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1.
Food Chem ; 308: 125650, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31655477

RESUMO

This study aimed at investigating the formation and accumulation of 16 reactive aldehydes in clam (Ruditapes philippinarum) during oil frying in both the tissue and the oil using an HPLC-ESI-MS/MS methodology. After processing, the accumulation of acrolein, crotonaldehyde, pentanal, trans-2-hexenal, hexanal, trans, trans-2,4-heptadienal, heptanal, nonanal, trans, trans-2,4-decadienal and 4-hydroxy-2-nonenal was most noticeable in both fried clam and frying oil. Most of the aldehyde species showed a time- and temperature-dependent manner of formation and accumulation during frying due to continuous oxidative degradation under conditions employed. However, several species of aldehyde such as acrolein and trans-2-pentenal slightly decreased at higher temperatures and/or longer frying times, which may be due to the imbalance toward disappearance of aldehydes resulting from their evaporation under the extreme conditions. Presence of natural polyphenols in bamboo leaves significantly prevented the formation of aldehydes in both fried clam and frying oil due to their antioxidant activity (P < 0.05).

2.
Cancer Lett ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31705929

RESUMO

Dysregulation of long noncoding RNA (lncRNA) H19 has been implicated in hepatocellular carcinoma (HCC), but the concrete regulatory mechanism is lack of research. We mined gene expression profiles of 457 HCC samples from TCGA and TJMUCH cohorts and further validated in 64 FFPE HCC tissues. LncRNA H19 overexpression in situ was significantly correlated with poor prognosis of HCC patients, which induced EMT, promoted stemness and accelerated invasion of HCC cells in vitro. Co-expression network analysis indicated lncRNA H19 negatively correlated with miR-193b and positively correlated with MAPK1 gene, which implicated that lncRNA H19 served as a sponge molecule to hijack miR-193b and protect MAPK1. Forced overexpression of H19 attenuated miR-193b-mediated inhibition on multiple driver oncogenes (EGFR, KRAS, PTEN and IGF1R) and MAPK1 gene, thus triggered EMT and stem cell transformation in HCC. LncRNA H19 positively correlated with CD68+ TAMs in situ. TAMs-induced lncRNA H19 promotes HCC aggressiveness via triggering and activating the miR-193b/MAPK1 axis, mediates the crosstalk between HCC and immunological microenvironment, and causes poor clinical outcomes. LncRNA H19 is a valuable predictive biomarker and potential therapeutic target in HCC.

3.
Org Biomol Chem ; 17(41): 9200-9208, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31596301

RESUMO

A highly efficient domino aza-MIRC (Michael Induced Ring Closure) reaction between barbiturate-derived alkenes and N-alkoxy α-haloamides has been achieved in moderate to excellent yields. This reaction proceeds smoothly under mild conditions via a domino aza-Michael addition/intramolecular SN2 sequence, providing a practical tool in the synthesis of bioactive molecules spirobarbiturate-3-pyrrolidinones.

4.
Parasite ; 26: 58, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535970

RESUMO

Toxoplasma gondii infection is prevalent in humans and animals worldwide. In this study, recombinant eukaryotic expression plasmids (pVAX-GRA24, pVAX-GRA25 and pVAX-MIC6) were constructed, and then injected into Kunming mice intramuscularly, as cocktailed plasmids or as single-gene plasmids. We evaluated immune protective responses by detecting the titer of antibodies and cytokine production of IFN-γ, IL-2, IL-4, IL-10, IL-12 and IL-23, the percentages of the subclasses of T lymphocytes, as well as the records of the survival time and cyst decrement in the brain of the mouse model after challenge with the T. gondii RH and Pru strains, respectively. Compared with the control groups, antibody and cytokine production were significantly increased, while the survival times of mice in all immunized groups were also prolonged, and the number of T. gondii cysts in their brains were decreased significantly (29.03% for pVAX-GRA24; 40.88% for pVAX-GRA25; 37.70% for pVAX-MIC6; 48.06% for pVAX-GRA24 + pVAX-GRA25; and 55.37% for pVAX-GRA24 + pVAX-GRA25 + pVAX-MIC6). The mouse group immunized with the three-gene cocktail (TgGRA24 + TgGRA25 + TgMIC6) had better performance in each detection index than the mouse groups immunized with the two-gene cocktail of TgGRA24 + TgGRA25, which was better than that in the group immunized with the single gene vaccine of TgGRA24, TgMIC6 or TgGRA25. In conclusion, TgGRA24 or TgGRA25 may be good vaccine candidates against T. gondii infection, but the three-gene cocktail of TgGRA24, TgMIC6 and TgGRA25 may induce the strongest protective immunity. Further studies of multi-antigenic DNA vaccines or cocktailed vaccines against T. gondii infection are necessary.

