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1.
Environ Pollut ; 273: 116467, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33453699

RESUMEN

As zoned areas of industries, industrial parks have great impacts on the environment. Several studies have demonstrated that chemical compounds and heavy metals released from industrial parks can contaminate soil, water, and air. However, as an emerging pollutant, antimicrobial resistance genes (ARGs) in industrial parks have not yet been investigated. Here, we collected soil samples from 35 sites in an industrial park in China and applied a metagenomics strategy to profile the ARGs and virulence factors (VFs). We further compared the relative abundance of ARGs between the sites (TZ_31-35) located in a beta-lactam antimicrobial-producing factory and other sites (TZ_1-30) in this industrial park. Metagenomic sequencing and assembly generated 14, 383, 065 contigs and 17, 631, 051 open reading frames (ORFs). Taxonomy annotation revealed Proteobacteria and Actinobacteria as the most abundant phylum and class, respectively. The 32 pathogenic bacterial genera listed in the virulence factor database (VFDB) were all identified from the soil metagenomes in this industrial park. In total, 685,354 ARGs (3.89% of the ORFs) and 272,694 virulence factors (VFs) (1.55% of the ORFs) were annotated. These ARGs exhibited resistance to several critically important antimicrobials, such as rifampins, fluroquinolones, and beta-lactams. In addition, no significant difference in the relative abundance of ARGs was observed between sites TZ_31-35 and TZ_1-30, indicating that ARGs have already disseminated widely in this industrial park. The present study gave us a better understanding of the whole picture of the resistome and virulome in the soil of the industrial park and suggested that we should treat the industrial park as a whole in the surveillance and maintenance of ARGs.

2.
Chin Med ; 15: 60, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32518585

RESUMEN

Background: Anthraquinone glycosides extracted from rhubarb have been proven to have significant therapeutic effects on ischaemic stroke. It is well known that anthraquinone glycosides are not easily absorb. Thus, how can rhubarb anthraquinone glycosides (RAGs) exert protective effects on the brain? Is this protective effect related to interactions between RAGs and intestinal flora? Methods: The model used in this study was established by middle cerebral artery occlusion (MCAO) and reperfusion. Twenty-seven adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups: the normal group (A) (non-MCAO + 0.5% sodium carboxymethyl cellulose (CMC-Na)), model group (B) (MCAO + 0.5% CMC-Na) and medicine group (C) (MCAO + RAGs (15 mg/(kg day)). The rats were fed by gavage once a day for 7 days. Fresh faeces were collected from the normal group to prepare the intestinal flora incubation liquid. Add RAGs, detect the RAGs and the corresponding anthraquinone aglycones by HPLC-UV at different time points. On the 8th day, the rats were euthanized, and the colonic contents were collected and analysed by high-throughput sequencing. In addition, 12 adult male SD rats were randomly divided into 2 groups: the normal group (D) (non-MCAO + RAGs (15 mg/(kg day)) and model group (E) (MCAO + RAGs (15 mg/(kg day)). The rats were fed by gavage immediately after reperfusion. Blood was collected from the orbital venous plexus, and the RAGs and anthraquinone aglycones were detected by HPLC-UV. Results: The abundance and diversity of the intestinal flora in rats decreased after cerebral ischaemia-reperfusion injury (CIRI). RAGs could effectively improve the abundance of the intestinal flora. In addition, in vitro metabolism studies showed that RAGs were converted into anthraquinone aglycones by intestinal flora. In the in vivo metabolism studies, RAGs could not be detected in the plasma; in contrast, the corresponding anthraquinone aglycones could be detected. Absorption of RAGs may be inhibited in rats with CIRI. Conclusions: CIRI may lead to intestinal flora disorder in rats, and after the administration of RAGs, the abundance of intestinal flora can be improved. RAGs can be metabolized into their corresponding anthraquinone aglycones by intestinal flora so that they can be absorbed into the blood.

