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1.
Mol Ther Methods Clin Dev ; 23: 633-643, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34901308

RESUMO

Our previous clinical study achieved complete remission (CR) rates of >90% following chimeric antigen receptor T cells targeting CD19 (CART19) treatment of refractory/relapsed B cell acute lymphoblastic leukemia (r/r B-ALL); however, the influence of the leukemia burden in peripheral blood (PB) blasts remains unclear. Here, we retrospectively analyzed 143 patients treated with CART19 (including 36 patients with PB blasts) to evaluate the effect of peripheral leukemia burden at the time of apheresis. One hundred seventeen patients with high disease burdens achieved 91.5% CR or incomplete count recovery CR and 86.3% minimal residual disease-negative CR, and 26 patients with low disease burdens obtained 96.2% MRD- CR. Collectively, 9 of 36 (25%) patients with PB blasts and 2 of 107 (1.87%) patients without PB blasts did not respond to CART19 therapy. The leukemia burden in PB negatively influenced ex vivo cell characteristics, including the transduction efficiency of CD3+ T cells and their fold expansion, and in vivo cell dynamics, including peak CART19 proportion and absolute count, fold expansion, and persistence duration. Further studies showed that these patients had higher programmed death-1 expression in CART19 products. Our data imply that PB blasts negatively affected CART19 production and the clinical efficacy of CART19 therapy in patients with r/r B-ALL.

2.
Angew Chem Int Ed Engl ; 60(48): 25404-25410, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550627

RESUMO

Heteroatom doped atomically dispersed Fe1 -NC catalysts have been found to show excellent activity toward oxygen reduction reaction (ORR). However, the origin of the enhanced activity is still controversial because the structure-function relationship governing the enhancement remains elusive. Herein, sulfur(S)-doped Fe1 -NC catalyst was obtained as a model, which displays a superior activity for ORR towards the traditional Fe-NC materials. 57 Fe Mössbauer spectroscopy and electron paramagnetic resonance spectroscopy revealed that incorporation of S in the second coordination sphere of Fe1 -NC can induce the transition of spin polarization configuration. Operando 57 Fe Mössbauer spectra definitively identified the low spin single-Fe3+ -atom of C-FeN4 -S moiety as the active site for ORR. Moreover, DFT calculations unveiled that lower spin state of the Fe center after the S doping promotes OH* desorption process. This work elucidates the underlying mechanisms towards S doping for enhancing ORR activity, and paves a way to investigate the function of broader heteroatom doped Fe1 -NC catalysts to offer a general guideline for spin-state-determined ORR.

3.
Int J Gen Med ; 14: 4517-4527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421310

RESUMO

Objective: This study aimed to reveal the potential function of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and emphasized its importance in brain low-grade glioma (LGG). Methods: We firstly explored the differential expression of MTHFD2 mRNA in LGG and normal tissues, followed by correlation analysis of MTHFD2 mRNA expression with patient's clinical characteristics. MTHFD2 protein expression in LGG and subcellular location were also evaluated. Then, survival analysis was performed to reveal the influence of MTHFD2 expression on the overall survival of patients, and Cox regression analysis was applied to predict the prognostic factor for overall survival of LGG. Finally, we performed functional analysis to reveal potential MTHFD2-associated pathways involved in LGG. Results: We found that MTHFD2 was highly expressed in LGG patients (P<0.05), and MTHFD2 expression was related to patient's age and IDH mutation status (all P<0.05). MTHFD2 protein was mainly localized to the mitochondria. Survival analysis showed that high expression of MTHFD2 desirably improved the prognosis of LGG patients (P<0.001), especially for those patients with age ≥45 years (P<0.05). But independent prognostic role of MTHFD2 in LGG was not observed. Pathway enrichment analysis indicated that MTHFD2 high expression significantly and positively participated in the pathway of one carbon pool by folate (all P<0.05). Conclusion: High expression of MTHFD2 was observed in LGG, which was favorable for the overall survival of LGG patients. Our results assumed that MTHFD2 high expression might play a pivotal role in LGG through positively regulating pathway of one carbon pool by folate.