5.
Appl Opt ; 58(21): 5687-5694, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503870

RESUMO

The Integrated Laser Communication/Ranging System, which uses a coded signal as the ranging information carrier, is of great importance to the next large-capacity inter-satellite information network. In this paper, a system design with a high-sensitivity feedback-homodyne detection scheme and an asynchronous ranging algorithm is demonstrated with real-time field-programmable gate array-implementation (FPGA). The parallel fast Fourier transformation (FFT) estimation is applied to improve the speed and the range of the wavelength drift tracking, which can handle a dynamic wavelength drift up to 2.4 pm/s (300 MHz/s). Meanwhile, for clock sources with subtle dynamic frequency offset and sufficient stability, the proposed fractional symbol ranging method is proven to achieve millimeter-level measurement accuracy. The designed system is shown to perform well in terms of both laser linewidth tolerance and noise resistance.

6.
J Immunol Res ; 2019: 7597382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534976

RESUMO

Background and Objective: Diabetic neuropathic pain (DNP) is a common complication associated with diabetes. Currently, its underlying pathomechanism remains unknown. Studies have revealed that the recruitment of blood monocyte-derived macrophages (MDMs) to the spinal cord plays a pivotal role in different models of central nervous system injury. Therefore, the present study aimed at exploring the infiltration and function of MDMs in DNP using a mice model. Methods: Diabetes was induced using streptozotocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Quantitative analysis of CD11b was performed and visualized by immunofluorescence. Spinal cord cells were isolated from myelin and debris by Percoll gradient. Flow cytometry was used to label CD11b and CD45 antibodies to differentiate MDMs (CD45highCD11b+) from resident microglia (CD45lowCD11b+). Mice were injected with clodronate liposomes to investigate the role of MDMs in DNP. The successful depletion of monocytes was determined by flow cytometry. Results: The DNP mice model was successfully established. Compared with nondiabetic mice, diabetic mice displayed a markedly higher level of CD11b immunofluorescence in the spinal cord. The number of CD11b-positive microglia/macrophages gradually increased over the 28 days of testing after STZ injection, and a significant increase was observed on Day 14 (P < 0.01) and 28 (P < 0.01). Further analysis by flow cytometry showed that the infiltration of peripheral macrophages began to increase in 2 weeks (P < 0.001) and reached a maximum at 4 weeks (P < 0.001) post-STZ injection compared to the control. The depletion of MDMs by clodronate liposomes alleviated diabetes-induced tactile allodynia (P < 0.05) and reduced the infiltration of MDMs (P < 0.001) as well as the expression of IL-1ß and TNF-α in the spinal cord (P < 0.05). Conclusions: The infiltration of blood MDMs in the spinal cord may promote the development of painful neuropathy in diabetes.

7.
J Ovarian Res ; 12(1): 79, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470880

RESUMO

OBJECTIVE: To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. METHODS: This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. RESULTS: The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615-0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054-1.190, p < 0.001), presence of adenomyosis (RR: 1.629, 95% CI: 1.008-2.630, p = 0.046), CA125 level (RR: 1.856, 95% CI: 1.072-3.214, p = 0.021) and severity of dysmenorrhea. The severity of dysmenorrhea (RR: 1.711, 95% CI: 1.175-2.493, p = 0.005) and postoperative pregnancy (RR: 0.649, 95% CI: 0.460-0.914, p = 0.013) were significantly correlated with endometrioma recurrence in the multivariate analysis. No significant associations were found between the recurrence rate and gravida, parity, body mass index, infertility, leiomyoma presence, the size of ovarian endometrioma, the presence of deep infiltrating endometriosis, disease stage or postoperative medication. CONCLUSIONS: The severity of dysmenorrhea and postoperative pregnancy were independent risk factors for the recurrence of ovarian endometriomas after surgery during the long-time follow up.

