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Herpes Zóster , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Herpes Zóster/complicaciones , Herpes Zóster/patología , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/patología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/patología , Masculino , AncianoRESUMEN
OBJECTIVE: To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of antivascular endothelial growth factor (VEGF) agents. STUDY DESIGN: Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into 2 groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. RESULTS: A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84 ± 45 days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR 11.4, P = .008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR 13.8, P = .003), patent ductus arteriosus ligation (OR 10.7, P = .032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR 7.0, P = .018). CONCLUSIONS: All anti-VEGF agents carry a risk of ROP reactivation, with the risk being greater with ranibizumab 0.25 mg than with bevacizumab 0.625 mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.
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Inhibidores de la Angiogénesis , Bevacizumab , Inyecciones Intravítreas , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/tratamiento farmacológico , Inyecciones Intravítreas/efectos adversos , Masculino , Femenino , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Recién Nacido , Bevacizumab/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Factores de Riesgo , Ranibizumab/administración & dosificación , Ranibizumab/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Retrospectivos , Recurrencia , Recien Nacido Prematuro , LactanteRESUMEN
The scale of post-transcriptional regulation and the implications of its interplay with other forms of regulation in environmental acclimation are underexplored for organisms of the domain Archaea. Here, we have investigated the scale of post-transcriptional regulation in the extremely halophilic archaeon Halobacterium salinarum NRC-1 by integrating the transcriptome-wide locations of transcript processing sites (TPSs) and SmAP1 binding, the genome-wide locations of antisense RNAs (asRNAs), and the consequences of RNase_2099C knockout on the differential expression of all genes. This integrated analysis has discovered that 54% of all protein-coding genes in the genome of this haloarchaeon are likely targeted by multiple mechanisms for putative post-transcriptional processing and regulation, with about 20% of genes likely being regulated by combinatorial schemes involving SmAP1, asRNAs, and RNase_2099C. Comparative analysis of mRNA levels (transcriptome sequencing [RNA-Seq]) and protein levels (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry [SWATH-MS]) for 2,579 genes over four phases of batch culture growth in complex medium generated additional evidence for the conditional post-transcriptional regulation of 7% of all protein-coding genes. We demonstrate that post-transcriptional regulation may act to fine-tune specialized and rapid acclimation to stressful environments, e.g., as a switch to turn on gas vesicle biogenesis to promote vertical relocation under anoxic conditions and modulate the frequency of transposition by insertion sequence (IS) elements of the IS200/IS605, IS4, and ISH3 families. Findings from this study are provided as an atlas in a public Web resource (https://halodata.systemsbiology.net). IMPORTANCE While the transcriptional regulation landscape of archaea has been extensively investigated, we currently have limited knowledge about post-transcriptional regulation and its driving mechanisms in this domain of life. In this study, we collected and integrated omics data from multiple sources and technologies to infer post-transcriptionally regulated genes and the putative mechanisms modulating their expression at the protein level in Halobacterium salinarum NRC-1. The results suggest that post-transcriptional regulation may drive environmental acclimation by regulating hallmark biological processes. To foster discoveries by other research groups interested in the topic, we extended our integrated data to the public in the form of an interactive atlas (https://halodata.systemsbiology.net).
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Archaea , Transcriptoma , Humanos , Archaea/genética , Transcriptoma/genética , Genoma , ARN sin Sentido/genética , Ribonucleasas/genéticaRESUMEN
Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.
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Tacrolimus/agonistas , Factor de Impacto , Voriconazol/agonistas , Citocromo P-450 CYP2C19/análisis , Técnicas In Vitro/métodos , Preparaciones Farmacéuticas/administración & dosificación , Adaptación Psicológica/clasificaciónRESUMEN
Transcription Factor 4 (TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4. We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.