3.
J Stroke Cerebrovasc Dis ; 29(7): 104823, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32362555

RESUMEN

BACKGROUND: Lesions in multiple arterial territories is one of the typical features of malignancy patients with cryptogenic stroke. Hence, if patients with cryptogenic stroke display such feature, occult cancer could be predicted. The study aimed to analyze the predictive ability of the number of territories involved on DWI-MRI for occult systemic malignancy (OSM) in patients with cryptogenic stroke. METHODS: We enrolled patients with cryptogenic stroke without a diagnosis of malignancy at stroke onset between January 2013 and November 2018. Clinical variables were analyzed between cryptogenic stroke patients with and without OSM through univariate and multiple logistic regression analyses. Points for OSM were generated by ß-coefficients. The sensitivity and specificity of the risk score were assessed by the area under the receiver operating characteristic curve (AUROC). The cutoff value for predicting OSM was determined by the maximum Youden index. RESULTS: Among 108 cyptogenic stroke patients, compared to patients without OSM (n = 96), patients with OSM (n = 12) had a lower nutrition status (P = 0.031), higher plasma D-dimer levels (P < 0.001) and more territories involved on DWI-MRI (P < 0.001). Multiple logistic regression analysis revealed that plasma D-dimer levels (OR, 3.54; 95% Cl, 1.62-7.76; P = 0.002) and the number of territories involved (OR, 4.45; 95% CI, 1.25-15.80; P = 0.021) independently predicted OSM. The predictive score system built upon the number of territories showed good discrimination with an AUROC of 0.84 (95% CI, 0.71-0.96). The cutoff value was 2 with a maximum Youden's index of 0.56, which means that patients with more than one territory involved on DWI-MRI may need extensive screening for OSM. CONCLUSIONS: The number of territories involved on DWI-MRI was a valid predictor for OSM in cryptogenic stroke patients who need to undergo further evaluations .


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Neoplasias/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Coagulación Sanguínea , Bases de Datos Factuales , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/diagnóstico , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Trombofilia/sangre , Trombofilia/diagnóstico , Trombofilia/etiología
4.
Infect Drug Resist ; 13: 851-854, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32214831

RESUMEN

Abstract: The emergence of the plasmid-borne colistin-resistant gene (mcr-1) poses a great threat to human health. What is worse, the recent observations of the co-existence of mcr-1 with other antimicrobial resistance genes in some bacteria cause further concern. Here, we present the first report of a wild Escherichia coli strain that co-carries an mcr-1 encoding phage-like IncY plasmid (pR15_MCR-1) and a bla NDM-5 encoding IncX3 plasmid (pR15_NDM-5) from a pharmaceutical industry, wastewater treatment plant, in China. This study highlights the spreading of E. coli carrying both mcr-1 and bla NDM-5 genes in the pharmaceutical industry. Importance: Escherichia coli strains that carry both mcr-1 and bla NDM-5 genes are of great health concern and are already found in humans and animals worldwide, yet there is a paucity of observations of this resistant strain in the environment. Here we present the first isolation of an E. coli strain (R15) that co-carries mcr-1 and bla NDM-5 genes from a wastewater treatment plant in China. Whole-genome sequencing indicated that R15 harbored two plasmids, pR15_MCR-1 and pR15_NDM-5, that carry mcr-1 and bla NDM-5, respectively. The observation of this wild-derived E. coli strain that carries mcr-1 and bla NDM-5 genes simultaneously calls for the urgency to improve monitoring and reducing its further spreading.

5.
Front Pharmacol ; 11: 150, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32180719

RESUMEN

Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. We have previously reported that compound fuling granule (CFG), a traditional Chinese medicinal preparation used to treat ovarian cancer in China for over 20 years, significantly promotes cell cycle arrest, apoptosis, senescence, TGFß-induced invasion and migration, tumor growth, and distant metastasis in ovarian cancer cells. However, the underlying mechanisms are not clear. In the present study, we found that PHF19 expression in ovarian cancer cells positively correlated with their resistance ability to CFG. In addition, PHF19 overexpression increased the resistance of HEY-T30 and SKOV3 cells to CFG, while knockdown of PHF19 enhanced their sensitivity to CFG. Moreover, CFG significantly inhibited the expression of PHF19 both in mRNA and protein levels in these cells. Gain of function and loss of function experiments further proved that PHF19 is a crucial mediator involved in the ovarian cancer progression, including cell proliferation, invasion, migration, and stemness. Importantly, rescue the expression of PHF19 reverted CFG-induced suppression in ovarian cancer cell growth, EMT and stemness, while PHF19 knockdown accelerated CFG's anti-tumor effect. Overall, our results provide a series of evidence to reveal that PHF19 is critical suppressor for CFG's anti-tumor effect in ovarian cancer.

