RESUMO
OBJECTIVES: Polymorphisms of IKAROS family zinc finger 1 (IKZF1) have been found to be associated with systemic lupus erythematosus (SLE) by genome-wide association studies (GWAS). The aim of the current study was to investigate the association between IKZF1 functional variants and lupus nephritis (LN) in a northern Han Chinese population and analyse their relationship with clinical and pathological phenotypes in LN. METHOD: The association between IKZF1 functional variants and LN was analysed for the lead variant rs1456896 with both GWAS and expression quantitative trait loci (eQTL) top hits in 500 LN patients and 500 healthy controls. Replication was conducted in an independent cohort comprising 798 LN patients and 704 healthy controls. Using the ENCODE (Encyclopedia of DNA Elements) databases, functional annotations and differential gene expression data were evaluated. RESULTS: A significant association between the single nuclear polymorphism (SNP) rs1456896 and susceptibility to LN was observed in the two different cohorts (p = 9.32 × 10-3 and p = 3.00 × 10-2) and reinforced in combination (p = 1.36 × 10-3). In silico analysis indicates that rs1456896 is a regulatory variant and lower mRNA expressions of IKZF1 were observed in both peripheral blood mononuclear cells (PBMCs) and renal biopsies from SLE patients compared to normal controls. Although patients with the protective genotype AA of rs1456896 seemed to have more pronounced clinical manifestations and a lower ratio of histological classes III and IV, no significant associations between rs1456896 genotypes and sub-phenotypes of LN were detected. CONCLUSIONS: Our results suggest that the rs1456896 A allele is associated with protective susceptibility to LN. However, this association did not seem to be implicated in the disease and histopathological severity of LN in the current population.
Assuntos
Povo Asiático/genética , Fator de Transcrição Ikaros/genética , Nefrite Lúpica/genética , Regiões 5' não Traduzidas/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Proteção , Índice de Gravidade de DoençaRESUMO
IgA nephropathy (IgAN) is a complex syndrome with high genetic heterogeneity. More recently, a genome-wide association study (GWAS) from Southern Han population revealed that variants within 8p23.1, where the DEFA genes encoding a-defensins assembled, were associated with susceptibility to IgAN. To replicate the association and fine-map the genetic variants, a case-control genetic study from an independent Northern Han cohort was conducted. A total of 60 single-nucleotide polymorphisms in a region spanning 350 kb encompassing the DEFA genes cluster were analyzed in 2096 individuals. Copy number variations of DEFA1A3 within the loci were also checked for the independent association. Functional significance of the associated variants was further examined by the in silico method as well as by cis-acting expression quantitative trait loci analysis with mRNA. It showed that 17 out of 60 (28.3%) variants were associated with susceptibility to IgAN. Two independent signals with functional potentials were discovered (rs2738058, P=4.64 × 10(-5), odds ratio (OR)=0.76, 95% confidence interval (CI) 0.66-0.87 and rs9644778, P=4.78 × 10(-3), OR=1.21, 95% CI 1.06-1.39). Besides, marginally significant association of rs9644778 risk genotype with lower proportion of gross hematuria (CC+CA vs AA 35.2% vs 30.2%, P=0.073) was observed. In conclusion, DEFA gene polymorphisms have potentially pathogenic roles in IgAN, and the role of mucosal immunity in the pathogenesis of IgAN has to be emphasized.
Assuntos
Povo Asiático/genética , Proteína DEFICIENS/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite por IGA/genética , Alelos , Estudos de Casos e Controles , China/epidemiologia , Variações do Número de Cópias de DNA , Feminino , Expressão Gênica , Ligação Genética , Genótipo , Glomerulonefrite por IGA/diagnóstico , Humanos , Desequilíbrio de Ligação , Masculino , Família Multigênica , Razão de Chances , Peptídeos Cíclicos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Índice de Gravidade de Doença , alfa-Defensinas/genéticaRESUMO
AIM: To investigate the feasibility of evaluating tumour lymphangiogenesis using magnetic resonance imaging (MRI) in vivo. MATERIALS AND METHODS: Water-soluble polyethylene glycol (PEG)-GoldMag nanoparticles were obtained by combining GoldMag with PEG. The PEG-GoldMag nanoparticles were bound to anti-podoplanin antibody (PodAb) to construct PEG-GoldMag-pod molecular probes targeting lymphatic endothelial cells (LECs). The characteristics of the PEG-GoldMag-pod nanoparticles were tested. Using these nanoparticles, tumour lymphangiogenesis was evaluated using MRI in vitro and in vivo. RESULTS: The average size of PEG-GoldMag nanoparticles was about 66.8 nm, and the nanoparticles were stably dispersed in the liquid phase for at least 15 days. After incubation for 24 h at different iron concentrations ranging from 5-45 µg/ml, the LECs were labelled with PEG-GoldMag-pod nanoparticles, in particular the breast cancer LECs. Dose-dependence was observed in the labelling efficiencies and MRI images of the labelled cells. In vitro, the labelling efficiencies and MRI images showed that the nanoparticles could detect podoplanin expression in LECs. In induced rat models of breast cancer, PEG-GoldMag-pod nanoparticles combined with lymphatic vessels were significantly detectable at MRI 60 min after nanoparticle administration, the signal intensity was negatively correlated with the lymphatic vessel density of breast cancer (r = -0.864, P = 0.000). CONCLUSIONS: The present study proves the feasibility of evaluating tumour lymphangiogenesis with MRI in vivo.