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Discapacidad Intelectual , Neuronas , Proliferación Celular/genética , Niño , Humanos , Hiperventilación/metabolismo , Discapacidad Intelectual/genética , Neuronas/metabolismo , Factor de Transcripción 4/genética , Factor de Transcripción 4/metabolismoRESUMEN
PURPOSE: The prolyl 3-hydroxylase family member 4 gene (P3H4) is involved in the development of human cancers. The association of P3H4 with bladder cancer (BC) prognosis is unclear. This study aimed to analyze the association of P3H4 with BC prognosis. METHODS: RNA-Seq data were downloaded from The Cancer Genome Atlas project and BC microarray datasets (GSE13507, GSE31684, and GSE32548) were downloaded from the Gene Expression Omnibus database. We analyzed the differences in P3H4 expression levels between BC tumors and non-tumor tissues and between samples with different clinical information. The association of P3H4 and P3H4-related genes with BC prognosis and the possibility of using P3H4 expression as a prognostic biomarker in BC patients were also analyzed. RevMan was used to perform the meta-analysis. RESULTS: P3H4 was upregulated in BC tissues compared with the adjacent non-tumor tissues (p = 4.06e-08). Univariate Cox regression analysis and meta-analysis showed that high P3H4 expression level contributed to a poor BC prognosis (Hazard ratio, HR = 1.348, 95% CI 1.140-1.594, p = 4.89e-04; meta-analysis: HR = 1.45, 95% CI 1.10-1.91; p = 9.00e-03). Among the genes related to P3H4, the PLOD1 gene was closely associated with P3H4 expression (r = 0.620, p = 2.49e-44). Also, a meta-analysis showed that PLOD1 expression was associated with a poor prognosis in BC patients (HR = 1.77, 95% CI 1.31-2.38; p = 2.00e-04). CONCLUSIONS: The P3H4 and PLOD1 genes might be used as reliable prognostic biomarkers for BC.
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Neoplasias de la Vejiga Urinaria , Autoantígenos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/genética , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/metabolismo , Pronóstico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Morphological characterization and fluid dynamics simulations were carried out to classify the rupture status of 71 (36 unruptured, 35 ruptured) patient specific cerebral aneurysms using a machine learning approach together with statistical techniques. Eleven morphological and six hemodynamic parameters were evaluated individually and collectively for significance as rupture status predictors. The performance of each parameter was inspected using hypothesis testing, accuracy, confusion matrix, and the area under the receiver operating characteristic curve. Overall, the size ratio exhibited the best performance, followed by the diastolic wall shear stress, and systolic wall shear stress. The prediction capability of all 17 parameters together was evaluated using eight different machine learning algorithms. The logistic regression achieved the highest accuracy (0.75), whereas the random forest had the highest area under curve value among all the classifiers (0.82), surpassing the performance exhibited by the size ratio. Hence, we propose the random forest model as a tool that can help improve the rupture status prediction of cerebral aneurysms.
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Aneurisma Roto , Aneurisma Intracraneal , Hemodinámica , Humanos , Hidrodinámica , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Quizalofop-p-ethyl (QPE), a unitary R configuration aromatic oxyphenoxypropionic acid ester (AOPP) herbicide, was widely used and had led to detrimental environmental effects. For finding the QPEdegrading bacteria and promoting the biodegradation of QPE, a series of studies were carried out. RESULTS: A QPE-degrading bacterial strain YC-XJ1 was isolated from desert soil and identified as Methylobacterium populi, which could degrade QPE with methanol by cometabolism. Ninety-seven percent of QPE (50 mg/L) could be degraded within 72 h under optimum biodegradation condition of 35°C and pH 8.0. The maximum degradation rate of QPE was 1.4 mg/L/h, and the strain YC-XJ1 exhibited some certain salinity tolerance. Two novel metabolites, 2-hydroxy-6-chloroquinoxaline and quinoxaline, were found by high-performance liquid chromatography/mass spectroscopy analysis. The metabolic pathway of QPE was predicted. The catalytic efficiency of strain YC-XJ1 toward different AOPPs herbicides in descending order was as follows: haloxyfop-pmethyl ≈ diclofop-methyl ≈ fluazifop-p-butyl N clodinafop-propargyl N cyhalofop-butyl N quizalofop-p-ethyl N fenoxaprop-p-ethyl N propaquizafop N quizalofop-p-tefuryl. The genome of strain YC-XJ1 was sequenced using a combination of PacBio RS II and Illumina platforms. According to the annotation result, one α/ß hydrolase gene was selected and named qpeh1, for which QPE-degrading function has obtained validation. Based on the phylogenetic analysis and multiple sequence alignment with other QPE-degrading esterases reported previously, the QPEH1 was clustered with esterase family V. CONCLUSION: M. populi YC-XJ1 could degrade QPE with a novel pathway, and the qpeh1 gene was identified as one of QPE-degrading esterase gene.
