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1.
BMC Pediatr ; 24(1): 190, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493129

RESUMO

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD. METHODS: In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated. RESULTS: Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762-0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value. CONCLUSIONS: Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.


Assuntos
Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Estudos de Casos e Controles , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/genética , Metilação de DNA , Biomarcadores , Proteínas de Ligação ao Cálcio/genética , Proteínas Adaptadoras de Sinalização CARD/genética
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 575-583, 2024 Jun 15.
Artigo em Zh | MEDLINE | ID: mdl-38926373

RESUMO

OBJECTIVES: To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: A total of 31 children aged 4-6 years with OSAHS were prospectively enrolled as the test group, and 24 healthy children aged 4-6 years were included as the control group. Relevant clinical indicators were recorded. Fecal samples were collected, and non-targeted metabolomics analysis using liquid chromatography-mass spectrometry was performed to detect all metabolites. RESULTS: A total of 206 metabolites were detected, mainly amino acids and their derivatives. There was a significant difference in the overall composition of intestinal metabolites between the test and control groups (P<0.05). Eighteen different metabolites were selected, among which six (N-acetylmethionine, L-methionine, L-lysine, DL-phenylalanine, L-tyrosine, and L-isoleucine) had receiver operating characteristic curve areas greater than 0.7 for diagnosing OSAHS. Among them, N-acetylmethionine had the largest area under the curve, which was 0.807, with a sensitivity of 70.83% and a specificity of 80.65%. Correlation analysis between different metabolites and clinical indicators showed that there were positive correlations between the degree of tonsil enlargement and enterolactone, between uric acid and phenylacetaldehyde, between blood glucose and acetylmethionine, and between cholesterol and 9-bromodiphenyl and procaine (P<0.05). There were negative correlations between the degree of tonsil enlargement and N-methyltyramine, aspartate aminotransferase and indolepropionic acid and L-isoleucine, between alanine aminotransferase and DL-phenylalanine, between indolepropionic acid and L-isoleucine, between uric acid and hydroxyquinoline, and between urea nitrogen and N,N-dicyclohexylurea (P<0.05). The metabolic functional pathways affected by differential metabolites mainly included riboflavin metabolism, arginine and proline metabolism, pantothenic acid and coenzyme A biosynthesis, cysteine and methionine metabolism, lysine degradation and glutathione metabolism. CONCLUSIONS: Intestinal metabolites and metabolic functions are altered in children aged 4-6 years with OSAHS, primarily involving amino acid metabolism disorders. The screened differential intestinal metabolites have potential screening and diagnostic value as biomarkers for OSAHS.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Criança , Masculino , Pré-Escolar , Feminino , Apneia Obstrutiva do Sono/metabolismo , Intestinos , Metionina/metabolismo , Metionina/análise
3.
Opt Express ; 31(17): 27508-27519, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710824

RESUMO

A theoretical scheme to enhance the sum sideband generation (SSG) via double radiation pressure is proposed. In this scheme, both sides of the double-cavity system are driven by red and blue detuned pump lasers and frequency components are generated at the sum sideband through optomechanical nonlinear interaction. The results show that the efficiency of SSG can be improved with orders of magnitude. We further investigate the properties of SSG in resolved and unresolved sideband regimes. The efficiencies of upper sum sideband generation (USSG) and lower sum sideband generation (LSSG) are the equivalent in the unresolved sideband regime when the threshold condition is satisfied. It is worth noting that with the increase of the ratio between the dissipation rate of the cavity field and the decay rate of the mechanical resonator (MR), the amplitude of the LSSG can be superior to that of the USSG. Our scheme may provide a potential application in realizing the measurement of high-precision weak forces and quantum-sensitive sensing.

