inhibition rate ≥75% and during-procedure SBP ≥125 mmHg had a significantly higher risk of hemorrhage, which could be reduced by adjusting the SBP to <125 mmHg.
Asunto(s)
Empalme Alternativo , Antígenos Nucleares/genética , Proteínas Asociadas a Matriz Nuclear/genética , Sistemas de Lectura Abierta/genética , Reacción en Cadena de la Polimerasa/métodos , Secuencia de Bases , Proteínas de Ciclo Celular , Cartilla de ADN/genética , Células HeLa , Humanos , Isoformas de Proteínas/genética , Análisis de Secuencia de ADNRESUMEN
HCV is prevailed in the world as well as in China. Blood transfusion is one of the most common transmission pathways of this pathogen. Although data of HCV infection character were reported during the past years, anti-HCV reactive profile of China donors was not fully clear yet. Furthermore, infection progress was found related to the HCV genotype. Different genotype led to different efficacy when interferon was introduced into HCV therapy. Here we provided character data of HCV infection in China blood donors from the year of 2000 to 2009. The infection rate in local donors was lower than general population and descended from 0.80% to 0.40% or so in recent years. About 83% HCV strains were categorized into genotypes 1b and 2a. But 1b subtype cases climbed and 2a subtype cases decreased. The current study threw more light on HCV infection of blood donors in China, at least in the Northern region.
Asunto(s)
Donantes de Sangre , Hepacivirus/aislamiento & purificación , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Hepatitis C/virología , China/epidemiología , Ensayo de Inmunoadsorción Enzimática , Genotipo , Hepacivirus/genética , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estudios SeroepidemiológicosRESUMEN
Because no vaccine or effective therapy is available, thousands of people with HCV have died in recent years. Cytotoxic T lymphocytes (CTLs) play a critical role in the host cellular immune response against HCV. CTL epitopes in HCV core protein have been identified and used in vaccine development. T helper epitopes could promote cytokine secretion and antibody production to fight HCV. Tetanus toxin, an immunogen with many T helper epitopes, was once used in HBV therapeutic vaccine design. Here, eukaryotic and prokaryotic expression vectors were constructed to express truncated fragments of tetanus toxin and core genes of HCV. HLAA2.1 transgenic mice were inoculated with a recombinant plasmid vehicle with these two heterogenic gene fragments, and this augmented the titres of antibody against HCV. Antigen-specific lymphocyte proliferation, Th1 and Th2 cytokine levels and the number of lysed cells were markedly increased in the combined immunization group compared to controls. These findings provide new insights into a potential role for T helper epitopes from tetanus toxin combined with protein from the HCV core gene, which has numerous CTL epitopes. This design strategy may aid in the development of new vaccines against HCV.
Asunto(s)
Hepacivirus/inmunología , Hepatitis C/prevención & control , Toxina Tetánica/inmunología , Vacunas Sintéticas/inmunología , Proteínas del Núcleo Viral/inmunología , Vacunas Virales/inmunología , Animales , Proliferación Celular , Ratones , Ratones Transgénicos , Proteínas Recombinantes , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/fisiología , Toxina Tetánica/química , Proteínas del Núcleo Viral/químicaRESUMEN
Epigenetic factors may modulate chronic Hepatitis B viral infection by affecting virion gene transcription. The aim of this study was to compare the methylation status of the intrahepatic covalently closed circular DNA (cccDNA) CpG island 2 and HBV replication capability. HBV cccDNA was extracted from liver biopsies of 55 HBsAg-positive patients with chronic hepatitis B (32 HBeAg-positive and 23 HBeAg-negative), and was analyzed for methylation status and quantity. The two Hpa II recognition sequences CCpGG in the CpG island 2 were methylated in infected liver tissues from 24 (43.6%) of 55 patients. Positive ratios of cccDNA methylation were significantly higher in HBeAg-negative patients (15/23, 65.2%) than HBeAg-positive patients (9/32, 28.1%) (P < 0.05). The percentage of methylated-cccDNA/total-cccDNA of HBeAg-negative samples (a median of 48%, ranging from 5% to 83%) was significantly higher (P < 0.001) than HBeAg-positive samples (a median of 14%, ranging from 0.26% to 35%). Ratios of relaxed circular DNA (rcDNA) to cccDNA molecules revealed that cccDNA methylation correlated with impaired virion productivity in HBeAg-positive individuals (P < 0.05). The bisulfite DNA sequencing showed that methylation density was significantly higher in HBeAg-negative than in HBeAg-positive patients (P < 0.05). The methylation level of the CpG island 2 of the cccDNA in HBeAg-negative patients was higher than that in HBeAg-positive patients, suggesting that HBV cccDNA methylation may be relevant to replication capability of HBV.