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Propionatos/metabolismo , Quinoxalinas/metabolismo , Methylobacterium/metabolismo , Microbiología del Suelo , Biodegradación Ambiental , Methylobacterium/enzimología , Methylobacterium/genética , Análisis de Secuencia de Proteína , Esterasas/análisis , Esterasas/metabolismo , Herbicidas , Hidrolasas/análisis , Hidrolasas/metabolismo , HidrólisisRESUMEN
SUMMARY OBJECTIVE Lung cancer is the leading cause of cancer-related death. To reduce lung cancer mortality and detect lung cancer in early stages, low dose CT screening is required. A meta-analysis was conducted to verify whether screening could reduce lung cancer mortality and to determine the optimal screening program. METHODS We searched PubMed, Web of Science, Cochrane library, ScienceDirect, and relevant Chinese databases. Randomized controlled trial studies with participants that were smokers older than 49 years (smoking >15 years or quit smoking 10 or 15 years ago) were included. RESULTS Nine RCT studies met the criteria. LDCT screening could find more lung cancer cases (RR=1.58, 95%CI=1.25-1.99, P<0.001) and more stage I lung cancers (RR=3.45, 95%CI=2.08-5.72, P<0.001) compared to chest-X ray or the no screening group. This indicated a statistically significant reduction in lung-cancer-specific mortality (RR=0.84, 95%CI=0.75-0.95, P=0.004), but without a statistically reduction in mortality due to all causes (RR=1.26, 95%CI=0.89-1.78, P=0.193). Annually, LDCT screening was sensitive in finding more lung cancers. CONCLUSIONS Low-dose CT screening is effective in finding more lung cancer cases and decreasing the deaths from lung cancer. Annual low-dose CT screening may be better than a biennial screening to detect more early-stage lung cancer cases.
RESUMO OBJETIVO O câncer de pulmão é a principal causa de mortes relacionadas ao câncer. Para reduzir a mortalidade por câncer de pulmão e encontrar câncer de pulmão em um estágio inicial, é necessária uma triagem por tomografia de baixa dose. Uma meta-análise foi emitida para testemunhar se a triagem poderia reduzir a mortalidade por câncer de pulmão e investigar o melhor programa de triagem. MÉTODOS Pesquisamos PubMed, Web of Science, biblioteca Cochrane, ScienceDirect e relevante banco de dados chinês. Ensaios clínicos controlados aleatórios, em que os participantes eram fumantes com mais de 49 anos (tabagismo >15 anos ou parar de fumar 10 ou 15 anos atrás) foram incluídos. RESULTADOS Nove estudos RCT preencheram os critérios. O rastreamento de LDCT pôde encontrar mais cânceres de pulmão (RR=1,58, IC 95%=1,25-1,99, P<0,001) e mais cânceres de estágio I do pulmão (RR=3,45, IC 95%=2,08-5,72, P<0,001) em comparação com raio X do tórax ou nenhum grupo de triagem. Ele indicou uma redução estatisticamente significativa na mortalidade específica do câncer de pulmão (RR=0,84, IC 95%=0,75-0,95, P=0,004), mas sem uma redução estatisticamente significativa na mortalidade por todas as causas (RR=1,26, IC 95%=0,89-1,78, P=0,193). Anualmente, o rastreamento de LDCT foi sensível em encontrar mais cânceres de pulmão. CONCLUSÕES A triagem de TC de baixa dose é eficaz para encontrar mais cânceres de pulmão e diminuir as mortes por câncer de pulmão. Para encontrar mais cânceres de pulmão em estágio inicial, a triagem anual de tomografia de baixa dose pode ser melhor do que a triagem bianual.