4.
Microvasc Res ; 147: 104478, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36682486

RESUMO

INTRODUCTION: Kawasaki disease (KD) is a systemic vasculitis that causes abnormalities in the coronary arteries. Interleukin (IL)-41 is a novel immunoregulatory cytokine involved in the pathogenesis of some inflammatory and immune-related diseases. However, the role of IL-41 in KD is unclear. The purpose of this study was to detect the expression of IL-41 in the plasma of children with KD and its relationship with the disease. METHODS: A total of 44 children with KD and 37 healthy controls (HC) were recruited for this study. Plasma concentrations of IL-41 were determined by ELISA. Correlations between plasma IL-41 levels and KD-related clinical parameters were analyzed by Pearson correlation and multivariate linear regression analysis. Receiver operating characteristic curve analysis was used to assess the clinical value of IL-41 in the diagnosis of KD. RESULTS: Our results showed that plasma IL-41 levels were significantly elevated in children with KD compared with HC. Correlation analysis demonstrated that IL-41 levels were positively correlated with D-dimer and N-terminal pro-B-type natriuretic peptide, and negatively correlated with IgM, mean corpuscular hemoglobin concentration, total protein, albumin and pre-albumin. Multivariable linear regression analysis revealed that IgM and mean corpuscular hemoglobin concentrations were associated with IL-41. Receiver operating characteristic curve analysis showed that the area under the curve of IL-41 was 0.7101, with IL-41 providing 88.64 % sensitivity and 54.05 % specificity. CONCLUSION: Our study indicated that plasma IL-41 levels in children with KD were significantly higher than those in HC, and may provide a potential diagnostic biomarker for KD.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Estudos de Casos e Controles , Interleucinas , Albuminas , Biomarcadores , Imunoglobulina M
5.
Analyst ; 148(18): 4414-4420, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37552114

RESUMO

As a crucial indicator in food and water safety testing, the detection of Escherichia coli plays a significant role in maintaining environmental sanitation and promoting public health. Herein, based on the electrochemical activity characteristics of E. coli, we established an enhanced electrochemiluminescence aptasensor for E. coli analysis. This study presents a new method for accurate identification by utilizing a double aptamer recognition system. Specifically, a nano-cadmium sulfide (CdS) modified aptamer was used for primary labeling, while a second aptamer was immobilized on a graphene/chitosan composite electrode for re-capture. The use of two aptamers improves the accuracy of the identification process. Furthermore, the application of an electrode potential facilitates continuous electron transfer between the electrode and electrochemically active microorganisms, resulting in an enhanced electroluminescence signal in relation to the metabolic status. This strategy possesses better sensitivity, accuracy, and stability, demonstrating its potential for E. coli analysis.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Grafite , Escherichia coli/metabolismo , Técnicas Eletroquímicas/métodos , Elétrons , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Grafite/química
6.
BMC Pediatr ; 23(1): 197, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37101156

RESUMO

PURPOSE: We investigated changes in plasma transfer RNA related fragments (tRF) in children with obstructive sleep apnea-hypopnea syndrome (OSAHS) and the potential value as a disease marker. METHODS: Firstly, we randomly selected five plasma samples from the case group and the control group for high-throughput RNA sequencing. Secondly, we screened one tRF with different expression between the two groups, amplified it by quantitative reverse transcription-PCR (qRT-PCR) and sequenced the amplified product. After confirming that the qRT-PCR results were consistent with the sequencing results and the sequence of the amplified product contained the original sequence of the tRF, we performed qRT-PCR on all samples. Then we analyzed the diagnostic value of the tRF and its correlation with some clinical data. RESULTS: A total of 50 OSAHS children and 38 control children were included in this study. There were significant differences in height, serum creatinine (SCR) and total cholesterol (TC) between the two groups. The plasma expression levels of tRF-21-U0EZY9X1B (tRF-21) were significantly different between the two groups. Receiver operating characteristic curve (ROC) showed that it had valuable diagnostic index, with area under the curve (AUC) of 0.773, 86.71% and 63.16% sensitivity and specificity. CONCLUSIONS: The expression levels of tRF-21 in the plasma of OSAHS children decreased significantly which were closely related to hemoglobin, mean corpuscular hemoglobin, triglyceride and creatine kinase-MB, may become novel biomarkers for the diagnosis of pediatric OSAHS.