6.
Biochem Biophys Res Commun ; 523(4): 887-893, 2020 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-31955887

RESUMEN

pH-sensitive polyethylene glycol-conjugated urokinase nanogels (PEG-UK) is a new form of urokinase (UK) nanogels that could release UK at certain pH values. In our former study, we demonstrated that the pH value in the infarcted brain significantly declined to the level that could trigger the delivery of UK from PEG-UK. Thrombolysis is recommended as the first choice for ischemic stroke within the time window. However, it is common for the patients to miss the thrombolysis time window, which is one of the major causes of bad prognosis from ischemic stroke. It remains promising for seeking therapeutic approaches for ischemic stroke by investigating potential protective reagents delivered out of the usually thrombolysis time window. In this study, the protective effect of administration of PEG-UK outside the usual time window and the underlying mechanisms were investigated. PEG-UK was administrated 2 h and a half after ischemic stroke Delayed administration of PEG-UK significantly ameliorated the severity of neurological deficits of permanent middle cerebral occlusion (pMCAO) rats and reduced the infiltration of inflammatory cells and the concentration of interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the brain tissues. The content of water and the leakage of Evans Blue (EB) in the PEG-UK group were also decreased. Maintenance of the expression of platelet-derived growth factor-C (PDGF-C) and inhibition of the upregulation of metalloproteinase proteins, low-density lipoprotein receptor-related protein (LRP), nuclear factor κB (NF-κB) p65 and cyclooxygenase-2 (Cox-2) were observed through western blotting and realtime PCR in the PEG-UK group. Besides, delayed administration of PEG-UK attenuated the up regulation of Caspase8 and Caspase9 and the cleavage of Caspase3 and poly (ADP-ribose) polymerase 1 (PARP1) in ischemic lesion sites. Moreover, PEG-UK treatment also inhibited the upregulation and phosphorylation of N-methyl-D-aspartic acid receptors (NMDARs), which has been revealed to play a vital role in mediating excito-neurotoxicity in ischemic stroke. In conclusion, through the inhibition of LRP/NF-κB/Cox-2 pathway, the Caspase cascade and activation of NMDARs, administration of PEG-UK outside the usual time window could still exert protective effects in pMCAO rats through the maintenance of the integrity of BBB and the inhibition of apoptosis and excito-neurotoxicity.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Nanogeles/química , Fármacos Neuroprotectores/uso terapéutico , Polietilenglicoles/química , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/complicaciones , Caspasas/metabolismo , Ciclooxigenasa 2/metabolismo , Activación Enzimática/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Infarto de la Arteria Cerebral Media/patología , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , FN-kappa B/metabolismo , Fármacos Neuroprotectores/farmacología , Neurotoxinas/toxicidad , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal/efectos de los fármacos , Accidente Cerebrovascular/complicaciones , Factores de Tiempo , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Activador de Plasminógeno de Tipo Uroquinasa/farmacología
7.
BMC Plant Biol ; 19(1): 572, 2019 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-31856725

RESUMEN

BACKGROUND: During tomato cultivation, tomato leaf mould is a common disease caused by Cladosporium fulvum (C. fulvum). By encoding Cf proteins, which can recognize corresponding AVR proteins produced by C. fulvum, Cf genes provide resistance to C. fulvum, and the resistance response patterns mediated by different Cf genes are not identical. Plants carrying the Cf-19 gene show effective resistance to C. fulvum in the field and can be used as new resistant materials in breeding. In this study, to identify key regulatory genes related to resistance and to understand the resistance response process in tomato plants carrying Cf-19, RNA sequencing (RNA-seq) was used to analyse the differences between the response of resistant plants (CGN18423, carrying the Cf-19 gene) and susceptible plants (Moneymaker (MM), carrying the Cf-0 gene) at 0, 7 and 20 days after inoculation (dai). RESULTS: A total of 418 differentially expressed genes (DEGs) were identified specifically in the CGN18423 response process. Gene Ontology (GO) analysis revealed that GO terms including "plasma membrane (GO_Component)", "histidine decarboxylase activity (GO_Function)", and "carboxylic acid metabolic process (GO_Process)", as well as other 10 GO terms, were significantly enriched. The "plant hormone signal transduction" pathway, which was unique to CGN18423 in the 0-7 dai comparison, was identified. Moreover, ten key regulatory points were screened from the "plant hormone signal transduction" pathway and the "plant pathogen interaction" pathway. Hormone content measurements revealed that the salicylic acid (SA) contents increased and peaked at 7 dai, after which the contents deceased and reached minimum values in both CGN18423 and MM plants at 20 dai. The jasmonic acid (JA) content increased to a very high level at 7 dai but then decreased to nearly the initial level at 20 dai in CGN18423, while it continued to increase slightly during the whole process from 0 to 20 dai in MM. CONCLUSIONS: The initial responses are very different between the resistant and susceptible plants. The "plant hormone signal transduction" pathway is important for the formation of Cf-19-mediated immunity. In addition, both JA and SA play roles in regulating the Cf-19-dependent resistance response.