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Humanos , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/diagnóstico por imagen , Tamizaje Masivo , Factores de Riesgo , Detección Precoz del CáncerRESUMEN
To investigate the mechanism of different exercise patterns on neurological function after focal cerebral ischaemia in rats. Rats with focal cerebral cerebral ischaemia were randomly divided into an aerobic exercise group, an exhaustive exercise group and a control group, with 8 rats in each group. A score for nerve function in each group was calculated, and the ultrastructure of nerve cells was observed. Levels of NO and NOS in the brain motor area of the âârats were measured in each group. The aerobic exercise group had lower nerve function scores than the exhaustive exercise group and higher scores than the control group (P<0.05). Under transmission electron microscopy, irregular shapes and organs were observed in nerve cells in the control group, while regular cell shapes and organs were observed in the aerobic exercise group. The aerobic exercise group and exhaustive exercise group had higher measures of NO content, NOS activity and eNOS, nNOS and iNOS gene expression than the control group, but eNOS expression in the aerobic exercise group and iNOS expression in the exhaustive exercise group were clearly higher according to RT-PCR (P<0.05). Aerobic exercise can promote the expression of NOS, mainly in eNOS, which can promote nerve repair.
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Isquemia Encefálica/fisiopatología , Regeneración Nerviosa/fisiología , Óxido Nítrico/fisiología , Condicionamiento Físico Animal/métodos , Animales , Isquemia Encefálica/terapia , Modelos Animales de Enfermedad , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas Sprague-DawleyRESUMEN
Here, we report the identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge, Guyana. In March 2019, 14 employees of Chongqing Bosai Mining Company, China, working in a manganese mining of Guyana, had unexplained fever, and two of them died. We obtained lung and brain tissues as well as the blood samples from the two deceased cases (patient No. 1 and 2), and bronchoscopy lavages and cerebrospinal fluid samples from one severe case (patient No. 3), respectively. All samples were tested by pathological examination, high-throughput sequencing, and real-time PCR. Pathological detection showed the presence of spore-like structures in the lung tissue of patient No. 1, indicating a fungal infection in this patient. Nanopore sequencing identified the existing of H. capsulatum in the lung tissue sample within 13 h. Next-generation sequencing identified specific fragments of H. capsulatum in all of the samples tested (lung, brain and blood serum from the deceased cases, and plasma from the severe case). Real-time PCR assays did not reveal any viral infection related to transmission from bat feces. We conclude that H. capsulatum was the causative pathogen of this disease cluster based on epidemiologic, clinical, pathological and nucleic acid evidence.
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OBJECTIVE: Lung cancer is the leading cause of cancer-related death. To reduce lung cancer mortality and detect lung cancer in early stages, low dose CT screening is required. A meta-analysis was conducted to verify whether screening could reduce lung cancer mortality and to determine the optimal screening program. METHODS: We searched PubMed, Web of Science, Cochrane library, ScienceDirect, and relevant Chinese databases. Randomized controlled trial studies with participants that were smokers older than 49 years (smoking >15 years or quit smoking 10 or 15 years ago) were included. RESULTS: Nine RCT studies met the criteria. LDCT screening could find more lung cancer cases (RR=1.58, 95%CI=1.25-1.99, P<0.001) and more stage I lung cancers (RR=3.45, 95%CI=2.08-5.72, P<0.001) compared to chest-X ray or the no screening group. This indicated a statistically significant reduction in lung-cancer-specific mortality (RR=0.84, 95%CI=0.75-0.95, P=0.004), but without a statistically reduction in mortality due to all causes (RR=1.26, 95%CI=0.89-1.78, P=0.193). Annually, LDCT screening was sensitive in finding more lung cancers. CONCLUSIONS: Low-dose CT screening is effective in finding more lung cancer cases and decreasing the deaths from lung cancer. Annual low-dose CT screening may be better than a biennial screening to detect more early-stage lung cancer cases.