8.
Clin Exp Rheumatol ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287402

RESUMO

OBJECTIVES: To summarise the clinical data of adult-onset Still's disease (AOSD) patients and analyse their clinical manifestations, predictors for the formation and prognosis of macrophage activation syndrome (MAS). METHODS: A retrospective analysis was performed on the clinical data of 182 AOSD hospitalised patients from the Department of Rheumatology of the First Affiliated Hospital of Zhengzhou University, China from January 2012 to August 2018, including 11 patients with pathogenesis of MAS. RESULTS: Compared with the patients without MAS, the patients with MAS had a higher incidence of splenomegaly and pericarditis at the initial diagnosis of AOSD. The number of platelets (PLT) and the concentration of fibrinogen (FIB), D-Dimer and ferritin were significantly higher in AOSD-MAS patients. Multivariate regression analysis showed that splenomegaly (OR: 5.748, 95% CI: 1.378-23.984, p=0.016), pericarditis (OR: 6.492, 95% CI: 1.43-29.461, p=0.015), and ferritin >2000 µg/L (OR: 4.715, 95% CI: 1.12-19.86, p=0.035) were risk factors for MAS. Survival analysis indicated that the mortality of AOSD-MAS patients was significantly higher than patients without MAS. CONCLUSIONS: Splenomegaly, pericarditis and elevated ferritin concentration are risk factors for MAS formation in AOSD patients. MAS resulted in a significant decrease in the survival rate of the AOSD patients.

9.
Curr Drug Metab ; 20(7): 556-574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237211

RESUMO

BACKGROUND: The representative cardiovascular herbs, i.e. Panax, Ligusticum, Carthamus, and Pueraria plants, are traditionally and globally used in the prevention and treatment of various cardiovascular diseases. Modern phytochemical studies have found many medicinal compounds from these plants, and their unique pharmacological activities are being revealed. However, there are few reviews that systematically summarize the current trends of Drug Metabolism/Pharmacokinetic (DMPK) investigations of cardiovascular herbs. METHODS: Here, the latest understanding, as well as the knowledge gaps of the DMPK issues in drug development and clinical usage of cardiovascular herbal compounds, was highlighted. RESULTS: The complicated herb-herb interactions of cardiovascular Traditional Chinese Medicine (TCM) herb pair/formula significantly impact the PK/pharmacodynamic performance of compounds thereof, which may inspire researchers to develop a novel herbal formula for the optimized outcome of different cardiovascular diseases. While the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME/T) of some compounds has been deciphered, DMPK studies should be extended to more cardiovascular compounds of different medicinal parts, species (including animals), and formulations, and could be streamlined by versatile omics platforms and computational analyses. CONCLUSION: In the context of systems pharmacology, the DMPK knowledge base is expected to translate bench findings to clinical applications, as well as foster cardiovascular drug discovery and development.

