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1.
Zool Res ; 41(1): 20-31, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31930784

RESUMO

There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts. Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface; however, studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models. Here, we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status. Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment. Furthermore, the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment, and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed. In addition to inducing aberrant morphology of small intestinal villi, the depletion of gut commensal bacteria led to increased proportions of CD3 + T, CD4 + T, and CD16 + NK cells in peripheral blood mononuclear cells (PBMCs), but decreased numbers of Treg and CD20 + B cells. The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes, including IL-13, VCAM1, and LGR4.


Assuntos
Disbiose/imunologia , Microbioma Gastrointestinal , Intestinos/anatomia & histologia , Macaca mulatta/microbiologia , Animais , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , DNA Bacteriano/genética , Fezes/microbiologia , Intestinos/microbiologia , Masculino
2.
Biomarkers ; 25(1): 94-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31762333

RESUMO

Background: Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term exposure at low dose has been seldom studied yet. The current study investigates the time-course change of the metabolomic profiles of urine following the low level long-term exposure of permethrin and identified biomarkers of the chronic toxicity of permethrin.Methods: Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD50) daily for consecutive 90 days. The urine samples from day 30, day 60, and day 90 after the first dosing were collected and analysed by 1H NMR spectrometry. Serum biochemical analysis was also carried out.Results: Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine-N-oxide. These biological markers indicated prominent kidney and liver toxicity induced by permethrin. However, there was no change in serum biochemical parameters for the toxicity, indicating that metabolomic approach was much more sensitive in detecting the chronic toxicity.Conclusion: The time-course alteration of metabolomic profiles of the urine based on 1H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.

3.
Gene ; 722: 144127, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525397

RESUMO

Complement factor H (CFH) serves as a major down-regulator in the complement system, often utilized by bacterial pathogens to evade complement attack. Yet, little is currently known about the genetic correlation of CFH polymorphisms with sepsis due to various microbial infections. A case-control method (488 septic patients and 527 healthy individuals) was carried out in this study to investigate the genetic relationship between CFH polymorphisms (rs3753394 C/T, rs1065489 G/T and rs1061170 C/T) and susceptibility to sepsis caused by bacterial infections in Chinese Han populations. Our findings indicated that the frequency of rs3753394 CT/TT genotype in the septic patients with P. aeruginosa was significantly higher than that in the control individuals (P = 0.033, OR = 2.668, 95%CI = 1.072-6.334). The rs3753394 T allele frequency in the P. aeruginosa-infected patients was significantly increased, compared to that in the healthy controls (P = 0.014, OR = 1.68, 95%CI = 1.118-2.538). Moreover, these significant differences of rs3753394 genotype and allele frequencies remained after multiple testing corrections [P (corr.) = 0.033 for genotype; P (corr.) = 0.033 for allele]. The current study highlighted the significance of CFH polymorphism rs3753394 as a potential biomarker for targeting P. aeruginosa infection in critically ill patients.


Assuntos
Predisposição Genética para Doença , Infecções por Pseudomonas/genética , Pseudomonas aeruginosa , Sepse/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/etnologia , Fator H do Complemento/genética , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/etnologia , Sepse/diagnóstico , Sepse/etnologia , Sepse/microbiologia
4.
Sci Rep ; 9(1): 16989, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740703

RESUMO

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing 1H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.

