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Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.
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Carcinoma Hepatocelular , Ictericia Obstructiva , Neoplasias Hepáticas , Trombosis , Femenino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagen , Ictericia Obstructiva/etiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Conducto Hepático Común/patología , Trombosis/diagnóstico por imagen , Trombosis/complicaciones , Hemorragia/complicacionesRESUMEN
BACKGROUND: Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis. AIM: To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy. METHODS: We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics. RESULTS: Our results revealed that FDX1, LIAS, and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1, LIAS, MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1, LIAS, and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map. CONCLUSION: In conclusion, FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy.
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To sort out the existing problems within the published 35 evidence-based acupuncture-moxibustion clinical practice guidelines (group standards) in Chinese: the development methods and the development process are not clear and strict enough; the evidence evaluation system fails to fully reflect the characteristics of acupuncture and moxibustion. Therefore, Norms for Formulation and Evaluation of the Guidelines on Clinical Practice of Acupuncture-Moxibustion, should require the guideline developers to consider the characteristics of acupuncture discipline, evaluate modern literature evidence comprehensively, and integrate ancient literature and medical experts' experience, to form proper recommendations for clinical practice. Specific requirements should be made simultaneously in the development process to make it clearer and stricter.
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Terapia por Acupuntura , Acupuntura , Moxibustión , China , Práctica Clínica Basada en la EvidenciaRESUMEN
BACKGROUND: Preventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients. METHODS: A total of 1,487 schizophrenia patients were included who were 18-65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors. RESULTS: The χ2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs. <3000 RMB: 28.6 vs. 42.4%, χ2 = 6.30, p = 0.036). The overall positive predictive value (PPV) of the logistic regression was 0.740, and the decision-tree model was 0.726. Both models were reliable. CONCLUSIONS: For schizophrenic patients discharged from hospital, who had good medication adherence, more higher household income, be employed and normal ability of daily living, would be less likely to relapse. Decision tree provides a new path for doctors to find the schizophrenic inpatient's relapse risk and give them reasonable treatment suggestions after discharge.
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LncRNA plasmacytoma variant translocation 1 (PVT1) has been recognized as an oncogenic lncRNA, which participates in the migration and invasion of many kinds of cancer cells and the development of cancers. In the present study, we explored its clinical significance and prognostic value in muscle invasive bladder cancer (MIBC).A total of 98 MIBC patients' samples were collected, who had undergone radical cystectomy from the March 2013 to December 2018. The associations between PVT1 expression and clinical data were calculated using the Chi-test. Overall survival curves were determined by the Kaplan-Meier technique and contrasted via log-rank test. We utilized univariate and multivariate Cox proportional hazard models to examine the HR and 95% CI.The expression levels of PVT1 were significantly higher in MIBC tissues than that in normal bladder tissues (Pâ<â.001). PVT1 expression was significantly correlated with tumor grade (Pâ=â.009), margin (Pâ=â.002), T stage (Pâ=â.02), and lymph node metastasis (Pâ<â.001). MIBC patients with high PVT1 expression level had shorter overall survival than those with low PVT1 expression level (log-rank test, Pâ=â.004). Multivariate Cox regression analysis showed that PVT1 expression level (HRâ=â2.381, 95% CI: 1.821-7.012, Pâ=â.014) was an independent factor in predicting the overall survival of MIBC patients.In summary, increased PVT1 expression in MIBC patients is correlated with a higher MIBC stage and is significantly associated with poor prognosis for MIBC patients, which may provide new insights into new therapeutic strategy and postoperative intervention against bladder cancer.
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ARN Largo no Codificante/biosíntesis , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Biomarcadores de Tumor , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Regulación hacia ArribaRESUMEN
To investigate effects of agomelatine and mirtazapine on sleep disturbances in patients with major depressive disorder. A total of 30 depressed patients with sleep disturbances, 27 of which completed the study, took agomelatine or mirtazapine for 8 weeks. Subjective scales were administered, and polysomnography was performed at baseline and at the end of week 1 and 8. Functional magnetic resonance imaging was performed at baseline and at the end of week 8. Compared with baseline, scores on the Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Sleep Dysfunction Rating Scale, and Insomnia Severity Index after 8 weeks of treatment significantly decreased in both groups, with no significant differences between groups, accompanied by significant increases in total sleep time, sleep efficiency, and rapid eye movement (REM) sleep and significant decrease in wake after sleep onset. Mirtazapine treatment increased N3 sleep at week 1 compared with agomelatine treatment, but this difference disappeared at week 8. The increases in the percentage and duration of N3 sleep were positively correlated with increases in connectivity between right dorsal lateral prefrontal cortex (dlPFC) and right precuneus and between left posterior cingulate cortex and right precuneus in both groups, respectively. Functional connectivity (FC) between right dlPFC and left precuneus in mirtazapine group was higher compared with agomelatine group after 8 weeks of treatment. These findings indicated that both agomelatine and mirtazapine improved sleep in depressed patients, and the effect of mirtazapine was greater than agomelatine with regard to rapidly increasing N3 sleep and gradually improving FC in the brain.