Asunto(s)
ADN Circular/metabolismo , ADN Viral/metabolismo , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/virología , Hígado/virología , Replicación Viral , Adulto , Anciano , Metilación de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Hepatitis B virus (HBV) is prevalent in China and screening of blood donors is mandatory. Up to now, ELISA has been universally used by the China blood bank. However, this strategy has sometimes failed due to the high frequency of nucleoside acid mutations. Understanding HBV evolution and strain diversity could help devise a better screening system for blood donors. However, this kind of information in China, especially in the northwest region, is lacking. In the present study, serological markers and the HBV DNA load of 11 samples from blood donor candidates from northwest China were determined. The HBV strains were most clustered into B and C genotypes and could not be clustered into similar types from reference sequences. Subsequent testing showed liver function impairment and increasing virus load in the positive donors. This HBV evolutionary data for China will allow for better ELISA and NAT screening efficiency in the blood bank of China, especially in the northwest region.
Asunto(s)
Donantes de Sangre , Evolución Molecular , Virus de la Hepatitis B/genética , Hepatitis B/sangre , Adulto , China , Femenino , Genotipo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Serotipificación , Adulto JovenRESUMEN
OBJECTIVE: To construct PEGylated trichosanthin (TCS) mutein and analyze its bioactivities, immunogenicity, acute toxicity, and pharmacokinetics. METHODS: The potential antigenic determinant site YFF81-83 in the molecule of TCS was selected to undergo site-directed mutagenesis. Thus, a TCS mutein named TCS(YFF81-83ACS) was constructed and expressed in Escherichia coli of the line BL21 (DE3). Wild TCS (wTCS), TCSY(FF81-83ACS), and PEGylated TCS(YFF81-83ACS) (PEG- TCS(YFF81-83ACS)) of different concentrations were incubated with the supercoiled plasmid pUC19 to detect the DNAse activity, mixed with rabbit reticulocyte lysate to detect the ribosome inactivation activity, subcutaneously injected into 6 mice respectively to measure the serum IgG and IgE levels, intravenously injected into mice to observe the toxicity, and intravenously injected into SD rats to observe its -plasma half-life. RESULTS: The DNAse activity of the PEG-TCS(YFF81-83ACS) was similar to that of the wTCS. The ribosome inactivation activity of the PEG-TCS(YFF81-83ACS) was 1/9-1/8 of that of the wTCS (P < 0.05). The serum IgE and IgG levels of the PEG-TCS(YFF81-83ACS) were both significantly lower than those of the wTCS (both P < 0.05). The LD50 of the PEG-TCS(YFF81-83ACS) was 1.8 times that of the wTCS (P < 0.05). The mean residence time and plasma half-life of the PEG-TCS(YFF81-83ACS) were significantly increased and its plasma clearance was significantly decreased (all P < 0.05). CONCLUSION: Site-directed mutagenesis and PEGylation of TCS provide a new approach for reconstructing TCS.