Asunto(s)
Cladosporium/fisiología , Lycopersicon esculentum/genética , Enfermedades de las Plantas/genética , Inmunidad de la Planta/genética , Proteínas de Plantas/genética , Resistencia a la Enfermedad/inmunología , Ontología de Genes , Lycopersicon esculentum/inmunología , Lycopersicon esculentum/microbiología , RNA-Seq
8.
Medicine (Baltimore) ; 98(44): e17643, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689774

RESUMEN

BACKGROUND: Current research has proved that psoriasis is associated with serum uric acid (SUAC) levels. Our purpose is to clarify SUAC levels and the incidence of hyperuricemia in psoriasis patients, and to compare SUCA levels in different groups' psoriasis patients. METHODS: We plan to search 7 electronic bibliographic databases (PubMed, Embase, Cochrane, and 4 Chinese databases) from inception to August 2019. Literatures selection and data collection will be performed independently by 2 authors. The Newcastle-Ottawa scale will be used to assess the methodologic quality and bias of included studies. Firstly, standard pairwise meta-analysis will be used to examine the considered data synthesis. Secondly, if the identified studies appear sufficiently similar within and across the different comparisons between different groups of psoriasis patients, we will estimate SUAC levels using network meta-analysis in different age and ethnicity psoriasis patients. Mean difference, risk ratio, and 95% confidence intervals will be used to assess the SUAC levels and the incidence of hyperuricemia in psoriasis patients. The software of Stata and WinBUGS will be used to calculations. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: Our study will compare SUCA levels in different groups' psoriasis patients through network meta-analysis, and we believe our job is very meaningful. ETHICS AND DISSEMINATION: Our study is a secondary study of the existing literature. So, ethical and dissemination approval is not required.


Asunto(s)
Hiperuricemia/epidemiología , Psoriasis/epidemiología , Ácido Úrico/sangre , Factores de Edad , Grupos Étnicos , Humanos , Hiperuricemia/sangre , Incidencia , Metaanálisis en Red , Estudios Observacionales como Asunto , Psoriasis/sangre , Proyectos de Investigación , Características de la Residencia , Factores Sexuales
9.
Infect Drug Resist ; 12: 2775-2779, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31564927

RESUMEN

A multidrug-resistant Citrobacter freundii strain R17 was isolated from a wastewater treatment plant in China. Whole-genome sequencing of strain R17 revealed a new sequence type (ST412) chromosome (length 5,124,258 bp) and an Inc FII (Yp) group plasmid pCFR17_1 (length 206,820 bp). A total of 13 antibiotic-resistance genes (ARGs) that confer resistance to eight different antibiotic groups were encoded by strain R17 and 12 of them were carried by plasmid pCFR17_1. These data and analysis suggest that the environment-derived C. freundii strains may serve as potential sources of ARGs and highlight the need of further surveillance of this bacteria in the future.

10.
Front Microbiol ; 10: 1797, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31428078

RESUMEN

Background and Objectives: Wastewater treatment plants (WWTPs) are one of the major reservoirs for antimicrobial resistant bacteria (ARB) and antimicrobial resistance genes (ARGs) in the environment. Thus, the investigation on ARB and ARGs from WWTPs has attracted increasing attention in recent years. In order to uncover the resistome in a WWTP treating effluents from a pharmaceutical industry in China, the extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains were isolated and their whole genome sequences were obtained and analyzed. Moreover, metagenomic sequencing was applied to give a comprehensive view of antibiotic resistance in this WWTP. Methods: 18 ESBL-producing E. coli strains were isolated from a WWTP located in Taizhou, China on April, 2017. All strains were sequenced using Illumina HiSeq 2000 sequencer. The whole genome sequences were assembled using SPAdes software and annotated with RAST server. Sequence types (STs), plasmids, ARGs and virulence genes were predicted from the genomes using MLST, Plasmid Finder, ResFinder and Virulence Finder, respectively. Metagenomic DNA of the same sample was extracted and sequenced using Illumina Hiseq X Ten platform. Metagenomic sequences were assembled using SOAPdenovo software. Results: All 18 ESBL-producing E. coli strains were resistant to ampicillin, cefazolin, and ceftriaxone. Analysis of their genomes revealed that all strains carried beta-lactamase encoding genes and the most prevalent type was bla CTX-M . Various virulence genes and ARGs confronting resistance to other types of antimicrobial agents were also predicted. Further investigation on the metagenomics data indicated 11 ARGs with high amino acid identities to the known ARGs. Five of these ARGs, aadA1, aac(6')-lb-cr, flo(R), sul2 and sul1, were also present in the genomes of the ESBL-producing E. coli isolated from the same sample. Conclusion: Our study revealed the resistome of a pharmaceutical WWTP by both culture-dependent and metegenomic methods. The existence of ESBL-producing E. coli strains, indicating that pharmaceutical WWTP can play a significant role in the emergence of ARB. The occurrence of ARGs annotated from the metagenomic data suggests that pharmaceutical WWTP can play a significant role in the emergence of ARGs. Our findings highlight the need for strengthening the active surveillance of ARB and ARGs from pharmaceutical industry.