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Trastorno Depresivo Mayor , Acetamidas , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Humanos , Mirtazapina , Sueño , Resultado del TratamientoRESUMEN
PURPOSE: To investigate the occurrence and genetic characteristics of the bla IMP-26-positive plasmid from a multidrug-resistant clinical isolate, Enterobacter hormaechei L51. METHODS: Species identification was determined by MALDI-TOF MS and Sanger sequencing. Antimicrobial susceptibility testing was performed by the agar dilution and broth microdilution. Whole-genome sequencing was conducted using Illumina HiSeq 4000-PE150 and PacBio Sequel platforms, and the genome was annotated by the RAST annotation server. The ANI analysis of genomes was performed using OAT. Phylogenetic reconstruction and analyses were performed using the Harvest suite based on the core-genome SNPs of 61 publicly available E. hormaechei genomes. RESULTS: The E. hormaechei L51 genome consists of a 5,018,729 bp circular chromosome and a 343,918 bp conjugative IncHI2/2A plasmid pEHZJ1 encoding bla IMP-26 which surrounding genetic context was intI1-bla IMP-26-ltrA-qacE∆1-sul1. A new sequence type (ST1103) was assigned for the isolate L51 which was resistant to cephalosporins, carbapenems, but sensitive to piperacillin-tazobactam, amikacin, tigecycline, trimethoprim-sulfamethoxazole and colistin. Phylogenetic analysis demonstrated that E. hormaechei L51 belonged to the same subspecies as the reference strain E. hormaechei SCEH020042, however 18,248 divergent SNP were identified. Resistance genes in pEHZJ1 including aac(3)-IIc, aac(6') -IIc, bla SHV-178, bla DHA-1, bla TEM-1, bla IMP-26, ereA2, catII, fosA5, qnrB4, tet(D), sul1 and dfrA19. CONCLUSION: In our study, we identified a conjugative IncHI2/2A plasmid carrying bla IMP-26 and bla SHV-178 in E. hormaechei ST1103, a novel multidrug-resistant strain isolated from China, and describe the underlying resistance mechanisms of the strain and detailed genetic context of mega plasmid pEHZJ1.
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OBJECTIVE: To carry out the methodological quality evaluation and content analysis of the evidence-based clinical practice guidelines for acupuncture-moxibustion in China, and to provide reference for the development and updating of future guidelines. METHODS: With Appraisal of Guidelines for Research and Evaluationâ ¡(AGREEâ ¡), 20 evidence-based clinical practice guidelines for acupuncture and moxibustion in China were evaluated from six aspects: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence. In addition, the contents of 20 guidelines were systematically analyzed, and the characteristics of guidelines were summarized from the aspects of disease selection, operation technology type and safety. RESULTS: The scores of six domains were scope and purpose (91.1%), stakeholder involvement (68.5%), rigour of development (68.6%), clarity of presentation (90.3%), applicability (34.5%) and editorial independence (16.7%). The recommendations of the 20 acupuncture guidelines covered common clinical problems such as diagnosis, treatment and precautions, which were in line with the clinical characteristics of acupuncture and moxibustion in terms of content structure. CONCLUSION: The methodology of the evidence-based clinical practice guidelines for acupuncture and moxibustion in China conformed to the requirements of AGREEâ ¡ on the quality evaluation, and the overall quality was moderate, but the aspects of applicability and editorial independence were still needed to be improved. The contents of recommendations in 20 guidelines were specific and clear, in line with the characteristics of acupuncture and moxibustion, presenting clinical reference value. In the future, in the process of guideline development, the method of developing acupuncture and moxibustion guidelines should be constantly improved to improve the quality of the guidelines; in the meantime, more attention should be paid to the generalization and clinical applicability evaluation.
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Terapia por Acupuntura , Moxibustión , China , Medicina Basada en la Evidencia , Práctica Clínica Basada en la Evidencia , HumanosRESUMEN
BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.