6.
Bioinformatics ; 35(7): 1094-1097, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30184051

RESUMO

MOTIVATION: Both ß-value and M-value have been used as metrics to measure methylation levels. The M-value is more statistically valid for the differential analysis of methylation levels. However, the ß-value is much more biologically interpretable and needs to be reported when M-value method is used for conducting differential methylation analysis. There is an urgent need to know how to interpret the degree of differential methylation from the M-value. In M-value linear regression model, differential methylation M-value ΔM can be easily obtained from the coefficient estimate, but it is not straightforward to get the differential methylation ß-value, Δß since it cannot be obtained from the coefficient alone. RESULTS: To fill the gap, we have built a bridge to connect the statistically sound M-value linear regression model and the biologically interpretable Δß. In this article, three methods were proposed to calculate differential methylation values, Δß from M-value linear regression model and compared with the Δß directly obtained from ß-value linear regression model. We showed that under the condition that M-value linear regression model is correct, the method M-model-coef is the best among the four methods. M-model-M-mean method works very well too. If the coefficients α0, α2,…αp are not given (as 'MethLAB' package), the M-model-M-mean method should be used. The Δß directly obtained from ß-value linear regression model can give very biased results, especially when M-values are not in (-2, 2) or ß-values are not in (0.2, 0.8). AVAILABILITY AND IMPLEMENTATION: The dataset for example is available at the National Center for Biotechnology Information Gene Expression Omnibus repository, GSE104778. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Metilação de DNA , Projetos de Pesquisa , Modelos Lineares
7.
J Cell Biochem ; 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30216513

RESUMO

Numerous studies have shown that the estrogen receptor beta (ERß) and interleukin 6 receptor (IL-6R) had interaction in many tumors, including lung cancer. Previous studies found that ERß5 exhibits a different biological function compared with the other subtypes of ERß. Therefore, this study mainly explores the interaction between ERß5 and IL-6R in the progression of lung cancer. We found that the expression of ERß5, IL-6 and glycoprotein 130 (GP130) were significantly increased (P < 0.001) and the 5-year survival rate with the co-expression of ERß5 and GP130 is significantly lower (P = 0.0315) in non-small cell lung cancer (NSCLC) patients. The cell proliferation, invasion, and cell cycle were markedly increased, and the cell apoptotic was markedly inhibited with the concurrent action of ERß5 and IL-6 in A549 cells (P < 0.05). In addition, the expression of ERß5, GP130, p-AKT, and p-44/42 MAPK was also significantly increased in A549 cells (P < 0.05). These results indicate that ERß5 and GP130 can synergistically promote the progression of NSCLC and maybe combined as an independent prognostic factor in patients. In addition, these results also provide a theoretical basis for the combined targeting therapy of ERß5 and GP130 in NSCLC.

8.
Medicine (Baltimore) ; 97(27): e11352, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29979415

RESUMO

The purpose was to evaluate the role of plasma microRNA-223 (miRNA-223) in risk and prognosis in sepsis patients, and its correlation with inflammatory markers.In this study, 187 sepsis patients from July 2015 to December 2016 were consecutively enrolled. Blood samples from septic patients and healthy controls (HCs) were collected, and plasma was separated for miRNA-223 expression detected by quantitative real-time PCR (qPCR). Enzyme-linked immune sorbent assay (ELISA) was performed to detect inflammatory markers.The results were as follows: miRNA-223 was highly expressed in sepsis patients compared to HCs (P < .001). Receiver operating characteristic (ROC) curve revealed miRNA-223 disclosed a good diagnostic value of sepsis with area under curve (AUC) of 0.754, 95% CI: 0.706-0.803. Sensitivity and specificity were 56.6% and 86.6% at the best cut-off point, respectively. Multivariate logistic analysis indicated that miRNA-223 could predict sepsis risk independently. Spearman's correlation disclosed that miRNA-223 relatively expression positively correlated with APCHE II score (r = 0.459, P < 0.001), CRP (r = 0.326, P < 0.001), TNFα (r = 0.325, P < 0.001), IL-1ß (r = 0.165, P = 0.024), IL-6 (r = 0.229, P = 0.002) and IL-8 (r = 0.154, P = 0.035), while it was negatively correlated with IL-10 (r = -0.289, P < 0.001). miRNA-223 expression in non-survivor was higher than that in survivor (P < 0.001). ROC curve revealed miRNA-223 could distinguish sepsis non-survivor form survivor with AUC of 0.600, 95% CI: 0.505-0.695. Sensitivity and specificity were 83.5% and 38.9% respectively at the best cut-off point.In conclusion, plasma miRNA-223 correlates with disease severity and inflammatory markers levels, and it might serve as a novel diagnostic and prognostic biomarker in sepsis patients.