10.
Biomed Res Int ; 2019: 9783106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183380

RESUMO

Purpose: To evaluate the diagnostic performance of deep learning with a multichannel fusion three-dimensional convolutional neural network (MCF-3DCNN) in the differentiation of the pathologic grades of hepatocellular carcinoma (HCC) based on dynamic contrast-enhanced magnetic resonance images (DCE-MR images). Methods and Materials: Fifty-one histologically proven HCCs from 42 consecutive patients from January 2015 to September 2017 were included in this retrospective study. Pathologic examinations revealed nine well-differentiated (WD), 35 moderately differentiated (MD), and seven poorly differentiated (PD) HCCs. DCE-MR images with five phases were collected using a 3.0 Tesla MR scanner. The 4D-tensor representation was employed to organize the collected data in one temporal and three spatial dimensions by referring to the phases and 3D scanning slices of the DCE-MR images. A deep learning diagnosis model with MCF-3DCNN was proposed, and the structure of MCF-3DCNN was determined to approximate clinical diagnosis experience by taking into account the significance of the spatial and temporal information from DCE-MR images. Then, MCF-3DCNN was trained based on well-labeled samples of HCC lesions from real patient cases by experienced radiologists. The accuracy when differentiating the pathologic grades of HCC was calculated, and the performance of MCF-3DCNN in lesion diagnosis was assessed. Additionally, the areas under the receiver operating characteristic curves (AUC) for distinguishing WD, MD, and PD HCCs were calculated. Results: MCF-3DCNN achieved an average accuracy of 0.7396±0.0104 with regard to totally differentiating the pathologic grade of HCC. MCF-3DCNN also achieved the highest diagnostic performance for discriminating WD HCCs from others, with an average AUC, accuracy, sensitivity, and specificity of 0.96, 91.00%, 96.88%, and 89.62%, respectively. Conclusions: This study indicates that MCF-3DCNN can be a promising technology for evaluating the pathologic grade of HCC based on DCE-MR images.

11.
J Cell Physiol ; 234(10): 18544-18559, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30982985

RESUMO

Low retention of endothelial progenitor cells (EPCs) in the infarct area has been suggested to be responsible for the poor clinical efficacy of EPC therapy for myocardial infarction (MI). This study aimed to evaluate whether magnetized EPCs guided through an external magnetic field could augment the aggregation of EPCs in an ischemia area, thereby enhancing therapeutic efficacy. EPCs from male rats were isolated and labeled with silica-coated magnetic iron oxide nanoparticles to form magnetized EPCs. Then, the proliferation, migration, vascularization, and cytophenotypic markers of magnetized EPCs were analyzed. Afterward, the magnetized EPCs (1 × 106 ) were transplanted into a female rat model of MI via the tail vein at 7 days after MI with or without the guidance of an external magnet above the infarct area. Cardiac function, myocardial fibrosis, and the apoptosis of cardiomyocytes were observed at 4 weeks after treatment. In addition, EPC retention and the angiogenesis of ischemic myocardium were evaluated. Labeling with magnetic nanoparticles exhibited minimal influence to the biological functions of EPCs. The transplantation of magnetized EPCs guided by an external magnet significantly improved the cardiac function, decreased infarction size, and reduced myocardial apoptosis in MI rats. Moreover, enhanced aggregations of magnetized EPCs in the infarcted border zone were observed in rats with external magnet-guided transplantation, accompanied by the significantly increased density of microvessels and upregulated the expression of proangiogenic factors, when compared with non-external-magnet-guided rats. The magnetic field-guided transplantation of magnetized EPCs was associated with the enhanced aggregation of EPCs in the infarcted border zone, thereby improving the therapeutic efficacy of MI.

12.
Bosn J Basic Med Sci ; 19(3): 288-296, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30878034

RESUMO

Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired respiratory tract infections (RTIs). We aimed to investigate the prevalence of M. pneumoniae infection, antibiotic resistance and genetic diversity of M. pneumoniae isolates across multiple centers in Beijing, China. P1 protein was detected by Nested PCR to analyze the occurrence of M. pneumoniae in pediatric patients with RTI. M. pneumoniae isolates were cultured and analyzed by Nested-PCR to determine their genotypes. Broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of antibiotics. Out of 822 children with RTI admitted to 11 hospitals in Beijing, 341 (41.48%) were positive for M. pneumoniae by Nested PCR and 236 (69.21%) samples had mutations in 23S rRNA domain V. The highest proportion of M. pneumoniae positive samples was observed in school-age children (118/190; 62.11%) and in pediatric patients with pneumonia (220/389; 56.56%). Out of 341 M. pneumoniae positive samples, 99 (12.04%) isolates were successfully cultured and the MIC values were determined for 65 M. pneumoniae strains. Out of these, 57 (87.69%) strains were resistant to macrolides, and all 65 strains were sensitive to tetracyclines or quinolones. M. pneumoniae P1 type I and P1 type II strains were found in 57/65 (87.69%) and 8/65 (12.31%) of cultured isolates, respectively. Overall, we demonstrated a high prevalence of M. pneumoniae infection and high macrolide resistance of M. pneumoniae strains in Beijing. School-age children were more susceptible to M. pneumoniae, particularly the children with pneumonia. Thus, establishment of a systematic surveillance program to fully understand the epidemiology of M. pneumoniae is critical for the standardized use of antibiotics in China.