Asunto(s)
Proteínas Mutantes/inmunología , Proteínas Mutantes/toxicidad , Polietilenglicoles/química , Tricosantina/genética , Animales , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Ratones , Ratones Endogámicos BALB C , Mutagénesis Sitio-Dirigida , Proteínas Mutantes/farmacocinética , Mutación Puntual , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad Aguda , Tricosantina/sangre , Tricosantina/químicaRESUMEN
Autoimmune diseases (ADs) arise from an abnormal immune response of the body against substances and tissues normally present in the body. More than a hundred of ADs have been described in the literature so far. Although their etiology remains largely unclear, various types of ADs tend to share more associated genes with other types of ADs than with non-AD types. Here we present GAAD, a gene and AD association database. In GAAD, we collected 44,762 associations between 49 ADs and 4249 genes from public databases and MEDLINE documents. We manually verified the associations to ensure the quality and credibility. We reconstructed and recapitulated the relationships among ADs using their shared genes, which further validated the quality of our data. We also provided a list of significantly co-occurring gene pairs among ADs; with embedded tools, users can query gene co-occurrences and construct customized co-occurrence network with genes of interest. To make GAAD more straightforward to experimental biologists and medical scientists, we extracted additional information describing the associations through text mining, including the putative diagnostic value of the associations, type and position of gene polymorphisms, expression changes of implicated genes, as well as the phenotypical consequences, and grouped the associations accordingly. GAAD is freely available at http://gaad.medgenius.info.
Asunto(s)
Enfermedades Autoinmunes/genética , Bases de Datos Factuales , Estudios de Asociación Genética , Minería de Datos , Redes Reguladoras de Genes , HumanosRESUMEN
An interested reader drew to the attention of the Editorial Board of Molecular Medicine Reports that certain data in the above paper had already been published in a previous study featuring several of the same authors [Zhang XQ, Huang XF, Hu XB, Zhan YH, An QX, Yang SM, Xia AJ, Yi J, Chen R, Mu SJ and Wu DC: "Apogossypolone, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro". Asian J Androl 12: 697-708, 2010]. Specifically, Figs. 2A and 5C were originally featured, either in their entirety or in part, as Figs 6C and 2G, respectively, in the Asian J Androl paper. Following an internal investigation, the Editorial Board was able to confirm that these data were published previously in the Asian J Androl paper, and therefore it has been decided that the above-mentioned paper should be retracted on account of the incidences of data sharing. The authors have agreed to this decision, and we apologize to the readership of the Journal for any inconvenience caused. [the original article was published in Molecular Medicine Reports 10: 1184-1194, 2014; DOI: 10.3892/mmr.2014.2379].
RESUMEN
Trichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) with multiple biological and pharmacological activities. It has been approved effective in the clinical treatment of AIDS and tumor, but its strong immunogenicity and short plasma half-life have limited the clinical administration. To reduce the immunogenicity and prolong the plasma half-life of this compound, three TCS muteins (M(1), M(2) and M(3)) and two PEGylated TCS muteins (PM(1) and PM(2)) were constructed by site-directed mutagenesis and PEGylation, respectively. Compared with the unmodified TCS, both PEGylated TCS showed a 3- to 4-fold decrease in immunogenicity, a 0.5- to 0.8-fold decrease in non-specific toxicity, and a 4.5- to 6-fold increase in plasma half-life. But there is a problem of activity reduction. The increased circulating half-life in vivo may compensate for the reduced activity. Together with the other benefits of PEGylation such as reduced immunogenicity and toxicity, it is worthwhile to further explore the potential application of the PEGylated TCS as a better therapeutic agent for AIDS and tumor.