4.
Small ; 17(36): e2102396, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34331412

RESUMO

Combining NO removal and NH3 synthesis, electrochemical NO reduction reaction (NORR) toward NH3 is considered as a novel and attractive approach. However, exploring suitable catalysts for NO-to-NH3 conversion is still a formidable task due to the lack of a feasible method. Herein, utilizing systematic first-principles calculations, a rational strategy for screening efficient single-atom catalysts (SACs) for NO-to-NH3 conversion is reported. This strategy runs the gamut of stability, NO adsorbability, NORR activity, and NH3 selectivity. Taking transition metal atom embedded in C2 N (TM-C2 N) as an example, its validity is demonstrated and Zr-C2 N is selected as a stable NO-adsorbable NORR catalyst with high NH3 selectivity. Therefore, this work has established a theoretical landscape for screening SACs toward NO-to-NH3 conversion, which will contribute to the application of SACs for NORR and other electrochemical reactions.


Assuntos
Elementos de Transição , Catálise , Óxido Nítrico
5.
J Phys Chem Lett ; 12(26): 6111-6118, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34170687

RESUMO

The highly active and selective carbon dioxide reduction reaction (CO2RR) can generate valuable products such as fuels and chemicals and reduce the emission of greenhouse gases. Single-atom catalysts (SACs) and dual-metal-sites catalysts (DMSCs) with high activity and selectivity are superior electrocatalysts for the CO2RR as they have higher active site utilization and lower cost than traditional noble metals. Herein, we explore a rational and creative density-functional-theory-based, machine-learning-accelerated (DFT-ML) method to investigate the CO2RR catalytic activity of hundreds of transition metal phthalocyanine (Pc) DMSCs. The gradient boosting regression (GBR) algorithm is verified to be the most desirable ML model and is used to construct catalytic activity prediction, with a root-mean-square error of only 0.08 eV. The results of ML prediction demonstrate Ag-MoPc as a promising CO2RR electrocatalyst with the limiting potential of only -0.33 V. The DFT-ML hybrid scheme accelerates the efficiency 6.87 times, while the prediction error is only 0.02 V, and it sheds light on the path to accelerate the rational design of efficient catalysts for energy conversion and conservation.

6.
BMC Cancer ; 21(1): 750, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187410

RESUMO

BACKGROUND: Tumor microenvironment (TME) critically contributed to the malignant progression of transformed cells and the chemical responses to chemotherapy reagents. Osteopontin (OPN) is a secretory onco-protein with several splicing isoforms, all of which were known to regulate tumor growth and able to alter cell-cell or cell-TME communication, however, the exact role and regulation of the OPN splicing isoforms was not well understood. METHODS: In this study, the effects of conditioned medium from the culture of OPN splicing isoforms overexpressing cells on cell functions were evaluated. The methods of nuclear calcium reporter assays and subcellular distribution of nuclear factor of activated T cells c2 (NFATc2) assays were used to investigate the molecular mechanism underlining the roles of OPN splicing isoforms. RESULTS: We found that the survival of NSCLC cells treated with cisplatin was increased by secretory OPNc in the condition medium, where reduction of apoptosis by OPNc was associated with the activation of cellular calcium signals and subsequent nuclear translocation of NFATc2. CONCLUSIONS: The results revealed a mechanism of OPN and downstream signal for tumor cells to survive in chemo-stressed TME, which emphasized the importance of secretory proteins in alternative splicing isoforms. Our study not only demonstrated the importance of OPN neutralization for anti-tumor effects, but also implied that modulation in calcium/NFATc2/ROS axis could be a novel approach for improving the long-term outcome of NSCLC treatment.