Assuntos
MicroRNAs/sangue , Sepse/sangue , APACHE , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Risco , Sensibilidade e Especificidade , Sepse/diagnóstico , Sepse/genética
9.
Zool Res ; 38(3): 146-154, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28585438

RESUMO

Respirovirus infection can cause viral pneumonia and acute lung injury (ALI). The interleukin-1 (IL-1) family consists of proinflammatory cytokines that play essential roles in regulating immune and inflammatory responses in vivo. IL-1 signaling is associated with protection against respiratory influenza virus infection by mediation of the pulmonary anti-viral immune response and inflammation. We analyzed the infiltration lung immune leukocytes and cytokines that contribute to inflammatory lung pathology and mortality of fatal H1N1 virus-infected IL-1 receptor 1 (IL-1R1) deficient mice. Results showed that early innate immune cells and cytokine/chemokine dysregulation were observed with significantly decreased neutrophil infiltration and IL-6, TNF-α, G-CSF, KC, and MIP-2 cytokine levels in the bronchoalveolar lavage fluid of infected IL-1R1 -/- mice in comparison with that of wild type infected mice. The adaptive immune response against the H1N1 virus in IL-1R1 -/- mice was impaired with downregulated anti-viral Th1 cell, CD8+ cell, and antibody functions, which contributes to attenuated viral clearance. Histological analysis revealed reduced lung inflammation during early infection but severe lung pathology in late infection in IL-1R1 -/- mice compared with that in WT infected mice. Moreover, the infected IL-1R1 -/- mice showed markedly reduced neutrophil generation in bone marrow and neutrophil recruitment to the inflamed lung. Together, these results suggest that IL-1 signaling is associated with pulmonary anti-influenza immune response and inflammatory lung injury, particularly via the influence on neutrophil mobilization and inflammatory cytokine/chemokine production.


Assuntos
Citocinas/metabolismo , Regulação da Expressão Gênica/fisiologia , Vírus da Influenza A Subtipo H1N1 , Pulmão/citologia , Infecções por Orthomyxoviridae/virologia , Receptores Tipo I de Interleucina-1/metabolismo , Animais , Citocinas/genética , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/metabolismo , Receptores Tipo I de Interleucina-1/genética
10.
Chem Biol Interact ; 272: 21-27, 2017 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-28456543

RESUMO

Carbamates and pyrethroids are widely used pesticides. However, their joint toxicity at low doses with long-term exposure remains unknown. Therefore, we investigated the subchronic joint hepatotoxicity of the two representative pesticides within these two classes, i.e., propoxur (PR) and permethrin (PE) in rats. The male Wistar rats were orally treated with three different doses of PR, PE and their mixtures for 90 consecutive days. Liver weight, serum clinical chemistry parameters and histopathological changes were measured to access the hepatotoxicity. In addition, oxidative stress markers in liver were measured using biochemical assays. The results showed that PR reduced liver weight and lead to prominent liver histological changes. Moreover, PR dose-dependently induced lipid peroxidation and reduced superoxide dismutase activity. In contrast, PE induced a relatively mild hepatotoxicity. Intriguingly, the mixture of PR and PE did not reduce liver weight or increase serum aspartate transaminase activity. In addition, the mixture did not reduce the antioxidant enzyme activity as PR did. Thus, these results showed that PR induced prominent hepatotoxicity with subchronic exposure, and there is a potential antagonistic interaction between PR and PE on the oxidative damage in liver of rats.