Asunto(s)
Polietilenglicoles/química , Proteínas Inactivadoras de Ribosomas/inmunología , Tricosantina/inmunología , Animales , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/inmunología , Fármacos Anti-VIH/farmacología , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/inmunología , Antineoplásicos Fitogénicos/farmacología , Ratones , Ratones Endogámicos BALB C , Mutagénesis Sitio-Dirigida , Proteínas Inactivadoras de Ribosomas/efectos adversos , Proteínas Inactivadoras de Ribosomas/genética , Proteínas Inactivadoras de Ribosomas/farmacología , Tricosantina/efectos adversos , Tricosantina/genética , Tricosantina/farmacologíaRESUMEN
BACKGROUND: Several genome-wide association studies of primary biliary cirrhosis (PBC) in European and Japanese origins have shown significant association of dozens of genetic loci contributive to the susceptibility of PBC. Most of the loci were related to immune response pathway. In this study, we tested whether the lipid metabolic gene HELZ2 was associated with the pathogenesis of PBC. METHODS: In 586 PBC cases (358 in case 1 group and 201 in case 2 group) and 726 healthy controls of Chinese Han, six nonsynonymous SNPs were genotyped by MassArray iPLEX. The same control were used for the two groups of PBC cases. Allele frequencies were calculated by χ(2) test based on 2 × 2 contingency tables. All data were analyzed using the PLINK tool set. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated, and p values (corrected for multiple testing by Bonferroni adjustment) less than 0.05 were considered statistically significant. RESULTS: The A allele of rs79267778 was significantly associated with PBC (ORcombined = 4.204 [1.670-10.582], p combined = 1.87E-04). It changed the amino acid at position 1904 (NM_001037335) from Threonine (ACG) to Methionine (ATG). This site was highly conserved in mammals and predicted to be POSSIBLY DAMAGING with a score of 0.469 by PolyPhen-2. It's further predicted that T1904 M could INCREASE the protein stability with a confidence at 25.18 % under the condition of pH 7.0 and 37 °C. CONCLUSION: The result was the first time to show evidence of the lipid metabolic gene HELZ2 related to autoimmune disease, at least in PBC of Chinese Han.
RESUMEN
Genome-wide association studies in European individuals have revealed that IL12A is strongly associated with primary biliary cirrhosis (PBC). However, this association was not detected in replicative studies conducted in Chinese Han and Japanese populations.To verify contributions of genetic variants of IL12A to the pathogenesis of PBC in Chinese populations, a replicative study of 22 single nucleotide polymorphisms (SNPs) around the IL12A gene locus was performed in a cohort of 586 PBC cases and 726 healthy controls. Three out of the 22 SNPs were significantly associated with PBC. The 2 SNPs with the most significant association signal were rs4679868 (Pâ=â6.59E-05, odds ratio [OR]â=â1.554 [1.253-1.927]) and rs6441286 (Pâ=â8.00E-05, ORâ=â1.551 [1.250-1.924]). These 2 SNPs were strongly linked to each other (râ=â0.981), and both were found to be significantly associated with PBC in European populations.An expression quantitative trait loci (eQTL) analysis was performed based on the observation that these 2 SNPs were located in proximity to 2 enhancers verified by luciferase reporter systems in the HEK293 cell line. The results of eQTL analysis, conducted using the publically accessible data, showed that the risk alleles of rs4679868 and rs6441286 were significantly associated with decreased expression of IL12A in lymphoblastoid cell lines derived from individuals of Chinese Han ancestry (Pâ=â0.0031 for rs4679868 and Pâ=â0.0073 for rs6441286). In addition, the risk alleles of the 2 SNPs were significantly associated with down-regulation of SCHIP1, a celiac disease susceptible gene, 91.5âkb upstream of IL12A.These results not only demonstrated that IL12A is associated with PBC in the Chinese Han population but also identified a potential mechanism for its involvement in the pathogenesis of PBC.