11.
Clin Lab ; 65(7)2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31307180

RESUMEN

BACKGROUND: An updated meta-analysis was performed to clarify the effects of TGF-ß1 T869C polymorphism on the risk of diabetic nephropathy (DN) in the Chinese population. METHODS: The studies were searched using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Ser-vice Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up to October 2018. RESULTS: A total of 8 studies including 1,075 DN cases, 610 healthy controls, and 901 diabetes mellitus (DM) con-trols were involved in this meta-analysis. Overall, a significantly decreased risk of DN was associated with all vari-ants of TGF-ß1 T869C when compared with the healthy group (T vs. C, OR = 0.71, 95% CI = 0.61 - 0.83; TT vs. CC, OR = 0.51, 95% CI = 0.37 - 0.69; TT + CT vs. CC, OR = 0.64, 95% CI = 0.51 - 0.82; TT vs. CC + CT, OR = 0.62, 95% CI = 0.48 - 0.82) or DM (T vs. C, OR = 0.65, 95% CI = 0.56 - 0.76; TT vs. CC, OR = 0.31, 95% CI = 0.17 - 0.55; TT + CT vs. CC, OR = 0.67, 95% CI = 0.54 - 0.84; TT vs. CC + CT, OR = 0.27, 95% CI = 0.13 - 0.55), as well as their combinations (T vs. C, OR = 0.67, 95% CI = 0.60 - 0.76; TT vs. CC, OR = 0.34, 95% CI = 0.21 - 0.56; TT + CT vs. CC, OR = 0.67, 95% CI = 0.56 - 0.80; TT vs. CC + CT, OR = 0.32, 95% CI = 0.17 - 0.57). The sub-group analyses stratified by geographic areas revealed significant results in South China. CONCLUSIONS: This meta-analysis showed that the TGF-ß1 T869C variants may influence DN risk in Chinese, and further studies with gene-gene and gene-environment interactions are required to confirm this conclusion.


Asunto(s)
Nefropatías Diabéticas/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Factor de Crecimiento Transformador beta1/genética , Grupo de Ascendencia Continental Asiática/genética , China , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Genotipo , Humanos , Oportunidad Relativa
12.
Sci Data ; 5: 180222, 2018 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-30398469

RESUMEN

Because of poor differentiation among the members of genus Comamonas using phenotypic methods, human infections caused by C. kerstersii are sporadically reported in the literature. Here, we represent the first complete genome sequence of C. kerstersii 8943, which caused peritonitis in a patient with continuous ambulatory peritoneal dialysis (CAPD). The complete genome with no gaps was obtained using third-generation Pacific Biosciences (PacBio) RSII sequencing system with single-molecule real-time (SMRT) analysis. Protein-coding genes, rRNAs and tRNAs were predicted. Functional annotations of the genome using different databases revealed several genes related to pathogenicity including antibiotic resistance genes and prophages. Our work demonstrates that whole genome sequencing can enhance the resolution of clinical investigations and our data can be used as a reference genome during the rapid diagnosis of C. kerstersii infections in the future.


Asunto(s)
Comamonas/genética , Genoma Bacteriano , Peritonitis/microbiología , Humanos , Análisis de Secuencia de ADN , Secuenciación Completa del Genoma
13.
J Cancer ; 9(18): 3382-3393, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30271500