Assuntos
Neoplasias da Mama/patologia , Linfangiogênese , Imageamento por Ressonância Magnética/métodos , Nanopartículas Metálicas , Animais , Mama/patologia , Modelos Animais de Doenças , Feminino , Ouro , Humanos , Magnésio , Polietilenoglicóis , Ratos , Ratos WistarRESUMO
The study aimed to investigate the effects of dietary corn germ meal (CGM) levels on growth performance, carcass characteristic, serum biochemical indexes, meat physical and chemical quality, and standardized ileal digestibility of amino acids (SIDAA) in Pekin ducks from 10 to 42 d of age. A total of 420 ten-day-old Cherry Valley ducks were randomly allotted to 5 treatments with 6 replicate cages per treatment and 14 ducks per cages based on mean body weight. Five isonitrogenous and isocaloric experimental diets were formulated on a digestible amino acid basis to produce diets containing 0, 3, 6, 9, or 12% CGM. Results showed: 1) Compared with other groups, ducks fed 12% CGM significantly increased (P < 0.05) the feed to gain ratio. 2) Dietary CGM levels had no effect (P > 0.05) on the carcass traits and breast meat physical quality; but the content of crude protein presented a linear decrease (P < 0.05) in breast meat with increasing dietary CGM levels. 3) Serum biochemical indices (e.g., alanine aminotransferase, aspartate aminotransferase, glucose, high density lipoprotein cholesterol, total cholesterol, triglyceride, total protein, and urea) showed no significant differences among all groups (P > 0.05). 4) The levels of CGM had no significant effect on SIDAA of diets (P > 0.05), except for cysteine which showed a quadratic increase (P < 0.05). These results suggested that the optimal levels of CGM in diets for meat duck aged from 10 to 42 d should be below 9% based on feed to gain ratio and the content of crude protein in breast meat.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Patos , Aminoácidos/metabolismo , Ração Animal/análise , Animais , Galinhas/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Carne/análise , Zea mays/metabolismoRESUMO
The study aimed to investigate the effects of dietary distillers dried grains with solubles (DDGS) levels on growth performance, carcass characteristic, serum biochemical indexes, meat physical and chemical quality, nutrient utilization, and standardized ileal digestibility of amino acids (SIDAA) in Pekin ducks aged 11 to 42 d based on the evaluation of its SIDAA. A total of 560 eleven-day-old Cherry Valley ducks were randomly allotted to 5 treatments with 7 replicate pens per treatment and 16 ducks per pen based on the average body weight. Six isonitrogenous and isocaloric experimental diets were formulated on a digestible amino acid basis to produce diets containing 0, 5, 10, 15, and 20% DDGS, respectively. With increasing of dietary DDGS levels, a linear and quadratic reduction (P < 0.05) was observed in the body weight (BW) at d 42, average day gain (ADG) and average day feed intake (ADFI) from d 11 to 42, breast meat yield, the moisture and protein content in the breast meat, and dietary DM and EE utilization. Moreover, a linear and quadratic increase (P < 0.05) was observed in the b* value of the breast meat and serum total cholesterol and triglyceride concentrations. Compared with the control group, the group with 10% inclusion of DDGS exhibited no adverse effect on growth performance, carcass characteristics, serum biochemical indexes, meat physical and chemical quality, nutrient utilization, and the SIDAA of the diets (P > 0.05). These results suggested that 10% of corn DDGS can function as an alternative ingredient to corn and soybean meal, and the optimal levels of DDGS in the diets of ducks aged from 11 to 42 d depends more on its quality.