Assuntos
Apneia Obstrutiva do Sono , Criança , Humanos , Biomarcadores , RNA de Transferência , Curva ROC , Sensibilidade e Especificidade , Apneia Obstrutiva do Sono/diagnóstico , Síndrome , Estudos de Casos e Controles
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(2): 217-221, 2023 Feb 10.
Artigo em Zh | MEDLINE | ID: mdl-36709944

RESUMO

OBJECTIVE: To explore the genetic basis for a child featuring short stature and postaxial polydactyly. METHODS: A child who presented at Ningbo Women & Children's Hospital in May 2021 due to the"discovery of growth retardation for more than two years" was selected as the subject. Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out for the child, and candidate variant was verified by Sanger sequencing of his family members. RESULTS: The child was found to harbor a heterozygous c.3670C>T (p.Q1224) variant of the GLI2 gene, which may lead to premature termination of protein translation. The variant was not detected in either parent. CONCLUSION: The child was diagnosed with Culler-Jones syndrome. The c.3670C>T (p.Q1224*) variant of the GLI2 gene probably underlay the disease in this child.


Assuntos
Polidactilia , Criança , Feminino , Humanos , Dedos , Mutação , Proteínas Nucleares/genética , Polidactilia/genética , Dedos do Pé , Proteína Gli2 com Dedos de Zinco/genética
8.
BMC Microbiol ; 22(1): 151, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672661

RESUMO

BACKGROUND: Leptospirosis is a significant emerging infectious disease worldwide. Rodents are considered to be the most critical hosts of Leptospira spp. Fujian Province is a region highly endemic for leptospirosis in China. However, the genetic diversity of leptospires circulating among rodents in Fujian is limited. RESULTS: The carrier status of rodents for Leptospira spp. was investigated by culture and serological detection in Fujian during 2018-2020. A total of 710 rodents, including 11 species, were trapped, with Rattus losea being the dominant trapped species (50.56%). Fourteen pathogenic Leptospira strains were obtained. Seven L. borgpetersenii serogroup Javanica strains belonging to ST143, 4 L. interrogans serogroup Icterohaemorrhagiae strains belonging to ST1 and ST17, 2 L. interrogans serogroup Bataviae strains belonging to ST96 and ST333, and 1 L. interrogans serogroup Pyrogenes strains belonging to ST332 were identified using 16S rDNA gene sequencing, microscopic agglutination test (MAT) and Multilocus sequence typing (MLST). L. borgpetersenii serogroup Javanica belonging to ST143 was the dominant type (50.00%). A total of 387 rodent serum samples were tested by MAT. Serum were considered positive for seroreactivity at a titer ≥ 1:160 against at least one serovar. A total of 90 (23.26%) serum samples tested positive, and four serogroups were identified, with Javanica being the dominant serogroup (87.78%), which was similar to the dominant serogroup isolated from rodents. This study demonstrates a high prevalence of leptospirosis in rodents and public health education among high-risk workers is highly recommended. CONCLUSIONS: R. losea was the dominant trapped rodent, and L. borgpetersenii serogroup Javanica ST143 was widely distributed among rodents in Fujian from 2018 to 2020. Despite the low number of isolates obtained from rodents, this study suggests that continuous epidemiological surveillance of the aetiological characteristics of pathogenic Leptospira in wild animal reservoirs may help reduce the possible risk of disease transmission.


Assuntos
Leptospira , Leptospirose , Animais , China/epidemiologia , Leptospirose/epidemiologia , Leptospirose/veterinária , Tipagem de Sequências Multilocus , Ratos , Roedores , Sorogrupo
9.
Genet Med ; 23(4): 669-678, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33402738

RESUMO

PURPOSE: To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. METHODS: De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations. RESULTS: The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts. CONCLUSION: We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.