13.
Genes Genomics ; 41(7): 803-810, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30877641

RESUMO

BACKGROUND: Ischemia heart disease is one of the major causes of death worldwide which often associated with tissue infarction and limit the recovery of function. Multiple factors involved in the I/R-induced cardiomyocyte dysfunction which were consistent with a role of oxidative stress and altered endothelium-dependent responses. However, the pathogenic mechanisms in I/R injury remain unclear. MATERIALS AND METHODS: The H9C2 cells were in the ischaemia/reperfusion (I/R) condition. After I/R, the cells were transfected with or without adenovirus-urothelial carcinoma associated 1(Ad-UCA1). Then qRT-PCR analysis was performed to quantify mRNA expression of different treatment groups. Cell apoptosis rate was assessed using flow cytometry and ER stress biomarker expression were measured by immunoblotting. Intracellular and mitochondrial ROS generation were assayed by fluorescence microscope after staining with the DCFDA or MitoSOX. RESULTS: I/R conditions trigger lncRNAs UCA1 expression, cellular and mitochondria ROS production, resulting in cell apoptosis through the induction of oxidative and ER stress. Overexpression of UCA1 protects H9C2 cells from I/R-induced ER stress and cell apoptosis. Moreover, UCA1 might be a potential regulator in the protective effect of I/R­induced oxidative stress and mitochondria dysfunction. Subsequently, ER stress inhibitor attenuated the effect of siUCA1 induced injury in H9C2 cells. CONCLUSION: The expression of UCA1 against I/R induced oxidative stress and mitochondria dysfunction via suppression of endoplasmic reticulum stress. UCA1 might be a biomarker to improved diagnosis of I/R injury.

14.
Medicine (Baltimore) ; 98(12): e14941, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30896660

RESUMO

The aim of this study was to investigate the influence of vertebral bone mineral density (BMD) on total diffusion volume of bone cement in percutaneous vertebroplasty (PVP). This study was a retrospective review of prospectively collected data of consecutive patients with A1.2 thoracolumbar compression fractures treated by PVP. Vertebral BMD was measured before surgery and participants were divided into 3 groups according to World Health Organization diagnostic criteria for osteoporosis: Group A (normal BMD), Group B (reduced BMD), and Group C (osteoporosis). All vertebrae were injected with 3 mL of bone cement via the unilateral pedicle and scanned by computed tomography after surgery. Actual injection volume (bone cement only) and total diffusion volume (bone cement plus trabeculae and space) were calculated. Pain severity was determined by the visual analog scale before surgery and at both 1 day and 1 month after surgery. There were no significant differences in injection volume among the groups (P > .05), but the total dispersion volume was greater than injection volume in all groups (P < .05). Pairwise comparison showed a significant difference in total diffusion volume of bone cement between groups, with Group A having the largest volume and Group C the smallest volume. Pain was significantly reduced 1 day after surgery in each group compared with before surgery, but there were no significant between-group differences at 1 day or 1 month. Increasing vertebral BMD was positively correlated with increasing total diffusion volume. BMD does not significantly affect pain relief, despite producing a significantly lower distribution volume in osteoporotic patients.