Assuntos
Cálcio/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Fatores de Transcrição NFATC/metabolismo , Osteopontina/genética , Isoformas de Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Transfecção , Microambiente Tumoral
7.
PLoS One ; 16(1): e0245626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481857

RESUMO

The dynamics of soil microbial communities are important for plant health and productivity. Soil microbial communities respond differently to fertilization. Organic water soluble fertilizer is an effective soil improver, which can effectively improve soil nutrient status and adjust soil pH value. However, little is known about the effects of water soluble fertilizers on soil microbial community, and the combined effects on soil nutrients and sugarcane productivity. Therefore, this study sought to assess the effects of water soluble fertilizer (1,050 kg/hm2 (WS1), 1,650 kg/hm2 (WS2)) and mineral fertilizer (1,500 kg/hm2 (CK)) on the soil microbial community, soil nutrients and crop yield of sugarcane. The results showed that compared with CK, the application of water soluble fertilizers (WS1 and WS2) alleviated soil acidity, increased the OM, DOC, and AK contents in the soil, and further improved agronomic parameters and sugarcane yield. Both WS1 and WS2 treatments significantly increased the species richness of microorganisms, especially the enrichment of beneficial symbiotic bacteria such as Acidobacteria and Planctomycetes, which are more conducive to the healthy growth of plants. Furthermore, we found that soil nutrient contents were associated with soil microbial enrichment. These results indicate that water soluble fertilizer affects the enrichment of microorganisms by improving the nutrient content of the soil, thereby affecting the growth and yield of sugarcane. These findings therefore suggest that the utilization of water soluble fertilizer is an effective agriculture approach to improve soil fertility.


Assuntos
Fertilizantes , Consórcios Microbianos , Raízes de Plantas , Rizosfera , Saccharum/microbiologia , Microbiologia do Solo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Saccharum/crescimento & desenvolvimento , Solubilidade , Água
8.
Heart ; 107(11): 881-887, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33148545

RESUMO

OBJECTIVE: This study aimed to estimate the global burden of atrial fibrillation/atrial flutter (AF/AFL). METHODS: We retrieved data from the Global Health Data Exchange query tool and estimated the age-standardised rates (ASRs) of prevalence, incidence and disability-adjusted life-years (DALYs) of AF/AFL, as well as the population attributable fraction (PAF) of risk factors contributing to DALYs. ASRs and sociodemographic index (SDI) were assessed using Pearson's correlation coefficients. RESULTS: In 2017, there were 37.6 million (95% uncertainty interval (UI) 32.5 to 42.6 million) individuals with AF/AFL globally. The prevalence rates increased with increased SDI values in most regions for all years. Men had a higher prevalence than women across all regions except for China. From 1990 to 2017, global prevalence rate decreased by 5.08% (95% UI -6.24% to -3.82%), with the largest decrease noted in the region with high SDI values. The global DALYs rate declined by 2.53% (95% UI -4.16 to -0.29). PAF of elevated systolic blood pressure for attributable DALYs accounted for the highest percentage, followed by high body mass index, alcohol use, high-sodium diet, smoking and lead exposure. CONCLUSIONS: Although the ASRs of prevalence, incidence and DALYs decreased from 1990 to 2017, the absolute number of patients with AF/AFL, annual number of new AF/AFL cases and DALYs lost due to AF/AFL increased. This indicates that the burden of AF/AFL is likely to remain high. Systematic surveillance is needed to better identify and manage AF/AFL so as to prevent its various risk factors and complications.

9.
Arch. bronconeumol. (Ed. impr.) ; 56(11): 697-703, nov. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-198925

RESUMO

INTRODUCTION: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility. MATERIAL AND METHODS: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk. RESULTS: We observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01-0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01-0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01-0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01-0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13-2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15-2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09-1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (Ars11207535Crs10889159Trs1155002 and Ars11207535Crs10889159Crs1155002) significantly decreased COPD risk. CONCLUSION: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population