Assuntos
Deficiências do Desenvolvimento , Deficiência Intelectual , Criança , China/epidemiologia , Aberrações Cromossômicas , Variações do Número de Cópias de DNA/genética , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética
10.
Biochem Biophys Res Commun ; 522(1): 14-20, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31735337

RESUMO

Diabetes mellitus is a metabolic disease characterized by an increase in blood glucose levels due to lack of insulin secretion. Previous studies have confirmed that PICK1 is critical for both ß-cell function and glucose homeostasis. The aim of this study was to investigate the role of PICK1 in response to high glucose-induced ß-cell dysfunction and the molecular mechanism of regulation of PICK1. We found that overexpression of PICK1 in db/db diabetic mice significantly improved glucose tolerance and increased insulin release. High glucose treatment of Min6 cells inhibited PICK1 expression, and overexpression of PICK1 protected against high glucose-induced pancreatic cell dysfunction. Activation of the PI3K/Akt pathway by PICK1 in Min6 cells resulted in increased GLUT2 expression and this increase was abolished by treatment with a PI3K-specific inhibitor. Further, we showed that expression of PICK1 is negatively regulated by miR-139-5p through directly targeting its 3'UTR. These data suggested that PICK1 may participate in the functional protection of pancreatic ß-cells through PI3K/Akt signaling, promote insulin secretion, and delay the progression of diabetes, and is negatively regulated by miR-139-5p, further clarifying the regulation of pancreatic ß-cell function.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Morte Celular , Glucose/metabolismo , Células Secretoras de Insulina/citologia , MicroRNAs/genética , Transdução de Sinais , Animais , Linhagem Celular , Dieta Hiperlipídica , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 2/metabolismo , Homeostase , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
11.
J Clin Lab Anal ; 33(5): e22874, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30843267

RESUMO

BACKGROUND: Kawasaki disease is a childhood systemic vasculitis that causes coronary artery abnormalities. The etiology remains unknown and there are no specific diagnostic tests. Circular non-coding RNAs are a special class of endogenous RNAs that display some characteristics of an ideal biomarker. However, few studies have examined the expression of circRNAs in the serum of Kawasaki disease (KD) patients. The aim of this study was to identify circRNAs in the serum that can serve as potential biomarkers for KD diagnosis. METHODS: The cases were children diagnosed with KD (n = 56). The controls comprised healthy children (n = 56). Blood was collected from the patients before and after intravenous immunoglobulin therapy, and from the healthy controls. Levels of circANRIL and hsa_circ_0123996 in the serum were measured by quantitative reverse transcription PCR. Then, the potential relationship between serum circRNA levels and patients' biochemical parameter levels was investigated. Receiver operating characteristic curves were constructed for evaluating the diagnostic value of these circRNAs. RESULTS: The serum levels of circANRIL were lower in patients with KD before therapy than in the controls, but became higher in the patients after therapy than before therapy. The serum levels of hsa_circ_0123996 were higher in patients with KD before therapy than in healthy controls. CONCLUSION: Our study indicated that the circANRIL and hsa_circ_0123996 levels in the serum of patients with KD were significantly different from those in healthy individuals. circANRIL and hsa_circ_0123996 may become potential biomarkers for early KD diagnosis.


Assuntos
Síndrome de Linfonodos Mucocutâneos/genética , RNA Circular/sangue , RNA Longo não Codificante/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Pré-Escolar , Feminino , Regulação da Expressão Gênica , Humanos , Imunoglobulinas/administração & dosagem , Imunoglobulinas/uso terapêutico , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , RNA Circular/genética , RNA Longo não Codificante/genética , Curva ROC
12.
BMC Pediatr ; 18(1): 305, 2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30236089