Assuntos
Cimentos para Ossos/uso terapêutico , Densidade Óssea/fisiologia , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas por Compressão/epidemiologia , Humanos , Vértebras Lombares/fisiologia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Medição da Dor , Estudos Retrospectivos , Índice de Gravidade de Doença , Fraturas da Coluna Vertebral/epidemiologia , Vértebras Torácicas/fisiologia , Vértebras Torácicas/cirurgia
15.
Int J Nanomedicine ; 14: 1489-1501, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880960

RESUMO

Purpose: Antiangiogenic drugs usually have short-acting efficacy and poor treatment compliance. The purpose of this study was to determine whether mesoporous silica nanoparticles (MSNs) could be utilized as a nanodrug delivery system for improving antiangiogenic therapy. Materials and methods: MSN-encapsulated bevacizumab nanoparticles were prepared by the nanocasting strategy and characterized by Fourier transform infrared, transmission electron microscopy, and Brunauer-Emmett-Teller method. Encapsulation efficiency and drug loading efficiency of MSN-encapsulated bevacizumab nanoparticles were calculated. The pharmacokinetics, cytotoxicity, and tissue toxicity were evaluated in vitro and in vivo. The antiangiogenic effects of MSN-bevacizumab nanoparticles were evaluated in vitro and in vivo. Results: MSN encapsulation could prolong the residency of bevacizumab in vitreous/aqueous humor and maintain the long-lasting drug concentration. MSN-encapsulated bevacizumab nanoparticles did not show any obvious cytotoxicity and tissue toxicity. MSN-encapsulated bevacizumab nanoparticles were more effective than bevacizumab in suppressing vascular endothelial growth factor-induced endothelial cell proliferation, migration, and tube formation in vitro. MSN-encapsulated bevacizumab nanoparticles showed sustained inhibitory effects on corneal neovascularization and retinal neovascularization in vivo. Conclusion: This study provides a novel strategy of encapsulating bevacizumab to protect and deliver it, which could increase the time between administration and formulation shelf-life. MSN-encapsulated bevacizumab is a promising drug delivery alternative of antiangiogenic therapy.


Assuntos
Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Neovascularização da Córnea/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Dióxido de Silício/química , Inibidores da Angiogênese/administração & dosagem , Animais , Bevacizumab/administração & dosagem , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Porosidade
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 246-252, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738478

RESUMO

OBJECTIVE: To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations. METHODS: Thirty-one patients consulted in Children's Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively. RESULTS: All patients were male. The median onset age was 1 month (range, 0-83 months). Nine mutants were reported as novel mutations among 25 mutants detected in 31 patients, including c.1234_1235dupCC, c.1093-1097delG, c.28-30dupC, c.436G>T, c.273 + 10_273 + 11dupCC, c.995_996insG, c.1010T>A, c.332_333delCC and c.683C>T mutations. There were 25 cases of classic WAS which mutations included missense mutation, deletion mutation, insertion mutation, splicing mutation and nonsense mutation, 2 cases of X-linked thrombocytopenia (XLT) were induced by missense mutation, 1 case of intermittent X-linked thrombocytopenia (IXLT) was induced by splicing mutation, 2 cases of X-linked pancytopenia were induced by missense mutation. Intravenous immunoglobulin (IVIG) and glucocorticoid therapy in IXLT patient was effective, and remission could be sustained, platelets could be increased in the short-term in treated XLT patients, but only a small part of classic WAS patients(8.0%) showed transient response to it, the IVIG and glucocorticoid therapy did not improve the status of platelet in XLP patients. Immune laboratory examination showed that CD3+ was decreased in 60.0% patients, CD19+ was decreased in 12.0% patients, and CD56+CD16+ in 4 patients was decreased, accounting for 16.0%. Out of 24 patients, 22 patients were alive after treated with hematopoietic stem cell transplantation (HSCT), 4 patients who were not given HSCT died of brain bleeding and severe infection, 1 patient diagnosed as IXLT got remission and survived. CONCLUSION: WAS gene defect is an important basis for the diagnosis of WAS and related diseases. IVIG plus glucocorticoid therapy is less effective for fewer patients, the HSCT is an effective treatment for WAS.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X , Trombocitopenia , Proteína da Síndrome de Wiskott-Aldrich/genética , Humanos , Masculino , Mutação , Fenótipo , Estudos Retrospectivos
17.
Pediatr Res ; 85(5): 617-624, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30723311