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Antipsicóticos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Esquizofrenia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Agresión/efectos de los fármacos , China , Quimioterapia Combinada , Femenino , Humanos , Pacientes Internos/psicología , Pacientes Internos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , PolifarmaciaRESUMEN
The present study aimed to investigate the effects of astragaloside IV on osteoblastlike cell proliferation and migration, in addition to the underlying signaling pathway. In order to observe the effect on proliferation, a Cell Counting Kit8 assay and flow cytometry were used. To detect cell migration ability, cell scratch and Transwell cell migration assays were performed. The RNA and protein expression levels of hedgehog signaling molecules, including Sonic hedgehog (SHH) and GLI family zinc finger 1 (GLI1), were examined by reverse transcriptionquantitative polymerase chain reaction and western blot analyses. To inhibit the hedgehog signaling pathway, cyclopamine was used. Astragaloside IV, at a dosage of 1x102 µg/ml in MG63 cells and 1x103 µg/ml in U2OS cells, resulted in the enhanced proliferation and migration of cells, and the gene expression levels of the SHH and GLI1 were significantly increased. The combination of astragaloside IV and cyclopamine reduced MG63 and U2OS cell proliferation and migration, and inhibited the gene expression of SHH and GLI1. Astragaloside IV enhanced the proliferation and migration of human osteoblastlike cells through activating the hedgehog signaling pathway. The results of the present study provide a rational for the mechanistic link in astragaloside IV promoting the proliferation and migration of osteoblasts via the hedgehog signaling pathway.
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Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Proteínas Hedgehog/metabolismo , Osteoblastos , Saponinas/farmacología , Triterpenos/farmacología , Línea Celular Tumoral , Antagonismo de Drogas , Humanos , Terapia Molecular Dirigida , Oseointegración/efectos de los fármacos , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Alcaloides de Veratrum/farmacología , Proteína con Dedos de Zinc GLI1/metabolismoRESUMEN
PURPOSE: Previous studies have supported an association between serum insulin-like growth factor-1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients. RESULTS: HCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis (p = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92-3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81-2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761-2.260). MATERIALS AND METHODS: We conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients. CONCLUSIONS: Serum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.
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OBJECTIVE: To screen and identify serum biomarkers for childhood hepatoblastoma (HB). METHODS: The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. RESULTS: After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. CONCLUSIONS: Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.
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Apolipoproteína A-I/sangre , Biomarcadores/sangre , Detección Precoz del Cáncer , Hepatoblastoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Apolipoproteína A-I/genética , Preescolar , Femenino , Hepatoblastoma/sangre , Humanos , Lactante , Neoplasias Hepáticas/sangre , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Evidence indicates an increased cancer risk among type 2 diabetes mellitus (T2DM) patients, yet studies in mainland China are scarce. Based on Diabetes Surveillance System linking to Cancer Surveillance System of Zhejiang Province in China, we explored the cancer risk among T2DM patients. Totally, 327,268 T2DM patients were identified and followed from January 1, 2007 to December 31, 2013. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were reported. Overall cancer risk was found significantly increased with an SIR of 1.15 (95% CI 1.12-1.19) and 1.25 (95% CI 1.21-1.30) in males and females, respectively. Regarding specific cancer sites, risks of liver, colon, rectum, pancreas, and kidney were significantly increased with SIRs of 1.26 (95% CI 1.16-1.36), 1.47 (95% CI 1.29-1.67), 1.25 (95% CI 1.09-1.43), 2.81 (95% CI 2.50-3.16) and 1.61 (95% CI 1.28-2.03) in males, 1.53 (95% CI 1.35-1.73), 1.33 (95% CI 1.15-1.54), 1.29 (95% CI 1.10-1.51), 3.62 (95% CI 3.20-4.09) and 1.71 (95% CI 1.28-2.29) in females, respectively. A significant increased SIR was noted for prostate (1.80, 95% CI 1.58-2.06). Significant increased SIRs for lung (1.32, 95% CI 1.20-1.44) and stomach (1.16, 95% CI 1.03-1.30) were observed in females. We suggested an increased cancer risk among T2DM patients.