RESUMO

BACKGROUND: Exposure to air pollutants has been related to preterm birth, but little evidence can be available for PM2.5, O3 and CO in China. This study aimed to investigate the short-term effect of exposure to air pollutants on risk preterm birth during 2014-2016 in Ningbo, China. METHODS: We conducted a time-series study to evaluate the associations between daily preterm birth and major air pollutants (including PM2.5, PM10, SO2, NO2, O3 and CO) in Ningbo during 2014-2016. A General Additive Model extend Poisson regression was used to evaluate the relationship between preterm birth and air pollution with adjustment for time-trend, meteorological factors and day of the week (DOW). We also conducted a subgroup analysis by season and age. RESULTS: In this study, a total of 37,389 birth occurred between 2014 and 2016 from the Electronic Medical Records System of Ningbo Women and Children's Hospital, of which 5428 were verified as preterm birth. The single pollutant model suggested that lag effect of PM2.5, PM10, NO2 reached a peak at day 3 before delivery and day 6 for SO2, and no relationships were observed for O3 and preterm birth. Excess risks (95% confidence intervals) for an increase of IQR of air pollutant concentrations were 4.84 (95% CI: 1.77, 8.00) for PM2.5, 3.56 (95% CI: 0.07, 7.17) for PM10, 3.65 (95% CI: 0.86, 6.51) for SO2, 6.49 (95% CI: 1.86, 11.34) for NO2, - 0.90 (95% CI: -4.76, 3.11) for O3, and 3.36 (95% CI: 0.50, 6.30) for CO. Sensitivity analyses by exclusion of maternal age < 18 or > 35 years did not materially alter our results. CONCLUSIONS: This study indicates that short-term exposure to air pollutants (including PM2.5, PM10, SO2, NO2) are positively associated with risk of preterm birth in Ningbo, China.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Nascimento Prematuro/epidemiologia , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Monóxido de Carbono/efeitos adversos , China/epidemiologia , Humanos , Dióxido de Nitrogênio/efeitos adversos , Ozônio/efeitos adversos , Material Particulado/efeitos adversos , Fatores de Risco , Estações do Ano , Dióxido de Enxofre/efeitos adversos
13.
Proc Natl Acad Sci U S A ; 112(25): 7821-6, 2015 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-26056265

RESUMO

Over 30% of patients with amyotrophic lateral sclerosis (ALS) exhibit cognitive deficits indicative of frontotemporal dementia (FTD), suggesting a common pathogenesis for both diseases. Consistent with this hypothesis, neuronal and glial inclusions rich in TDP43, an essential RNA-binding protein, are found in the majority of those with ALS and FTD, and mutations in TDP43 and a related RNA-binding protein, FUS, cause familial ALS and FTD. TDP43 and FUS affect the splicing of thousands of transcripts, in some cases triggering nonsense-mediated mRNA decay (NMD), a highly conserved RNA degradation pathway. Here, we take advantage of a faithful primary neuronal model of ALS and FTD to investigate and characterize the role of human up-frameshift protein 1 (hUPF1), an RNA helicase and master regulator of NMD, in these disorders. We show that hUPF1 significantly protects mammalian neurons from both TDP43- and FUS-related toxicity. Expression of hUPF2, another essential component of NMD, also improves survival, whereas inhibiting NMD prevents rescue by hUPF1, suggesting that hUPF1 acts through NMD to enhance survival. These studies emphasize the importance of RNA metabolism in ALS and FTD, and identify a uniquely effective therapeutic strategy for these disorders.


Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Modelos Biológicos , Neurônios/efeitos dos fármacos , Transativadores/fisiologia , Sobrevivência Celular , Humanos , Fármacos Neuroprotetores/farmacologia , Degradação do RNAm Mediada por Códon sem Sentido , RNA Helicases
14.
Int Ophthalmol ; 38(1): 19-28, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28894971