Assuntos
Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Permetrina/toxicidade , Propoxur/toxicidade , Administração Oral , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
11.
Viruses ; 9(5)2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28489053

RESUMO

Data from EV-D68-infected patients demonstrate that pathological changes in the lower respiratory tract are principally characterized by severe respiratory illness in children and acute flaccid myelitis. However, lack of a suitable animal model for EV-D68 infection has limited the study on the pathogenesis of this critical pathogen, and the development of a vaccine. Ferrets have been widely used to evaluate respiratory virus infections. In the current study, we used EV-D68-infected ferrets as a potential animal to identify impersonal indices, involving clinical features and histopathological changes in the upper and lower respiratory tract (URT and LRT). The research results demonstrate that the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the viral load detection in the feces, nasal, and respiratory tracts, the infection and shedding of EV-D68 in the ferret model was confirmed, and these results were supported by the EV-D68 VP1 immunofluorescence confocal imaging with α2,6-linked sialic acid (SA) in lung tissues. Furthermore, we detected the inflammatory cytokine/chemokine expression level, which implied high expression levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs. These data indicate that systemic observation of responses following infection with EV-D68 in ferrets could be used as a model for EV-D68 infection and pathogenesis.


Assuntos
Modelos Animais de Doenças , Enterovirus Humano D/patogenicidade , Infecções por Enterovirus/virologia , Sistema Respiratório/fisiopatologia , Sistema Respiratório/virologia , Infecções Respiratórias/virologia , Animais , Proteínas do Capsídeo/ultraestrutura , Criança , Pré-Escolar , Citocinas/genética , Citocinas/imunologia , Enterovirus Humano D/imunologia , Enterovirus Humano D/isolamento & purificação , Infecções por Enterovirus/imunologia , Fezes/virologia , Furões , Imunofluorescência , Humanos , Interleucina-17/genética , Interleucina-5/genética , Interleucina-8/genética , Pulmão/imunologia , Pulmão/virologia , Nariz/virologia , Filogenia , Infecções Respiratórias/imunologia , Carga Viral
12.
Int J Mol Sci ; 18(4)2017 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-28441774

RESUMO

Perfluorooctane sulfonate (PFOS), a new kind of persistent organic pollutant, is widely distributed in the environment and exists in various organisms, where it is also a neurotoxic compound. However, the potential mechanism of its neurotoxicity is still unclear. To examine the role of epigenetics in the neurotoxicity induced by PFOS, SK-N-SH cells were treated with different concentrations of PFOS or control medium (0.1% DMSO) for 48 h. The mRNA levels of DNA methyltransferases (DNMTs) and Brain-derived neurotrophic factor (BDNF), microRNA-16, microRNA-22, and microRNA-30a-5p were detected by Quantitative PCR (QPCR). Enzyme Linked Immunosorbent Assay (ELISA) was used to measure the protein levels of BDNF, and a western blot was applied to analyze the protein levels of DNMTs. Bisulfite sequencing PCR (BSP) was used to detect the methylation status of the BDNF promoter I and IV. Results of MTT assays indicated that treatment with PFOS could lead to a significant decrease of cell viability, and the treated cells became shrunk. In addition, PFOS exposure decreased the expression of BDNF at mRNA and protein levels, increased the expression of microRNA-16, microRNA-22, microRNA-30a-5p, and decreased the expression of DNMT1 at mRNA and protein levels, but increased the expression of DNMT3b at mRNA and protein levels. Our results also demonstrate that PFOS exposure changes the methylation status of BDNF promoter I and IV. The findings of the present study suggest that methylation regulation of BDNF gene promoter and increases of BDNF-related-microRNA might underlie the mechanisms of PFOS-induced neurotoxicity.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Poluentes Ambientais/toxicidade , Epigênese Genética/efeitos dos fármacos , Fluorcarbonetos/toxicidade , Fator Neurotrófico Derivado do Encéfalo/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , DNA-Citosina Metilases/genética , DNA-Citosina Metilases/metabolismo , Ensaio de Imunoadsorção Enzimática , Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
13.
J Huazhong Univ Sci Technolog Med Sci ; 37(2): 226-230, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28397043

RESUMO

Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase to control elevated cholesterol, or hypercholesterolemia. Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis. Herein, we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock. In our study, rats were divided into a saline group, an LPS group and an LPS plus simvastatin group. Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg), with variations in left ventricular pressure recorded throughout. Ninety min after LPS injection, whole blood was collected from the inferior vena cava, and neutrophils were separated from the whole blood using separating medium. The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1). In addition, mesentery microcirculations of inlet diameter, outlet diameter and blood flow rate were measured in all three groups. The results indicated that simvastatin significantly promoted heart systolic function and increased the level of uPA while simultaneously inhibited the expression of PAI-1 as compared with LPS group. Moreover, simvastatin reversed the LPS-induced inhibition of mesentery microcirculation. Taken together, it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.