Asunto(s)
Pueblo Asiatico/genética , Subunidad p35 de la Interleucina-12/sangre , Cirrosis Hepática Biliar/genética , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Proteínas Portadoras/metabolismo , Estudios de Casos y Controles , Niño , China , Regulación hacia Abajo , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo , Células HEK293 , Humanos , Cirrosis Hepática Biliar/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
AIM: To establish nested-PCR methods for the detection of SENV-D and SENV-H and to investigate the epidemiology of SEN virus in China. METHODS: According to published gene sequences, primers from the conserved region were designed. Then, 135 samples from healthy voluntary blood donors and 242 samples from patients with various forms of liver disease were detected by nested-PCR of SENV-D/H. Some PCR products were cloned and sequenced. RESULTS: By sequencing, the specificity of genotype-specific PCR was confirmed. SENV-D/H DNA was detected in 31% of the blood donors, which was higher than those in America and Italy (2%), and in Japan and Taiwan (15-20%). The prevalence of SENV-D/H viremia was significantly higher in patients with hepatitis B and hepatitis C than in blood donors (59-85% vs 31%, P<0.05). The prevalence among patients with non-A-E hepatitis was significantly higher than among blood donors (68% vs 31%, P<0.01), and equivalent to that among patients with hepatitis B and C. CONCLUSION: Nested-PCR with genotype-specific primers could serve as a useful SENV screening assay. SENV has the same transmission modes as HBV and HCV. The high prevalence in patients with non-A-E hepatitis may attribute to the transmission modes, and SENV may not serve as the causative agents.
Asunto(s)
Infecciones por Virus ADN/epidemiología , Virus ADN/aislamiento & purificación , Hepatopatías/epidemiología , Donantes de Sangre/estadística & datos numéricos , China , Infecciones por Virus ADN/complicaciones , Virus ADN/clasificación , Virus ADN/genética , Hepatitis A/complicaciones , Hepatitis A/epidemiología , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Humanos , Hepatopatías/virología , Filogenia , Reacción en Cadena de la Polimerasa/métodos , PrevalenciaRESUMEN
The aim of the present study was to investigate the antitumor effect of apogossypolone (ApoG2) on human LNCaP cells in vitro and in vivo. Cell viability was evaluated using an MTT assay. Cell autophagy and apoptosis were detected by flow cytometry and using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively. Morphological autophagy alterations were observed by transmission electron microscopy. The formation of acidic vesicular organelles was assessed by acridine orange staining and fluorescence microscopy. Quantitative polymerase chain reaction (qPCR) was conducted to detect the expression levels of apoptosisassociated protein Bcell lymphoma 2 (Bcl2) and Bak. The models of transplantation tumors in nude mice were established via subcutaneous injection of LNCaP cells. Growth of LNCaP cells was inhibited by ApoG2 treatment. Flow cytometry demonstrated that ApoG2 induced apoptosis in LNCaP cells. The Bcl2 expression was decreased while Bak expression was increased. In addition, activation of cysteine aspartate protease (caspase)3 and 8 was observed and 3methyladenine (3MA) enhanced apoptosis of LNCaP cells. Furthermore, nude mice treated with ApoG2 demonstrated a significant decrease in tumor volume and a significant increase in cell viability. Immunohistochemical analysis of tumor tissues demonstrated that ApoG2 enhanced caspase3, 8, LC3B and beclin1 expression and reduced the expression of Bcl2. ApoG2 was able to effectively suppress the growth of LNCaP cells through the induction of autophagy and apoptosis.
Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Gosipol/análogos & derivados , Adenina/análogos & derivados , Adenina/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/efectos de los fármacos , Beclina-1 , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 8/genética , Caspasa 8/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Gosipol/farmacología , Humanos , Etiquetado Corte-Fin in Situ , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Electrónica de Transmisión , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína Destructora del Antagonista Homólogo bcl-2/genética , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismoRESUMEN
This study was conducted to examine the prevalence of syphilis among blood donors in the Xi'an region of China. All blood donors were unremunerated volunteers recruited from 2006 to 2010. Anti-Treponema pallidum and anti-HIV serology responses were determined using ELISA kits. Among 159 902 voluntary blood donors tested, a total of 575 syphilis (0.36%) and 55 HIV (0.03%) infections were identified. While an increasing trend was shown for the prevalence of both syphilis and HIV over the 5-year period, there was no statistical correlation between the two infections. Our results indicate that syphilis and HIV infections are increasing risk factors for the spread of blood-borne infections. Further investigations and improvements in blood collection and testing procedures are needed to help ensure the safety of donated blood in China.