INTRODUCCIÓN: El citocromo P450 (CYP) 2J2 es una enzima importante que controla la biosíntesis de los ácidos epoxieicosatrienoicos, y que podría desempeñar un papel en el desarrollo de la enfermedad pulmonar obstructiva crónica (EPOC). En este estudio, nuestro objetivo fue evaluar la influencia de los polimorfismos de CYP2J2 en la susceptibilidad a la EPOC. MATERIALES Y MÉTODOS: Se realizó un estudio de casos y controles que incluyó 313 casos de EPOC y 508 controles para investigar la asociación entre los polimorfismos de CYP2J2 y el riesgo de desarrollar EPOC. Se utilizó la plataforma Agena MassARRAY para genotipar los polimorfismos de CYP2J2. Se calcularon los odds ratio (OR) con unos intervalos de confianza (IC) del 95% para valorar la asociación entre los polimorfismos de CYP2J2 y el riesgo de la EPOC. RESULTADOS: Observamos que rs11207535 (homocigoto: OR: 0,08, IC 95%: 0,01-0,96; p = 0,047; recesivo: OR: 0,08; IC 95%: 0,01-0,94; p = 0,044), rs10889159 (homocigoto: OR: 0,08, IC 95%: 0,01-0,92; p = 0,043; recesivo: OR: 0,08, IC 95%: 0,01-0,90; p = 0,040) y rs1155002 (heterocigoto: OR: 1,63, IC 95%: 1,13-2,36; p = 0,009; dominante: OR: 1,64, IC 95%: 1,15-2,35; p = 0,006; aditivo: OR: 1,45, IC 95%: 1,09-1,92; p = 0,011) se asociaron significativamente con el riesgo de EPOC. Las pruebas alélicas mostraron que el alelo T de rs2280274 estaba relacionado con una disminución del riesgo de EPOC y el alelo T de rs1155002 se asoció con un mayor riesgo de EPOC. Los análisis estratificados indicaron que los efectos de los polimorfismos de CYP2J2 y el riesgo de EPOC dependían del sexo y del tabaquismo (p < 0,05). Además, 2 haplotipos (Ars11207535Crs10889159Trs1155002 y Ars11207535Crs10889159Crs1155002) reducían significativamente el riesgo de la EPOC. CONCLUSIÓN: El estudio sugirió que los polimorfismos de CYP2J2 se asociaban con la susceptibilidad a la EPOC en la población Han China


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/genética , Polimorfismo de Nucleotídeo Único , Sistema Enzimático do Citocromo P-450/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Fatores de Risco , Técnicas de Genotipagem , Fatores Sexuais , China , Grupo com Ancestrais do Continente Asiático/genética
10.
Cancer Cell Int ; 20: 452, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944000

RESUMO

Background: Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. It is recognized that a variety of secretory proteins released from the tumor cells exposed to chemo-drugs into the tumor microenvironment (TME) contributed to the cell-to-cell communication, and altered the drug sensitivity. One of these important factors is osteopontin (OPN), which exists in several functional forms from alternative splicing and post-translational processing. In colon cancer cells, increased total OPN expression was observed during the progression of tumors, however, the exact role and regulation of the OPN splicing isoforms was not well understood. Methods: We assayed precisely the abundance of major OPN splicing isoforms under 5-FU treatments in colon cancer cell lines with different sensitivities to 5-FU, and also evaluated the effects of the condition medium from OPN splicing isoforms overexpressed cells on cell functions. The methods of nuclear calcium reporter assays and ChIP (chromatin immunoprecipitation) assays were used to investigate the molecular mechanism underlining the production of OPN isoforms. Results: We discovered that OPNc was a most increased splicing isoform to a significant abundance following 5-FU treatment of colon cancer cells. OPNc as a secretory protein in the conditioned medium exerted a more potent effect to promote cell survival in 5-FU than other OPN isoforms. The kinetic response of nuclear calcium signals could be used to indicate an immediate effect of the conditioned medium containing OPNc and other isoforms. Methyl-CpG binding protein 2 (MeCP2) was identified to regulate the splicing of opn gene, where the phosphorylation of MeCP2 at S421 site, possibly by calmodulin dependent protein kinase II (CaMKII) was required. Conclusions: The results demonstrated that the production of OPNc was highly controlled under epigenetic regulations, where MeCP2 and the activation of nuclear calcium signaling were involved. It was also suggested that OPNc could transmit the stress signal of cells upon chemotherapy in TME and promoted the survival of adjacent colon cancer cells.