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Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Tomografía Computarizada por Rayos X/métodos , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Tamizaje Masivo , Factores de RiesgoRESUMEN
PURPOSE: To investigate the protective effects of Polygonatum sibiricum polysaccharide (PSP) on acute heart failure (AHF) in rats. METHODS: Sixty rats were randomly divided into control, model, and low-, middle- and high-dose PSP groups, 12 rats in each group. The low-, medium- and high-dose PSP groups were intragastrically administrated with 100, 200 and 400 mg/kg PSP for 5 days, respectively. On the sixth day, the AHF model was established by intraperitoneal injection of adriamycin. After 24h, the cardiac function, serum biochemical indexes, myocardial ATPase and succinate dehydrogenase levels and apoptosis related protein expressions were determined. RESULTS: Compared with model group, in high-dose PSP group the heart rate, left ventricular systolic pressure, ±dp/dtmax, serum superoxide dismutase level, myocardial Na+-K+-ATPase, Ca2+-Mg2+-ATPase and succinate dehydrogenase levels and myocardial Bcl-2 and Caspase-3 protein expression levels were significantly increased (P<0.05), the left ventricular end diastolic pressure, serum cTnI, CK-MB, TNF-α, IL-6, malondialdehyde and nitric oxide levels and myocardial Bax and cleaved Caspase-3 protein expression levels were significantly decreased (P<0.05). CONCLUSIONS: Polysaccharide can prevent the acute heart failure induced by adriamycin. The mechanism may be related to its anti-oxidative stress, anti-inflammation and inhibition of cardiac myocyte apoptosis.
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Doxorrubicina/farmacología , Insuficiencia Cardíaca/prevención & control , Polygonatum/química , Polisacáridos/uso terapéutico , Enfermedad Aguda , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Purpose: To investigate the protective effects of Polygonatum sibiricum polysaccharide (PSP) on acute heart failure (AHF) in rats. Methods: Sixty rats were randomly divided into control, model, and low-, middle- and high-dose PSP groups, 12 rats in each group. The low-, medium- and high-dose PSP groups were intragastrically administrated with 100, 200 and 400 mg/kg PSP for 5 days, respectively. On the sixth day, the AHF model was established by intraperitoneal injection of adriamycin. After 24h, the cardiac function, serum biochemical indexes, myocardial ATPase and succinate dehydrogenase levels and apoptosis related protein expressions were determined. Results: Compared with model group, in high-dose PSP group the heart rate, left ventricular systolic pressure, ±dp/dtmax, serum superoxide dismutase level, myocardial Na+-K+-ATPase, Ca2+-Mg2+-ATPase and succinate dehydrogenase levels and myocardial Bcl-2 and Caspase-3 protein expression levels were significantly increased (P 0.05), the left ventricular end diastolic pressure, serum cTnI, CK-MB, TNF-, IL-6, malondialdehyde and nitric oxide levels and myocardial Bax and cleaved Caspase-3 protein expression levels were significantly decreased (P 0.05). Conclusions: Polysaccharide can prevent the acute heart failure induced by adriamycin. The mechanism may be related to its anti-oxidative stress, anti-inflammation and inhibition of cardiac myocyte apoptosis.(AU)
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Animales , Ratas , Insuficiencia Cardíaca/veterinaria , Polisacáridos , Sustancias Protectoras/análisis , Polygonatum , Estrés Oxidativo , Apoptosis , Modelos AnimalesRESUMEN
Abstract Purpose: To investigate the protective effects of Polygonatum sibiricum polysaccharide (PSP) on acute heart failure (AHF) in rats. Methods: Sixty rats were randomly divided into control, model, and low-, middle- and high-dose PSP groups, 12 rats in each group. The low-, medium- and high-dose PSP groups were intragastrically administrated with 100, 200 and 400 mg/kg PSP for 5 days, respectively. On the sixth day, the AHF model was established by intraperitoneal injection of adriamycin. After 24h, the cardiac function, serum biochemical indexes, myocardial ATPase and succinate dehydrogenase levels and apoptosis related protein expressions were determined. Results: Compared with model group, in high-dose PSP group the heart rate, left ventricular systolic pressure, ±dp/dtmax, serum superoxide dismutase level, myocardial Na+-K+-ATPase, Ca2+-Mg2+-ATPase and succinate dehydrogenase levels and myocardial Bcl-2 and Caspase-3 protein expression levels were significantly increased (P<0.05), the left ventricular end diastolic pressure, serum cTnI, CK-MB, TNF-α, IL-6, malondialdehyde and nitric oxide levels and myocardial Bax and cleaved Caspase-3 protein expression levels were significantly decreased (P<0.05). Conclusions: Polysaccharide can prevent the acute heart failure induced by adriamycin. The mechanism may be related to its anti-oxidative stress, anti-inflammation and inhibition of cardiac myocyte apoptosis.