RESUMEN

Our previous studies have demonstrated that the compound fuling granule (CFG), a traditional Chinese medicine, suppresses ovarian cancer cell growth, migration and metastasis. However, the underlying mechanisms remain to be fully elucidated. In this study, we found that CFG could induce mitochondrial fragmentation, mitochondrial membrane potential reduction and cytochrome c release in ovarian SKOV3 cancer cells. In addition, both metabolomics and transcriptomics approaches were applied to illustrate the systemic mechanism of CFG on ovarian cancer formation and progression. To this end, we established two tumor-bearing mice models with subcutaneous injection or tail intravenous injection. Functionally, administration of CFG suppresses in situ tumor growth and distant lung metastasis. Subsequently, gas chromatography-mass spectrometry (GC-MS) was applied to determine the metabolic alterations among the plasma samples from these in vivo models. In the subcutaneous injection model, 26 distinguishable metabolites were identified and 12 metabolic pathways were reprogrammed. Meanwhile, 19 metabolites involved in 7 metabolic pathways showed significant differences in the tail intravenous injection model. Importantly, integrative metabolomics and transcriptomics analysis showed these metabolites were highly associated with galactose metabolism and fatty acid metabolism. This study suggests that CFG may suppress ovarian cancer cell proliferation and metastasis by regulating mitochondrion-related energy metabolisms.

14.
In Vitro Cell Dev Biol Anim ; 54(10): 692-704, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30367366

RESUMEN

How genomic DNA methylation and methyl CpG-binding protein 2 (MeCP2) gene expression affect the pathogenesis of systemic lupus erythematosus (SLE) remains poorly understood. Traditional Chinese medicine has a unique effect in the treatment of SLE patients. This study aimed to investigate the effect of Jieduquyuziyin prescription (JP)-treated rat serum on the gene expression of MeCP2 in Jurkat T cells and its role in the pathogenesis of SLE. Jurkat T cells were harvested, and drug-containing serum was prepared. The ferulic acid and paeoniflorin content in the drug-containing serum were determined by liquid chromatography-mass spectrometry (LC-MS/MS). 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays were used to screen the optimal concentration of drug-containing serum. The DNA methylation level in Jurkat T cells was detected with a Methylamp™ Total DNA Methylation Kit. The methylation status of the MeCP2 promoter region was detected using bisulfite modification and methylation-specific PCR (MSP). Real-time PCR was used to measure MeCP2 mRNA expression. Western blotting and flow cytometry were done to detect MeCP2 protein expression in Jurkat cell nuclei. Paeoniflorin and ferulic acid were detected in the drug-containing serum of JP-treated rats. The results showed that cell growth was affected in the high serum-containing drug group. The experimental results showed that JP and prednisone acetate increased the level of genomic DNA methylation and MeCP2 gene promoter region methylation in Jurkat cells. MeCP2 mRNA and protein levels were also increased in the JP and prednisone acetate groups. Furthermore, flow cytometry revealed that the expression of MeCP2 protein in Jurkat T cell nuclei was higher in the drug group than the blank control group, and these results were consistent with the western blot analysis results. Our study found that there is a negative correlation between drug-containing serum and cell survival rate. JP upregulated the levels of DNA methylation, MeCP2 mRNA and protein as effectively as prednisone acetate and thus may activate the MeCP2 gene by increasing the methylation level, thereby inhibiting the pathogenesis of SLE. Therefore, JP may potentially be used to treat SLE patients. The Jurkat T lymphocyte in vitro experiments provided a foundation to study the effects of JP on the lupus mouse CD4+ T cell methylation mechanism and to further explore the pathogenesis of SLE.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Proteína 2 de Unión a Metil-CpG/genética , Suero/metabolismo , Animales , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Metilación de ADN/genética , Humanos , Células Jurkat , Proteína 2 de Unión a Metil-CpG/metabolismo , Prednisona/farmacología , Regiones Promotoras Genéticas/genética , Unión Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley
15.
Microb Pathog ; 124: 223-229, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30149133