11.
Nanoscale ; 12(38): 20025-20032, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32996977

RESUMO

Harvesting solar energy for artificial photosynthesis is an emerging field in alternative energy research. In this work, the photocatalytic properties of InX(X = S, Se)/transition metal disulfide (MoS2 and WS2) van der Waals heterostructures have been investigated. The calculation results indicate that these heterostructures exhibit improved photocatalytic performance over that of isolated InX or transition metal disulfide monolayers. The studied heterostructures all have type-II band alignment with holes and electrons located at the TMD and InX side, respectively. This facilitates the spatial separation of photogenerated carriers and improves the photocatalytic efficiency. The carrier mobility of the designed heterostructures can be boosted compared with the isolated monolayers, thus enhancing the carrier transport properties. Moreover, the strain-tuned heterostructures can prominently manipulate the light-harvesting capability especially from the visible light to infrared light range. Among the studied heterostructures, InSe/MoS2 with the suitable band edge positions, excellent transport properties and strain tolerance, and the lowest overpotential for oxygen evolution, stands out as the most promising candidate for photocatalytic applications. This work opens an avenue for the design of highly efficient heterostructure photocatalysts for solar-to-energy applications.

12.
COPD ; 17(5): 595-600, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32757668

RESUMO

Chronic obstructive pulmonary disease (COPD) is a high incidence in the elderly and significantly affects the quality of life. CYP2C9 and CYP2C19 play an important role in tobacco-related diseases and inflammatory reactions. Thus, we aim to investigate the association between CYP2C9/CYP2C19 polymorphisms and the risk of COPD. In this study, a total of 821 subjects were recruited which include 313 COPD cases and 508 healthy controls. Seven SNPs of CYP2C9/CYP2C19 were selected for genotyping. The odds ratios (ORs) and 95% confidence interval (95% CI) were calculated using logistic regression analysis to evaluate the association between COPD risk and CYP2C9/CYP2C19 polymorphisms. Our study showed that A allele of rs9332220 in CYP2C9 was associated with reducing COPD risk (OR = 0.64, 95% CI = 0.43-0.94, p = 0.021). And rs111853758 G allele carrier could significantly decrease 0.35-fold COPD risk compared with T allele carrier (OR = 0.65, 95% CI = 0.45-0.96, p = 0.027). Furthermore, sex-based stratification analysis showed that rs9332220 and rs111853758 polymorphisms were associated with the risk of COPD in males. This is the first study to investigate the association between CYP2C9 and CYP2C19 genetic polymorphisms and COPD risk, which may give a new perspective on the prevention and diagnosis of COPD.


Assuntos
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Polimorfismo de Nucleotídeo Único/genética , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China , Feminino , Volume Expiratório Forçado , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
13.
Genomics ; 112(6): 4399-4405, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738269

RESUMO

PURPOSE: Genetic polymorphisms act a crucial role in chronic obstructive pulmonary disease (COPD) progression. This study aimed to investigate the correlation between CYP3A4 variants and COPD risk. METHODS: We carried out a case-control study of 821 individuals (313 patients and 508 healthy subjects) to identify the correlation of CYP3A4 SNPs with COPD risk in the Hainan Han population. The association was evaluated by Odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Our study showed that rs4646437 polymorphism was related to a significantly increased susceptibility to COPD (OR 1.45, 95% CI = 1.10-1.90, p = 0.008). Stratified analyses indicated that rs4646437 polymorphism was significantly related to an increased risk of COPD in males (OR 1.95, 95% CI = 1.19-3.20, p = 0.008). However, rs4646440 played a protective role in females (OR 0.54, 95% CI = 0.31-0.93, p = 0.024). Rs4646437 was found to significantly improve the risk of COPD in smokers (OR 1.67, 95% CI = 1.12-2.48, p = 0.011). While rs4646440 had a significantly lower susceptibility to COPD in non-smokers (OR 0.64, 95% CI = 0.45-0.90, p = 0.010). Haplotype analysis revealed that Ars4646440Trs35564277 haplotype of CYP3A4 was found to increase the risk of COPD in non-smokers (OR 1.71, 95% CI = 1.04-2.82, p = 0.034). CONCLUSION: Our result gives a new understanding of the association between CYP3A4 gene and COPD in the Hainan Han population.