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Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Neoplasias/epidemiología , Neoplasias/etiología , Vigilancia de la Población , Riesgo , Anciano , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana EdadRESUMEN
Hrip1 is a novel hypersensitive response-inducing protein secreted by Alternaria tenuissima that activates defense responses and systemic acquired resistance in tobacco. This study investigates the role that Hrip1 plays in responses to abiotic and biotic stress using transgenic Arabidopsis thaliana expressing the Hrip1 gene under the control of the stress-inducible rd29A promoter or constitutive cauliflower mosaic virus 35S promoter. Bioassays showed that inducible Hrip1 expression in rd29Aâ·Hrip1 transgenic lines had a significantly higher effect on plant height, silique length, plant dry weight, seed germination and root length under salt and drought stress compared to expression in 35Sâ·Hrip1 lines and wild type plants. The level of enhancement of resistance to Botrytis cinerea by the 35Sâ·Hrip1 lines was higher than in the rd29Aâ·Hrip1 lines. Moreover, stress-related gene expression in the transgenic Arabidopsis lines was significantly increased by 200 mM NaCl and 200 mM mannitol treatments, and defense genes in the jasmonic acid and ethylene signaling pathway were significantly up-regulated after Botrytis inoculation in the Hrip1 transgenic plants. Furthermore, the activity of some antioxidant enzymes, such as peroxidase and catalase increased after salt and drought stress and Botrytis infection. These results suggested that the Hrip1 protein contributes to abiotic and biotic resistance in transgenic Arabidopsis and may be used as a useful gene for resistance breeding in crops. Although the constitutive expression of Hrip1 is suitable for biotic resistance, inducible Hrip1 expression is more responsive for abiotic resistance.
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Arabidopsis/genética , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Plantas Modificadas Genéticamente/genética , Alternaria/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/microbiología , Botrytis/patogenicidad , Sequías , Regulación de la Expresión Génica de las Plantas , Germinación/genética , Enfermedades de las Plantas/microbiología , Regiones Promotoras Genéticas , Estrés Fisiológico/genéticaRESUMEN
The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, the methylation epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is emerging as a common hallmark of different tumors. Here we showed that miR-433 and miR-127 were significantly down-regulated in gastric cancer (GC) tissues compared with the adjacent normal regions in 86 paired samples. Moreover, the lower level of miR-433 and miR-127 was associated with pM or pTNM stage in clinical gastric cancer patients. The restored expression of miR-433 and miR-127 in GC cells upon 5-Aza-CdR and TSA treatment suggested the loss of miR-433 and miR-127 was at least partly regulated by epigenetic modification in GC. Furthermore, the ectopic expression of miR-433 and miR-127 in gastric cancer cell lines HGC-27 inhibits cell proliferation, cell cycle progression, cell migration and invasion by directly interacting with the mRNA encoding oncogenic factors KRAS and MAPK4 respectively. Taken together, our results showed that miR-433 and miR-127 might act as tumor suppressors in GC, and it may provide novel diagnostic and therapeutic options for human GC clinical operation in the near future.
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MicroARNs/metabolismo , Neoplasias Gástricas/metabolismo , Regiones no Traducidas 3' , Adulto , Anciano , Anciano de 80 o más Años , Azacitidina/análogos & derivados , Azacitidina/toxicidad , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Decitabina , Regulación hacia Abajo , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Ácidos Hidroxámicos/toxicidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
OBJECTIVE: To investigate the role of heme oxygenase and carbon monoxide (HO/CO) in the development of spontaneous pain and hyperalgesia of rats induced by formalin injection. METHODS: Zinc protoporphyrin Znpp (the inhibitor of HO) was intrathecally injected to the rats with formalin inflammatory pain. Hemin (the agonist of HO) was intrathecally injected to the normal rats. The weighted pain scores were used to evaluate the degree of pain response. Thermal withdrawal latency and mechanical withdrawal threshold were observed to assess the degree of thermal hyperalgesia and mechanical allodynia. RESULTS: After the intrathecal injection of Znpp, the weighted pain score obviously reduced in a dose-dependent manner compared with the rats with formalin inflammatory pain. Intrathecal injection of Znpp had no obvious effect on thermal withdrawal latency and mechanical withdrawal threshold in injected feet compared with formalin group. But there was a prolongation in a dose-dependent manner in non injected feet. Intrathecal injection of Hemin to normal rats could shorten the thermal withdrawal latency and reduce the mechanical withdrawal threshold on both sides of hindpaws. CONCLUSION: Intrathecal injection of the HO inhibitor produced prominent inhibition to pain related behavior and thermal and mechanical hyperalgesia induced by formalin injection. Intrathecal injection of HO inductor could induce thermal and mechanical hyperalgesia in normal rats. The results indicated that HO/CO took part in the processes of spinal cord nociceptive information transmission and the development of thermal and mechanical hyperalgesia.