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disease. Interleukin-1 receptor-associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans and paeoniflorin has recently been reported to exhibit immunosuppressive properties. The aim of this study was to determine the effect of paeoniflorin on lipopolysaccharide (LPS)-triggered macrophage activation and and its role in LPS-induced IRAK1-nuclear factor κB (NF-κB) signaling pathways. Peritoneal macrophages from lupus-prone MRL/lpr mice and ICR mice were isolated, prepared and cultured. Cells were treated with LPS alone or LPS with paeoniflorin, and macrophage proliferation was analyzed using the CCK8 assay. The expression of IRAK1 in cells was analyzed by immunofluorescence staining. The level of gene expression of IRAK1, NF-κB, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by RT-PCR, and TNF-α, IL-6 levels in the cell supernatant were determined by ELISA. The protein expression of IRAK1 and downstream molecules tumor necrosis factor receptor-associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase (IKK), NF-kappa-B inhibitor alpha (IKBα), and NF-κB was detected by Western-blot analysis. Paeoniflorin was found to decrease the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of TNF-α and IL-6. Taken together, the data obtained indicate that paeoniflorin inhibits LPS-induced cell activation by inhibiting the IRAK1-NF-κB pathway in MRL/lpr mouse macrophages. Therefore, paeoniflorin may be a potential therapy for SLE.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Glucósidos/administración & dosificación , Quinasas Asociadas a Receptores de Interleucina-1/inmunología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Macrófagos Peritoneales/efectos de los fármacos , Monoterpenos/administración & dosificación , FN-kappa B/inmunología , Animales , Femenino , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Macrófagos Peritoneales/inmunología , Ratones , Ratones Endogámicos MRL lpr , FN-kappa B/genética , Paeonia/química , Raíces de Plantas/química , Transducción de Señal/efectos de los fármacos , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
16.
Sci Rep ; 8(1): 803, 2018 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-29339760

RESUMEN

Metallo-ß-lactamases (MBLs) are a group of enzymes that can inactivate most commonly used ß-lactam-based antibiotics. Among MBLs, New Delhi metallo-ß-lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by its success in rapidly disseminating worldwide since its first discovery. Here we report the biochemical and genetic characteristics of a novel MBL, ElBla2, from the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL. Enzymatic assays and secondary structure alignment also confirmed the high similarity between these two enzymes. Whole genome comparison of four Erythrobacter species showed that genes located upstream and downstream of elbla2 were highly conserved, which may indicate that elbla2 was lost during evolution. Furthermore, we predicted two prophages, 13 genomic islands and 25 open reading frames related to insertion sequences in the genome of E. litoralis HTCC 2594. However, unlike NDM-1, the chromosome encoded ElBla2 did not locate in or near these mobile genetic elements, indicating that it cannot transfer between strains. Finally, following our phylogenetic analysis, we suggest a reclassification of E. litoralis HTCC 2594 as a novel species: Erythrobacter sp. HTCC 2594.


Asunto(s)
Organismos Acuáticos/enzimología , Sphingomonadaceae/enzimología , beta-Lactamasas/análisis , beta-Lactamasas/genética , Islas Genómicas , Secuencias Repetitivas Esparcidas , Filogenia , Estructura Secundaria de Proteína , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Sphingomonadaceae/clasificación , Sphingomonadaceae/genética , beta-Lactamasas/química
17.
J Tradit Chin Med ; 38(5): 746-753, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-32185992

RESUMEN

OBJECTIVE: To assess the efficacy and safety in 105 patients with seasonal Influenza in Beijing, the mixture prepared with Chinese medicines follows the treatment regimen of releasing exterior cold and clearing interior heat. METHODS: Total 330 patients with seasonal influenza were enrolled and randomly and averagely divided into the Chinese herbal medicine, the western medicine and the Chinese patent medicine group. They were treated with Chinese medicine Oseltamivir Phosphate Capsules and the Scattering Wind and Resolving Toxins Capsules. The main efficacy indicators were the antifebrile onset time and recovery time of body temperature. The efficacy and safety of the mixture was scientifically evaluated. Comparisons of several variables were analyzed. RESULTS: Median antifebrile onset time of the Chinese herbal medicine group was significantly shorter than the western medicine group (P < 0.05) and the Chinese patent medicine group (P < 0.05). The median antifebrile recovery time of the Chinese herbal medicine group was significantly shorter than the Chinese patent medicine group (P < 0.05). The groups evaluated by TCM symptom pattern effect, both the Chinese herbal medicine group and Western Medicine group were better than the Chinese patent medicine group (P < 0.05). The disappearance rate of main symptoms and some minor symptom patterns of the Chinese herbal medicine group were higher than the other 2 groups. CONCLUSION: The mixture of releasing exterior cold and clearing interior heat could significantly shorten the fever time with safety.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Fiebre/tratamiento farmacológico , Gripe Humana/tratamiento farmacológico , Adulto , Temperatura Corporal/efectos de los fármacos , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Estaciones del Año , Resultado del Tratamiento
18.
Medicine (Baltimore) ; 96(46): e8537, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29145258