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Animales , Masculino , Ratas , Polisacáridos/uso terapéutico , Doxorrubicina/farmacología , Polygonatum/química , Insuficiencia Cardíaca/prevención & control , Enfermedad Aguda , Ratas Sprague-Dawley , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad , Proteína X Asociada a bcl-2/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.
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Carcinoma de Células Escamosas/genética , Biología Computacional/métodos , Neoplasias Esofágicas/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Área Bajo la Curva , Carcinoma de Células Escamosas de Esófago , HumanosRESUMEN
Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.
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Humanos , Carcinoma de Células Escamosas/genética , Biología Computacional/métodos , Neoplasias Esofágicas/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Área Bajo la CurvaRESUMEN
BACKGROUND: The clinical significance of pericentric inversion of chromosome 9 [inv (9)] remains unclear. METHODS: This case control study assessed girls with short stature. According to karyotypes, the subjects were divided into inv (9) [46,XX,inv (9)(p12q13) and 46,XX,inv (9)(p11q13)], Turner syndrome (45, X) and control (normal 46, XX) groups, respectively. Detailed clinical features were compared. RESULTS: Height standard deviation score (SDS) values at diagnosis were -2.51±0.58, -3.71±2.12 and -2.5±1.24 for inv (9), (45, X) and control groups, respectively (p=0.022). The inv (9) group showed lower body mass index (BMI) values compared with the (45, X) and control groups (F=5.097, p=0.008). Similar growth hormone deficiency (GHD) incidences were found in all groups. Interestingly, height SDS was positively correlated with mother height and patient BMI SDS (r=0.51, p=0.036; r=0.576, p=0.023, respectively) in the inv (9) group. In the (45, X) group, height SDS was positively correlated with birth weight (r=0.392, p=0.039). CONCLUSIONS: Short stature in inv (9) girls was correlated with low birth weight (LBW) and mother height.
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Estatura/genética , Inversión Cromosómica/genética , Enanismo Hipofisario/patología , Trastornos del Crecimiento/patología , Hormona de Crecimiento Humana/deficiencia , Síndrome de Turner/patología , Estudios de Casos y Controles , Niño , Análisis Citogenético , Enanismo Hipofisario/genética , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/genética , Humanos , Síndrome de Turner/genéticaRESUMEN
Abstract The aim of this paper is to identify and investigate an endophytic fungus (strain 28) that was isolated from Houttuynia cordata Thunb, a famous and widely-used Traditional Chinese Medicine. Based on morphological methods and a phylogenetic analysis of ITS sequences, this strain was identified as Chaetomium globosum. An antifungal activity bioassay demonstrated that the crude ethyl acetate (EtOAc) extracts of strain 28 had a wide antifungal spectrum and strong antimicrobial activity, particularly against Exserohilum turcicum (Pass.) Leonard et Suggs, Botrytis cinerea persoon and Botrytis cinerea Pers. ex Fr. Furthermore, the fermentation conditions, extraction method and the heat stability of antifungal substances from strain 28 were also studied. The results showed that optimal antifungal activity can be obtained with the following parameters: using potato dextrose broth (PDB) as the base culture medium, fermentation for 4–8 d (initial pH: 7.5), followed by extraction with EtOAc. The extract was stable at temperatures up to 80 °C. This is the first report on the isolation of endophytic C. globosum from H. cordata to identify potential alternative biocontrol agents that could provide new opportunities for practical applications involving H. cordata.