Assuntos
Lipopolissacarídeos/efeitos adversos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Choque Séptico/prevenção & controle , Sinvastatina/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Testes de Função Cardíaca/efeitos dos fármacos , Masculino , Microcirculação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Choque Séptico/induzido quimicamente , Choque Séptico/metabolismo , Sinvastatina/farmacologia
14.
Biochemistry ; 54(50): 7385-92, 2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26606397

RESUMO

Neuropathy target esterase (NTE) is an endoplasmic reticulum membrane-associated phospholipase B, which is essential for embryonic and nervous system development. However, the regulation of NTE at the protein level had not been thoroughly investigated. Our previous study showed that NTE was degraded not only by the macroautophagy-lysosome pathway but also by the ubiquitin-proteasome pathway. Here we further reveal that androgen receptor-associated protein 54 (ARA54) regulated the ubiquitin-proteasome degradation of NTE. We find that deletion of the regulatory domain of NTE, which possesses a putative destruction box and thus is essential for its degradation by the proteasome, prevented its degradation by the proteasome. In addition, we demonstrate that ARA54, which has a RING finger domain and E3 ligase activity, interacts directly with NTE. Overexpression of ARA54 downregulates the protein level of NTE, and knockdown of ARA54 inhibits the degradation of NTE. The mutation in the RING domain of ARA54 blocks the degradation of NTE by ARA54, which indicates that the RING domain is essential for ARA54's E3 activity. These findings suggest that ARA54 acts as the ubiquitin ligase to regulate the ubiquitin-proteasome degradation of NTE.


Assuntos
Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Animais , Células COS , Linhagem Celular Tumoral , Humanos , Proteólise
15.
Zhonghua Yi Xue Za Zhi ; 95(9): 659-62, 2015 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-25976045

RESUMO

OBJECTIVE: To explore the incidence and species distribution of catheter-related bloodstream infection (CRBSI) in intensive care unit (ICU) at our hospital and analyze the risk factors for CRBSI. METHODS: Hospitalized patients microbiologically diagnosed as CRBSI were recruited from January 2012 to June 2013. And the clinical data were collected retrospectively and analyzed by software IBM SPSS 19.0. RESULTS: Among 67 patients diagnosed as nosocomial CRBSI, 24 cases (35.8%) died while 43 survived. And a total of 81 strains were detected, including 42 Gram-positive (G⁺) bacteria (51.9%), 36 Gram-negative (G⁻) bacteria (44.4%) and 3 fungi (3.7%).The predominant pathogenic G⁺ and G⁻ bacteria were Staphylococcus epidermidis and Acinetobacter baumannii respectively. With multiple Logistic regressions, age ≥ 65 years, higher acute physiology & chronic health evaluation II (APACHE II) score and polymicrobial CRBSI were independent predictors of worse outcomes. CONCLUSION: The recent prevalent pathogens of CRBSI in ICU are S.epidermidis and A.baumannii. Advanced age, disease severity and polymicrobial CRBSI are significant independent risk factor of mortality for CRBSI patients in ICU.


Assuntos
Bacteriemia , Infecções Relacionadas a Cateter , Infecção Hospitalar , Unidades de Terapia Intensiva , Humanos , Incidência , Modelos Logísticos , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco
16.
Dongwuxue Yanjiu ; 35(6): 485-91, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25465084

RESUMO

Coxsackie virus A16 (CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease (HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews (Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.