Assuntos
Glycine max , Zea mays , Animais , Aminoácidos/análise , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Composição Corporal , Peso Corporal , Galinhas , Dieta/veterinária , Patos , Grão Comestível/química , Zea mays/químicaRESUMO
OBJECTIVE: The aim of this study was to investigate the effect of 3-n-butylphthalide (NBP) on the apoptosis of nerve cells in vascular dementia (VaD) model rats caused by cerebral small vessel disease (CSVD), and to explore its regulatory mechanism. MATERIALS AND METHODS: The model of VaD was successfully established in rats by carotid artery ligation. All rats were randomly divided into three groups, including the sham operation group, model group and NBP group. The neurobehavioral score was used to verify whether the model was successfully established. The changes in learning and memory abilities of rats were detected via water maze experiment. The levels of Bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase-3 (Caspase-3) in the serum of rats was detected by enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was adopted to detect the apoptosis of nerve cells in brain tissues of rats. Moreover, the protein levels of phosphorylated phosphatidylinositol-3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in brain tissues of rats were measured using Western blotting. RESULTS: Compared with the sham operation group, the neurobehavioral score of rats increased significantly, whereas learning and memory abilities decreased markedly in the model group. The levels of Bax and Caspase-3 in rat serum were remarkably up-regulated, and the apoptosis rate of nerve cells in brain tissues of rats increased significantly in the model group as well. Meanwhile, the levels of phosphorylated PI3K and phosphorylated Akt were notably declined. Compared with the model group, the neurobehavioral score decreased markedly, while learning and memory abilities were remarkably improved in the NBP group. The levels of Bax and Caspase-3 in rat serum were significantly down-regulated, and the apoptosis rate of nerve cells in brain tissues of rats were reduced in the NBP group. Furthermore, the protein levels of phosphorylated PI3K and phosphorylated Akt were remarkably elevated in the NBP group. CONCLUSIONS: NBP can improve the morphology of brain tissue cells and the learning and memory abilities, and inhibit the apoptosis of nerve cells in VaD model rats with CSVD. The possible underlying mechanism may be related to the activation of the PI3K/Akt signaling pathway.
Assuntos
Apoptose/efeitos dos fármacos , Benzofuranos/farmacologia , Doenças de Pequenos Vasos Cerebrais/patologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteína Oncogênica v-akt/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/patologia , Caspase 3/metabolismo , Doenças de Pequenos Vasos Cerebrais/psicologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismoRESUMO
Objective To investigate the diagnostic value of electroencephalogram (EEG) complexity in patients with neurosyphilis by comparing the changes of electroencephalogram Lempel-Ziv complexity (EEG-LZC) before and after anti-syphilis treatment. Methods The EEG complexity of neurosyphilis patients diagnosed in our hospital from July in 2015 to June in 2017 was analyzed and compared with other diagnostic results such as serology examination and cerebrospinal fluid examination. Results A total of 27 patients were diagnosed, including 19 males and 8 females, of which 6 were mesenchymal(cerebrospinal membrane and meningeal vascular), 16 were parenchymal(paralytic dementia, spinal cord tuberculosis and optic neuropathy), and 5 were asymptomatic. After intensive anti-syphilis therapy, the LZC increased significantly in all patients while the trend and degree of change were consistent with other diagnostic results. Conclusion The LZC can be used as one of the diagnostic indexes meanwhile the trend and degree of its change can be used as the reference index of curative effect to neurosyphilis.
Assuntos
Antitreponêmicos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Eletroencefalografia , Neurossífilis/tratamento farmacológico , Neurossífilis/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurossífilis/diagnóstico , Processamento de Sinais Assistido por Computador , Resultado do TratamentoRESUMO
To elucidate the processes involved in the spatial and temporal maturation of spermatogenic cells in the testes of the soft-shelled turtle, Pelodiscus sinensis, we used a histological morphology method, TdT-mediated dUTP nick end-labeling (TUNEL) assay, the proliferating-cell nuclear antigen (PCNA), and electron microscopy. Seminiferous tubules from 100 turtles, normal for size of testes and semen quality, were collected during 10 months of a complete annual cycle (10 turtles/month). The seminiferous epithelium was spermatogenically active through the summer and fall, but quiescent throughout the rest of the year; germ cells progressed through spermatogenesis in a temporal rather than a spatial pattern, resulting in a single spermatogenic event that climaxed with one massive sperm release in November. The TUNEL method detected few apoptotic cells in spermatogenic testis, with much larger numbers during the spermatogenically quiescent phase. Spermatocytes were the most common germ cell types labeled by the TUNEL assay (a few spermatogonia were also labeled). Apoptotic spermatocytes had membrane blebbing and chromatin condensation during the resting phase, but not during active spermatogenesis. We inferred that accelerated apoptosis of spermatogonia and spermatocytes partly accounted for germ cell loss during the nonspermatogenic phase. The PCNA was expressed in nuclei of spermatogonia and primary spermatocytes during the spermatogenically active phase. During the regressive phase, PCNA-positive cells also included spermatogonia and spermatocytes, but the number of positive spermatocytes was less than that during the spermatogenically active phase. We concluded that seasonal variations in spermatogenesis in the soft-shelled turtle were both stage- and process-specific.