RESUMO

BACKGROUND: BMI as a body weight indicator, may inadequately represent the biological effect of body fat on lipid profiles. This study aims to assess whether body fat indicators were superior to BMI for recognizing children with dyslipidemia. METHODS: A nationwide cross-sectional study involving 8944 pediatric participants aged 6-18 years. Measures of fat mass index (FMI), fat mass percentage (FMP), BMI, and four lipid profiles were obtained. RESULTS: Among boys, the standard multi-linear regression coefficients of FMI for TC, LDL-C, and TG were higher than those of BMI (P < 0.01), but not for HDL-C. Also, the prevalence ratios and area under curves (AUCs) of excess fat classified by FMI for specific abnormal lipid profiles (except for HDL-C) were greater than overweight classified by BMI. The AUCs for detecting children with abnormal TC, LDL-C, and TG of FMI-based excess fat were 3.9%, 5.6%, and 2.8% higher than those of BMI-based overweight, respectively, all P < 0.01. Among girls, the associations of BMI with lipid profiles were substantially similar to FMI. All these results were almost identical when FMP was used instead of FMI. CONCLUSIONS: DXA measured body fat performs better than BMI in identifying abnormal lipid profiles in boys but not in girls.

18.
Int J Gynecol Cancer ; 29(1): 28-34, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640680

RESUMO

OBJECTIVES: Since other genital infections enhance HIV susceptibility by inducing inflammation and evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of high-risk human papillomavirus (HPV) infections, we investigated the relationship between the composition of the vaginal microbiota and the risk of high-risk HPV infection. METHODS: The study included 151 healthy women (65 HPV-positive and 86 HPV-negative) aged 20-65 at enrollment. Total genome DNA from samples was extracted using the hexadecyltrimethylammonium bromide (CTAB) CTAB method. The vaginal microbiota composition was determined by sequencing barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. RESULTS: Of the 30 most abundant bacteria at the genus level, we found only six bacteria with a statistical difference between HPV-positive and HPV-negative women: Bacteroides, Acinetobacter, Faecalibacterium, Streptococcus, Finegoldia, and Moryella. Lactobacillus was the predominant genus and was detected in all women, but there was no significant difference between the two groups for L. iners, L. jensenii, and L. gasseri. Furthermore, we found 26 types of bacteria with a statistical difference at the species level between the two groups. Anaerobic bacteria such as Bacteroides plebeius, Acinetobacter lwoffii, and Prevotella buccae were found significantly more frequently in HPV-positive women, which is the most important finding of our study. CONCLUSION: Our findings suggest a possible role for the composition of the vaginal microbiota as a modifier of high-risk HPV infection, and specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with high-risk HPV infection. The exact molecular mechanism of the vaginal microbiota in the course of high-risk HPV infection and cervical neoplasia should be further explored. Future research should include intervention in the composition of the vaginal microbiota to reverse the course of high-risk HPV infection and the natural history of cervical neoplasia.

19.
Hum Mutat ; 40(4): 392-403, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30609140

RESUMO

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

20.
Food Chem ; 276: 675-679, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30409647

RESUMO

Lipophenols, esterified phenols with fatty acids, have attracted increasing attention because of their better protective effects in lipid-based food matrices from oxidation. However, little is known about their digestion. In this study, the digestive stability of resveratrol (RSV) esters with caprylic acid (RCAPs) in a model gastrointestinal digestion system was evaluated. The results demonstrated that RCAPs were relatively stable without hydrolysis in mouth and gastric phases. However, in the intestinal phase, pancreatic lipase rather than phospholipase A2 could hydrolyze monoester and diesters to free RSV. After 120 min of incubation at 37 °C, 53.68% of monoester and 11.36% of diesters were hydrolyzed. However, no hydrolysis of the triester was noticed. Obviously, the level of hydrolysis of RCAPs was negatively correlated with the degree of substitution. Therefore, it was speculated that RSV in fatty acid ester forms could partially be absorbed by intestinal lumen in the form of free RSV.


Assuntos
Caprilatos/química , Digestão , Resveratrol/química , Resveratrol/farmacocinética , Estabilidade de Medicamentos , Ésteres/química , Suco Gástrico/metabolismo , Trato Gastrointestinal/metabolismo , Hidrólise , Intestinos , Lipase/metabolismo , Boca/metabolismo , Oxirredução , Fosfolipases A2/metabolismo , Estômago
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