RESUMEN

BACKGROUND: Epidemiology studies suggested that shift work or night work may be linked to prostate cancer (PCa); the relationship, however, remains controversy. METHODS: PubMed, ScienceDirect, and Embase (Ovid) databases were searched before (started from the building of the databases) February 4, 2017 for eligible cohort studies. We pooled the evidence included by a random- or fixed-effect model, according to the heterogeneity. A predefined subgroup analysis was conducted to see the potential discrepancy between groups. Sensitivity analysis was used to test whether our results were stale. RESULTS: Nine cohort studies were eligible for meta-analysis with 2,570,790 male subjects. Our meta-analysis showed that, under the fixed-effect model, the pooled relevant risk (RR) of PCa was 1.05 (95% confidence interval [CI]: 1.00, 1.11; P = .06; I = 24.00%) for men who had ever engaged in night shift work; and under the random-effect model, the pooled RR was 1.08 (0.99, 1.17; P = .08; I = 24.00%). Subgroup analysis showed the RR of PCa among males in western countries was 1.05 (95% CI: 0.99, 1.11; P = .09; I = 0.00%), while among Asian countries it was 2.45 (95% CI: 1.19, 5.04; P = .02; I = 0.00%); and the RR was 1.04 (95% CI: 0.95, 1.14; P = .40; I = 29.20%) for the high-quality group compared with 1.21 (95% CI: 1.03, 1.41; P = .02; I = 0.00%) for the moderate/low-quality group. Sensitivity analysis showed robust results. CONCLUSIONS: Based on the current evidence of cohort studies, we found no obvious association between night shift work and PCa. However, our subgroup analysis suggests that night shift work may increase the risk of PCa in Asian men. Some evidence of a small study effect was observed in this meta-analysis.


Asunto(s)
Neoplasias de la Próstata/etiología , Horario de Trabajo por Turnos/efectos adversos , Humanos , Masculino , Riesgo , Factores de Riesgo
19.
Artículo en Inglés | MEDLINE | ID: mdl-28811829

RESUMEN

Colorectal cancer is one of the leading causes of tumor-associated death, and traditional Chinese medicine (TCM) classifies colorectal cancer into various subtypes mainly according to the symptomatic pattern identification (ZHENG). Here, we investigated the difference in metabolic profiles of serum by comparing colorectal cancer subjects with Nondeficiency (ND), Qi deficiency (QD), and Yin deficiency (YD). The ratio of subjects with carcinoembryonic antigen (CEA) was higher in YD pattern, and the ratio of subjects with carbohydrate antigen 19-9 (CA19-9) was higher both in YD and in QD, compared with ND. As a result of metabolomics analysis, twenty-five metabolites displayed differences between QD and ND, while twenty-eight metabolites displayed differences between YD and ND. The downregulated metabolites in QD/ND and YD/ND mainly include carbohydrates and the upregulated metabolites mainly include amino acids and fatty acids, suggesting conversion obstruction of carbohydrates, fatty acids, and amino acids occurs in patients with QD and YD compared with ND. Our results demonstrate that colorectal cancer patients with QD or YD were associated with metabolic disorders and the variations of serum metabolic profiles may serve as potential biochemical markers for diagnosis and prognosis of colorectal cancer patients displayed QD or YD patterns.

20.
Acad Radiol ; 24(10): 1216-1225, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28595876

RESUMEN

RATIONALE AND OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) and computed tomography (CT) in assessing small bowel (SB) Crohn disease (CD). MATERIALS AND METHODS: We systematically searched PubMed, Elsevier, ScienceDirect, Karger, Web of Science, Wiley Online Library, and Springer for studies in which CT or MRI were evaluated to assess SB CD. Bivariate random effect meta-analytic methods were used to estimate pooled sensitivity, specificity, and receiver operating characteristic curves. Diagnostic odds ratios (DORs) in a per-patient-based analysis were estimated. The area under the receiver operating characteristic curve was also calculated to measure the diagnostic accuracy. RESULTS: Twenty-one studies involving 913 patients were included in this meta-analysis. There was no significant difference observed between modalities. The diagnostic performances (lnDOR) for CT and MRI also showed no significant difference. Subgroup analysis was performed for MR imaging (MR enteroclysis, MR enterography, and CT enterography). The diagnostic performances (lnDOR) for MR enteroclysis, MR enterography, and CT enterography did not show a significant difference among them. No significant difference was found between these techniques. Deeks funnel plot asymmetry test for publication bias showed that no significant publication bias was observed in this analysis. CONCLUSIONS: This meta-analysis suggests that both MRI and CT have high diagnostic accuracy in detecting SB CD. MRI has the potential to be the first-line radiation-free modality for SB CD imaging.


Asunto(s)
Enfermedad de Crohn/diagnóstico por imagen , Intestino Delgado/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Humanos , Curva ROC , Sensibilidad y Especificidad
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