Assuntos
Apoptose/fisiologia , Proliferação de Células , Células Germinativas/citologia , Células Germinativas/fisiologia , Testículo/fisiologia , Tartarugas/fisiologia , Animais , Masculino , Estações do Ano , Testículo/citologiaRESUMO
Monoclinic NH(4)V(3)O(8) single-crystalline nanobelts with widths of 80-180 nm, thicknesses of 50-100 nm, and lengths up to tens of micrometers have been synthesized at large scale in an ammonium metavanadate solution by a templates/catalysts-free route. Such nanobelts grow along the direction of [010]. The individual NH(4)V(3)O(8) nanobelt exhibits nonlinear, symmetric current/voltage (I/V) characteristics, with a conductivity of 0.1-1 S/cm at room temperature and a dielectric constant of approximately 130. The dominant conduction mechanism is based on small polaron hopping due to ohmic mechanism at low electric field below 249 V/cm due to Schottky emission at medium electric field between 249 and 600 V/cm and due to the Poole-Frenkel emission mechanism at high field above 600 V/cm.
Assuntos
Nanopartículas/química , Nanotecnologia/métodos , Oxigênio/química , Vanádio/química , Catálise , Cristalização , Eletroquímica/métodos , Microscopia Eletrônica de Varredura , Modelos Estatísticos , Compostos de Amônio Quaternário/química , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Água/química , Difração de Raios XRESUMO
The feasibility of using the linear predictive coding (LPC) technique to replace the voicing sources of tracheoesophageal speech was explored. Four vowels, [i], [a], [e], [u], and one diphthong [ou], produced by two male and two female tracheoesophageal speakers were analyzed by the LPC autocorrelation method. Normalized prediction error functions were used to choose the algorithm and the control parameters of the analysis. Poles of the vocal tract transfer function were selected from frames whose normalized prediction errors were close to minimum with criteria derived from transfer functions of normally produced vowels. Vowels were synthesized with the reconstructed transfer function and a synthesized excitation input. Results of an identification task indicated that the synthesized vowels were highly intelligible, and the gender of the speaker was better identified from the synthesized vowels than from the original tracheoesophageal vowels.
Assuntos
Neoplasias Laríngeas/cirurgia , Laringectomia/reabilitação , Laringe Artificial/instrumentação , Voz Esofágica/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fonética , Espectrografia do Som , Inteligibilidade da FalaRESUMO
Spectra of vowels were analyzed to determine whether differences exist between the spectral slope of vowels produced by tracheoesophageal (TE) speakers and normal speakers and, if so, to quantify such differences. The linear predictive autocorrelation method was used to calculate smoothed spectra and the spectra were normalized with respect to a low frequency component. Comparisons between normalized spectral energy within a selected high frequency range revealed that energy within this frequency range for vowels produced by TE speakers was significantly higher than that produced by normal speakers. A least-square distance matching procedure was used to quantify speaker group differences in the spectral slope of vowels. Average spectra of vowels produced by the normal speakers could be matched to average spectra of vowels produced by the TE speakers by decreasing the spectral slope of their vowels by 2-3 dB/octave.
Assuntos
Voz Esofágica , Adulto , Feminino , Humanos , FonéticaRESUMO
An acoustical description of speech and voice produced by 10 female tracheoesophageal (TE) speakers is provided. In light of results from earlier descriptions based on male TE speakers, and based on t-test comparisons, the female speakers produced generally more perturbation in fundamental frequency. Potential factors affecting this increase were elapsed time since the laryngectomy and extent of the laryngectomy surgery. The data from this investigation, however, indicate that in oral reading the characteristics of TE speech, including F0, may be highly similar regardless of speaker gender.
Assuntos
Laringe Artificial , Caracteres Sexuais , Acústica da Fala , Voz Alaríngea , Fala , Idoso , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The present exploratory project was undertaken (a) to determine the relative strength of low-frequency energy in the output of one widely used electronic artificial larynx (Servox) and (b) to assess the relative strength of low-frequency energy in vowels produced by users of this type of artificial larynx. We hypothesized that the outputs of electronic artificial larynges and the vowels produced by laryngectomized users of these devices would be characterized by significant deficits in low-frequency energy level. Five users of electronic larynges and 10 normal speakers (5 female and 5 male) provided the speech samples. Results of spectral analyses indicated that there was a significant deficit in low-frequency energy both in the acoustic signals generated by a Servox electronic larynx and in vowels produced by laryngectomized users of this type of electronic larynx. Based on these findings, a second order filter was designed and implemented digitally to compensate for the observed deficit in low-frequency energy. A perceptual experiment was completed to evaluate the effect of low-frequency enhancement on perceived speech quality. Ninety-eight percent (+/- 2%) of the responses of listeners indicated that low-frequency enhanced speech samples had better vocal quality or were more pleasant to listen to than the original speech samples. We conclude that consideration for enhancing low-frequency characteristics is warranted in the design of improved prosthetic devices for alaryngeal speakers.