RESUMO

PURPOSE: This study aimed to identify associated genes with primary open-angle glaucoma (POAG) and explore the potentially modular mechanism underlying POAG. METHODS: We downloaded gene expression profiles data GSE27276 from gene expression omnibus and identified differentially expressed genes between POAG patients and normal controls. Then, gene ontology analysis and kyoto encyclopedia of genes and genomes pathway enrichment were performed to predict the DEGs functions, followed with the construction, centrality analysis, and module mining of protein-protein interaction network. RESULTS: A total of 552 DEGs including 249 up-regulated and 303 down-regulated genes were identified. The up-regulated DEGs were significantly involved in cell adhesion molecule, while the down-regulated DEGs were significantly involved in complement and coagulation cascades. Centrality analysis screened out 20 genes, among which COL4A4, COL3A1, COL1A2, ITGB5, COL5A2, and COL5A1 were shared in ECM-receptor interaction and focal adhesion pathways. In the sub-network, COL5A2, COL8A2, and COL5A1 were significantly enriched in biological function of eye morphogenesis and eye development, while LAMA5, COL3A1, COL1A2, and COL5A1 were significantly enriched in vasculature development and blood vessel development. CONCLUSIONS: Six genes, including COL4A4, COL3A1, COL1A2, ITGB5, COL5A2, and COL5A1, ECM-receptor interaction and focal adhesion pathway, are potentially involved in the pathogenesis of POAG via participating in pathways of ECM-receptor interaction and focal adhesion.


Assuntos
Biologia Computacional/métodos , Glaucoma de Ângulo Aberto/genética , Transcriptoma , Estudos de Casos e Controles , Regulação para Baixo , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Cadeias beta de Integrinas/genética , Cadeias beta de Integrinas/metabolismo , Laminina/genética , Laminina/metabolismo , Regulação para Cima
15.
Protein Expr Purif ; 139: 71-77, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28602686

RESUMO

A GH11 xylanase gene (xyn11-1) cloned from saline-alkali soil was successfully expressed in Pichia pastoris GS115. The purified recombinant Xyn11-1 showed its maximal activity at pH 6.0, and retained more than 60.4% of activity at pH 10.0, with good pH stability. Its optimal temperature was 50 °C and it was stable after incubation for 1 h at 30 °C. Furthermore, Xyn11-1 was highly salt-tolerant, retaining more than 77.4% of activity in the presence of 0.25-4 M NaCl and displaying more than 47.2% relative activity after being incubated in the presence of 5 M NaCl at 37 °C for 10 min. In addition, 5 mM ß-Mercaptoethanol, Cu2+, Co2+, and Mn2+ increased the xylanase activity by 22.3%, 8.8%, 7.1%, and 4.4%, respectively. Significantly, 93.4% and 59.8% of the optimal activity was retained in the presence of 2% and 10% (v/v) ethanol, respectively. Under optimal conditions, the Km,Vmax, and Kcat value of Xyn11-1 for beechwood xylan were 3.7 mg ml-1, 101.0 µmol min-1 mg-1 and 42.1 s-1, respectively. Xyn11-1 is a strict endo-ß-1,4-xylanase, its main enzymatic products being xylotetraose and xylopentaose. Xyn11-1 is the first reported GH11 xylanase isolated from saline-alkali soil, and has excellent tolerance of high pH, high salt concentrations and ethanol, which indicates its great potential for basic research and industrial applications.


Assuntos
Endo-1,4-beta-Xilanases/metabolismo , Pichia/genética , Proteínas Recombinantes/metabolismo , Endo-1,4-beta-Xilanases/química , Endo-1,4-beta-Xilanases/genética , Estabilidade Enzimática , Etanol , Concentração de Íons de Hidrogênio , Hidrólise , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Cloreto de Sódio , Microbiologia do Solo , Especificidade por Substrato , Temperatura
16.
Int J Toxicol ; 36(6): 449-462, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29202623

RESUMO

ANX005 is a humanized immunoglobulin G4 recombinant antibody against C1q that inhibits its function as the initiating molecule of the classical complement cascade. The safety and tolerability of ANX005 are currently being evaluated in a phase I trial in healthy volunteers ( www.clinicaltrials.gov Identifier: NCT03010046). Inhibition of C1q can be applied therapeutically in a broad spectrum of diseases, including acute antibody-mediated autoimmune disease, such as Guillain-Barré syndrome (GBS), and in chronic diseases of the central nervous system involving complement-mediated neurodegeneration, such as Alzheimer's disease (AD). To support the clinical development of ANX005, several studies were conducted to assess the pharmacology, pharmacokinetics, and potential toxicity of ANX005. ANX-M1, the murine precursor of ANX005, functionally inhibits the classical complement cascade both in vitro and in vivo, to protect against disease pathology in mouse models of GBS and AD. Toxicology studies with ANX005, itself, showed that intravenous administration once weekly for 4 weeks was well tolerated in rats and monkeys, with no treatment-related adverse findings. Serum levels of ANX005 in monkeys correlate with a reduction in free C1q levels both in the serum and in the cerebrospinal fluid. In summary, ANX005 has shown proof of concept in in vitro and in vivo nonclinical pharmacology models, with no toxicity in the 4-week repeat-dose studies in rats and monkeys. The no observed adverse effect level was 200 mg/kg/dose, which is 200-fold higher than the first-in-human starting dose of 1 mg/kg in healthy volunteers.