Assuntos
Infecções por Coxsackievirus/veterinária , Enterovirus/fisiologia , Tupaiidae , Animais , Antígenos Virais , Infecções por Coxsackievirus/patologia , Infecções por Coxsackievirus/virologia , Feminino , Distribuição Tecidual , Replicação Viral
17.
Neurol India ; 62(5): 498-502, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25387618

RESUMO

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a highly sensitive marker that reflects increased inflammation and is positively correlated with pro-inflammatory biomarkers. The aim of this prospective observational study was to explore the relationship between the plasma concentration of suPAR and traumatic brain injury (TBI). MATERIALS AND METHODS: In all 112 patients with TBI were included. Patients coming within 12 h whose highest abbreviated injury score (AIS) was 3 or less (other than head injury) were considered to be isolated TBI. Blood samples were obtained on admission. In all ninety healthy volunteers were enrolled as control group. Levels of plasma suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions. Plasma D-dimer was measured and Glasgow Coma Scale (GCS) score was assessed at the same time. RESULTS: Plasma suPAR values were statistically significantly higher in TBI patients than in controls (patients; 14.89 ± 6.94, controls; 2.79 ± 0.69, P < 0.01). The suPAR levels were strongly associated with the severity of TBI patients. The suPAR levels increased in association with the severity of brain injury, significance being found among all three groups: severe, moderate and mild TBI. The suPAR levels in non-survivals were significantly increased compared to the survivals (P < 0.05). Plasma levels of suPAR were strongly correlated to the GCS score (r = -0.854) and the levels of D-dimer (r = 0.753, both P < 0.01). Receiver operating characteristic curve (ROC) analysis of suPAR levels indicated that suPAR values had a high diagnostic specificity and sensitivity to differentiate survivals from non-survivals, the area underneath the ROC curve (AUROC) was 0.801 (95% CI: 0.698-0.903). The optimal suPAR cut-off value in predicting mortality was 15.70 ng/ml (sensitivity: 70.4%; specificity: 65.9%). CONCLUSIONS: Plasma levels of suPAR are elevated in TBI patients. Prognosis was worse in the patient group with elevated suPAR. High suPAR levels indicate a poorer prognosis in TBI patients.


Assuntos
Lesões Encefálicas/sangue , Lesões Encefálicas/diagnóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Idoso , Biomarcadores/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade
18.
Mol Cell Biochem ; 396(1-2): 33-40, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24990248

RESUMO

Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus ester and has been widely used in industry. It is found that TOCP induced delayed neurotoxicity in humans and sensitive animal species. However, the mechanism of TOCP-induced neural cytotoxicity remains unclear. In this study, we studied whether autophagy is involved in TOCP-induced neural cytotoxicity in human neuroblastoma SH-SY5Y cells. We found that 0.5 and 1.0 mM TOCP treatment significantly increased the ectopic accumulation of microtubule-associated protein 1 light chain 3 (LC3)-immunopositive puncta, Beclin 1, and LC3-II/LC3-I levels in SH-SY5Y cells in a dose-dependent manner. Notably, by monodansylcadaverine staining method, we found abundant punctate fluorescent acidic vesicular organelles in TOCP-treated cells. Furthermore, ultrastructural observation under the transmission electron microscope indicated that the cytoplasm was occupied by autophagosomes in TOCP-treated SH-SY5Y cells. Thus, these results suggest that TOCP may induce autophagy, and autophagy may be involved in the development of TOCP-induced neural cytotoxicity.