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Monóxido de Carbono , Hemo Oxigenasa (Desciclizante) , Hiperalgesia/inducido químicamente , Nociceptores/fisiología , Dolor/inducido químicamente , Animales , Formaldehído/efectos adversos , Hemo Oxigenasa (Desciclizante)/antagonistas & inhibidores , Hemina , Masculino , Nocicepción , Nociceptores/efectos de los fármacos , Protoporfirinas , Ratas , Ratas Sprague-DawleyRESUMEN
Xenorhabdus budapestensis can produce a variety of proteins that help this bacterium and its mutualistic nematode vector kill the host insect. In this report, we purified one protein fraction from the intracellular extract of X. budapestensis D43, which was designated HIP57. By injection, HIP57 caused Galleria mellonella larval bodies to blacken and die with an LD(50) of 206.81 ng/larva. Analyzes of HIP57 by two-dimensional gel electrophoresis showed that this protein was a single spot on the gel with a molecular weight of 57 kDa and a pI of â¼5. Sequencing and bioinformatic analysis suggested that the HIP57 toxin was homologous to GroEL. GroEL has been accepted as molecule chaperon; however, our research revealed that HIP57 (GroEL) possesses another novel function as an insecticide. A GroEL phylogenetic tree defined the relationship among the related species of mutualistic bacteria (Xenorhabdus and Photorhabdus) from the entomopathogenic nematodes and the evolution within the family Enterobacteriaceae. Thus, GroEL could be a complement to 16S rDNA for studying the molecular phylogenies of the family Enterobacteriaceae. Phenoloxidase (PO) activity analysis of G. mellonella larvae injected with HIP57 suggested that the toxin activates the PO cascade, which provides an extensive defense reaction that potentially responsible for G. mellonella larval death.
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Catecol Oxidasa/metabolismo , Chaperonina 60/genética , Chaperonina 60/metabolismo , Precursores Enzimáticos/metabolismo , Mariposas Nocturnas/microbiología , Xenorhabdus/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Proteínas Bacterianas/metabolismo , Chaperonina 60/aislamiento & purificación , Electroforesis en Gel Bidimensional , Activación Enzimática , Interacciones Huésped-Patógeno , Datos de Secuencia Molecular , Control Biológico de Vectores , Filogenia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de Proteína , Xenorhabdus/genéticaRESUMEN
Magnetic mesoporous carbonated hydroxyapatite microspheres have been fabricated hydrothermally by using CaCO(3)/Fe(3)O(4) microspheres as sacrificial templates. The high drug-loading capacity and sustained drug release property suggest that the multifunctional microspheres have great potentials for bone-implantable drug-delivery applications.
Asunto(s)
Carbonato de Calcio/química , Portadores de Fármacos , Durapatita/química , Óxido Ferrosoférrico/química , Microesferas , Materiales Biocompatibles/química , Imanes , Microscopía Electrónica de Rastreo , Nanoestructuras/química , Nanoestructuras/ultraestructura , Porosidad , Vancomicina/química , Difracción de Rayos XRESUMEN
BACKGROUND: single-stage transanal endorectal pull-through (TEPT) is a new technique for surgery of Hirschsprung's disease (HD). TEPT can be assisted by laparoscopy (laparoscopic assisted transanal pull-through, LATP) or with non-additional procedure (total transanal endorectal pull-through, TTEP). This study was undertaken to evaluate the long-term outcome of these approaches in children with HD. METHODS: we retrospectively studied 131 patients (112 males and 19 females) aged 7 days to 14 years who underwent single-stage TEPT from October 2003 to July 2008. The medical records were reviewed for pre-, intra- and immediate post-operative complications. The data on stool pattern and complications were collected during the follow-up. Outcome was measured by continence evaluation score. RESULTS: no patients had intraoperative complications, but 5 had minor immediate postoperative complications. Late postoperative complications in 12 patients included enterocolitis (4 patients, one with severe enterocolitis died 7 months after operation), soiling (6) and constipation (2). There was a significantly higher frequency of stool in patients aged more than 36 months and those with a resected colon more than 30 cm (P<0.05). LATP showed significantly higher frequency of stool and soiling (P<0.05). Of the 54 patients who were older than 3 years at the time of follow-up, continence score was normal in 10, good in 39, fair in 3, and poor in 2. Seventy-seven patients achieved good bowel control in 12.8 ± 8.11 months after operation, 93.5 5% of whom within 24 months. Stool function was not improved in patients more than 30 months old after operation. CONCLUSIONS: the long-term outcome of single stage TEPT was excellent. There were few postoperative complications, and stool pattern improved gradually to an excellent level within 24 months. Internal plication can be a good option for reducing the dilated proximal colon.