Assuntos
Anticorpos Monoclonais Humanizados/toxicidade , Doenças Autoimunes/tratamento farmacológico , Complemento C1q/imunologia , Doenças Neurodegenerativas/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Autoimunes/imunologia , Complemento C1q/metabolismo , Via Clássica do Complemento/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Injeções Intravenosas , Macaca fascicularis , Masculino , Doenças Neurodegenerativas/imunologia , Ratos Sprague-Dawley , Especificidade da Espécie
17.
J Sci Food Agric ; 97(4): 1342-1348, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27381716

RESUMO

BACKGROUND: Contamination of food and feed by aflatoxin B1 (AFB1) poses serious economic and health problems worldwide, so the development of biological methods for effective AFB1 degradation is strongly required. RESULTS: Among three AFB1-degrading microorganisms isolated from moldy peanut, Fusarium sp. WCQ3361 could remove AFB1 extremely effectively, with a degradation ratio of 70.20% after 1 min and 95.38% after 24 h. Its degradation ratio was not much affected by temperature change (0-90 °C) and it also displayed excellent thermostability, maintaining 99.40% residual activity after boiling for 10 min. Since protease K could reduce the AFB1 degradation ratio by 55.15%, it is proposed that the effective component for AFB1 degradation is a protein. The AFB1 degradation ability of Fusarium sp. WCQ3361 was further verified by feed stock detoxification and the MTT test with HepG2 cells. In addition, no degradation products were detected by preliminary liquid chromatography/mass spectrometry, suggesting that AFB1 might be metabolized to products with different chemical characteristics from AFB1. CONCLUSION: Fusarium sp. WCQ3361 is the first reported AFB1 degradation fungus belonging to the genus Fusarium with broad working temperature range, excellent thermostability and high activity, which provides a potential highly useful solution for dealing with AFB1 contamination in the human diet and animal feed. © 2016 Society of Chemical Industry.


Assuntos
Aflatoxina B1/metabolismo , Arachis/microbiologia , Contaminação de Alimentos/prevenção & controle , Proteínas Fúngicas/farmacologia , Fusarium/química , Temperatura , Biodegradação Ambiental , Endopeptidase K/farmacologia , Proteínas Fúngicas/análise , Células Hep G2 , Humanos
18.
Arch Microbiol ; 198(7): 673-87, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27129539

RESUMO

Yersinia enterocolitica is the most diverse species among the Yersinia genera and shows more polymorphism, especially for the non-pathogenic strains. Individual non-pathogenic Y. enterocolitica strains are wrongly identified because of atypical phenotypes. In this study, we isolated an unusual Y. enterocolitica strain LC20 from Rattus norvegicus. The strain did not utilize urea and could not be classified as the biotype. API 20E identified Escherichia coli; however, it grew well at 25 °C, but E. coli grew well at 37 °C. We analyzed the genome of LC20 and found the whole chromosome of LC20 was collinear with Y. enterocolitica 8081, and the urease gene did not exist on the genome which is consistent with the result of API 20E. Also, the 16 S and 23 SrRNA gene of LC20 lay on a branch of Y. enterocolitica. Furthermore, the core-based and pan-based phylogenetic trees showed that LC20 was classified into the Y. enterocolitica cluster. Two plasmids (80 and 50 k) from LC20 shared low genetic homology with pYV from the Yersinia genus, one was an ancestral Yersinia plasmid and the other was novel encoding a number of transposases. Some pathogenic and non-pathogenic Y. enterocolitica-specific genes coexisted in LC20. Thus, although it could not be classified into any Y. enterocolitica biotype due to its special biochemical metabolism, we concluded the LC20 was a Y. enterocolitica strain because its genome was similar to other Y. enterocolitica and it might be a strain with many mutations and combinations emerging in the processes of its evolution.