Assuntos
Autofagia/efeitos dos fármacos , Neuroblastoma/patologia , Tritolil Fosfatos/toxicidade , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Linhagem Celular Tumoral/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Citoplasma/ultraestrutura , Relação Dose-Resposta a Droga , Humanos , Proteínas de Membrana/metabolismo , Microscopia Eletrônica de Transmissão , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Síndromes Neurotóxicas/patologia , Fagossomos/efeitos dos fármacos , Fagossomos/ultraestrutura , Tritolil Fosfatos/administração & dosagem
19.
Environ Toxicol ; 29(10): 1193-200, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23418109

RESUMO

Anticholinesterase pesticides have been widely used in agricultural and domestic settings and can be detected in the environment after long-term use. Although the acute toxic effects of chlorpyrifos and carbaryl have been well described, little is known about the chronic toxicity of the pesticides mixture. To investigate their chronic neurotoxicity, Wistar rats were exposed to chlorpyrifos, carbaryl, and their mixture (MIX) for 90 consecutive days. The activities of serum cholinesterase (ChE) as well as acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in nerve tissues were determined. Furthermore, the histopathological examination was carried out. The results showed that ChE activity significantly decreased in all treated rats except the rats treated with low dose carbaryl. Treatment with middle- and high-dose chlorpyrifos and MIX in rats significantly inhibited AChE activity in the central nervous tissues, whereas treatment with carbaryl alone did not. In sciatic nerve, AChE activity was significantly inhibited by high-dose carbaryl and MIX, but not by chlorpyrifos alone. No significant NTE inhibition was observed in all treatment groups. Histopathological examination revealed that both chlorpyrifos and MIX treatment induced hippocampal damage. However, no obvious hippocampal damage was found in carbaryl-treated rats. Carbaryl and MIX, but not chlorpyrifos alone, induced pathological damage of sciatic nerve. Taken together, all of the results indicated that chlorpyrifos and carbaryl have different toxicological target tissues in nervous system and showed corresponding effects in the nervous tissues, which may reflect the different sensitivity of central and peripheral nervous tissues to different pesticides individually and in combination.


Assuntos
Carbaril/toxicidade , Clorpirifos/toxicidade , Inibidores da Colinesterase/toxicidade , Hipocampo/efeitos dos fármacos , Praguicidas/toxicidade , Nervo Isquiático/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Animais , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ratos , Ratos Wistar , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia
20.
Sci China Life Sci ; 56(12): 1124-33, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24302293

RESUMO

Studies of herpes simplex virus type 1 (HSV-1) infection have shown that many known and unknown cellular molecules involved in viral proliferation are up-regulated following HSV-1 infection. In this study, using two-dimensional polyacrylamide gel electrophoresis, we found that the expression of the HSV-1 infection response repressive protein (HIRRP, GI 16552881) was up-regulated in human L02 cells infected with HSV-1. HIRRP, an unknown protein, was initially localized in the cytoplasm and then translocated into the nucleus of HSV-1-infected cells. Further analysis showed that HIRRP represses HSV-1 proliferation by inhibiting transcription of the viral genome by interacting with the cellular transcription factor, ATF5, via its N-terminal domain. ATF5 represses the transcription of many host genes but can also act as an activator of genes containing a specific motif. We found that ATF5 promotes the proliferation of HSV-1 via a potential mechanism by which ATF5 enhances the transcription of viral genes during the course of an HSV-1 infection; HIRRP then induces feedback repression of this transcription by interacting with ATF5.


Assuntos
Proteínas de Transporte/fisiologia , Herpesvirus Humano 1/fisiologia , Proteínas Virais/fisiologia , Fatores Ativadores da Transcrição/química , Fatores Ativadores da Transcrição/genética , Fatores Ativadores da Transcrição/fisiologia , Animais , Sequência de Bases , Proteínas de Transporte/química , Proteínas de Transporte/genética , Linhagem Celular , Núcleo Celular/metabolismo , Citoplasma/metabolismo , DNA Viral/genética , DNA Viral/metabolismo , Eletroforese em Gel Bidimensional , Técnicas de Silenciamento de Genes , Genoma Viral , Células HEK293 , Células HeLa , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/patogenicidade , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Dados de Sequência Molecular , Domínios e Motivos de Interação entre Proteínas , Regulação para Cima , Células Vero , Proteínas Virais/química , Proteínas Virais/genética , Replicação Viral/genética , Replicação Viral/fisiologia
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