Assuntos
Genoma Bacteriano/genética , Yersinia enterocolitica/classificação , Yersinia enterocolitica/genética , Animais , Sequência de Bases , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Escherichia coli/genética , Filogenia , Plasmídeos , RNA Ribossômico 16S/genética , RNA Ribossômico 23S/genética , Ratos , Ureia/metabolismo
19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 37(2): 230-3, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25936714

RESUMO

OBJECTIVE: To explore the role of cardiopulmonary bypass (CPB) with vacuum assisted venous drainage(VAVD)in the management of newborns with congenital heart diseases. METHODS: Total 15 newborns with congenital heart diseases (11 males and 4 females)underwent heart operations. Their age ranged from 2 days to 28 days [mean:(15.67 ± 2.22)days], and their body weight from 2.3 kg to 4.8 kg [mean: (3.75 ± 0.19)kg]. Sternal median incision was made to establish CPB,during which VAVD was applied for all the newborns. RESULTS: In these 15 newborns,the mean CPB time was from 50 minutes to 343 minutes [mean:(170.3 ± 26.6)minutes], and the mean aortic clamping time ranged from 20 minutes to 172 minutes [mean:(85.8 ± 14.6)minutes]. No macroscopic hematuria, inadequate drainage, or cannulation vena cava difficulty was observed during the procedures. All the newborns were successfully weaned from the machine. No neurological complication due to micro air embolus caused by negative pressure was noted. No vena cava infarction, thrombosis, or other complication was reported after the surgery, although one patient died after the surgery and another patient was discharged upon its family's own decision. CONCLUSIONS: VAVD is a safe, simple, and cost-effective technique. Appropriate negative pressure can the resistance during thinner venous intubation and thus speed up blood drainage,provide adequate perfusion flow,and reduce the pre-filling volume.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Drenagem , Ponte Cardiopulmonar , Feminino , Humanos , Recém-Nascido , Masculino , Vácuo , Veias
20.
BMC Genomics ; 15: 201, 2014 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-24628971

RESUMO

BACKGROUND: Yersinia enterocolitica outer membrane protein A (OmpA) is one of the major outer membrane proteins with high immunogenicity. We performed the polymorphism analysis for the outer membrane protein A and putative outer membrane protein A (p-ompA) family protein gene of 318 Y. enterocolitica strains. RESULTS: The data showed all the pathogenic strains and biotype 1A strains harboring ystB gene carried both ompA and p-ompA genes; parts of the biotype 1A strains not harboring ystB gene carried either ompA or p-ompA gene. In non-pathogenic strains (biotype 1A), distribution of the two genes and ystB were highly correlated, showing genetic polymorphism. The pathogenic and non-pathogenic, highly and weakly pathogenic strains were divided into different groups based on sequence analysis of two genes. Although the variations of the sequences, the translated proteins and predicted secondary or tertiary structures of OmpA and P-OmpA were similar. CONCLUSIONS: OmpA and p-ompA gene were highly conserved for pathogenic Y. enterocolitica. The distributions of two genes were correlated with ystB for biotype 1A strains. The polymorphism analysis results of the two genes probably due to different bio-serotypes of the strains, and reflected the dissemination of different bio-serotype clones of Y. enterocolitica.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Família Multigênica , Polimorfismo Genético , Yersinia enterocolitica/genética , Proteínas da Membrana Bacteriana Externa/química , Sequência de Bases , Códon , Mutação INDEL , Mutação , Fases de Leitura Aberta , Filogenia , Yersinia enterocolitica/metabolismo
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