Assuntos
Citocromo P-450 CYP3A/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/etnologia , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etnologia , Fumar
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(6): 602-607, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32571459

RESUMO

OBJECTIVE: To study the association between clinical phenotypes and genotypes in children with Becker muscular dystrophy (BMD)/Duchenne muscular dystrophy (DMD) so as to provide a theoretical basis for disease management, gene therapy, and prenatal diagnosis. METHODS: A retrospective analysis was performed for the clinical data and gene detection results of 52 children with BMD/DMD. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the DMD gene. The children with negative results of MLPA were further screened by exon chip capture combined with next-generation sequencing (NGS). The mothers of 20 probands were validated by sequencing. RESULTS: The pathogenic genes for BMD/DMD were detected in 50 children by MLPA and NGS, with a detection rate of 96%. Among the 52 children, 36 (69%) had gene deletion, 7 (13%) had duplication, and 7 (13%) had micromutation. Among the 43 children with deletion/duplication, 32 had DMD and 11 had BMD; 37 children (86%) met the reading frame rule, among whom 27 (96%) had DMD and 10 (67%) had BMD. All 7 children with micromutation had DMD. CONCLUSIONS: The reading frame rule has an extremely high predictive value for DMD but a limited predictive value for BMD.


Assuntos
Distrofia Muscular de Duchenne , Criança , Distrofina , Feminino , Deleção de Genes , Genótipo , Humanos , Reação em Cadeia da Polimerase Multiplex , Mutação , Fenótipo , Gravidez , Estudos Retrospectivos
15.
Respir Res ; 21(1): 86, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295578

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disease. Cytochrome P450 family 4 subfamily F member 2 (CYP4F2) belongs to cytochrome P450 superfamily of enzymes responsible for metabolism, its single nucleotide polymorphisms (SNPs) were reported to be involved in metabolism in the development of many diseases. The study aimed to assess the relation between CYP4F2 SNPs and COPD risk in the Hainan Han population. METHOD: We genotyped five SNPs in CYP4F2 in 313 cases and 508 controls by Agena MassARRAY assay. The association between CYP4F2 SNPs and COPD risk were assessed by χ2 test and genetic models. Besides, logistic regression analysis was introduced into the calculation for odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Allele model analysis indicated that rs3093203 A was significantly correlated with an increased risk of COPD. Also, rs3093193 G and rs3093110 G were associated with a reduced COPD risk. In the genetic models, we found that rs3093203 was related to an increased COPD risk, while rs3093193 and rs3093110 were related to a reduced risk of COPD. After gender stratification, rs3093203, rs3093193 and rs3093110 showed the association with COPD risk in males. With smoking stratification, rs3093144 was significantly associated with an increased risk of COPD in smokers. CYP4F2 SNPs were significantly associated with COPD risk. CONCLUSIONS: Our findings illustrated potential associations between CYP4F2 polymorphisms and COPD risk. However, large-scale and well-designed studies are needed to determine conclusively the association between the CYP4F2 SNPs and COPD risk.


Assuntos
/genética , Família 4 do Citocromo P450/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Vigilância da População , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Distribuição Aleatória
16.
Arch Bronconeumol (Engl Ed) ; 56(11): 697-703, 2020 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32224017

RESUMO

INTRODUCTION: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility. MATERIAL AND METHODS: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk. RESULTS: We observed rs11207535 (homozygote: OR=0.08, 95%CI=0.01-0.96, p=0.047; recessive: OR=0.08, 95%CI=0.01-0.94, p=0.044), rs10889159 (homozygote: OR=0.08, 95%CI=0.01-0.92, p=0.043; recessive: OR=0.08, 95%CI=0.01-0.90, p=0.040) and rs1155002 (heterozygote: OR=1.63, 95%CI=1.13-2.36, p=0.009; dominant: OR=1.64, 95%CI=1.15-2.35, p=0.006; additive: OR=1.45, 95%CI=1.09-1.92, p=0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p<0.05). Additionally, two haplotypes (Ars11207535Crs10889159Trs1155002 and Ars11207535Crs10889159Crs1155002) significantly decreased COPD risk. CONCLUSION: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.


Assuntos
Predisposição Genética para Doença , Doença Pulmonar Obstrutiva Crônica , Estudos de Casos e Controles , China , Sistema Enzimático do Citocromo P-450/genética , Humanos , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética
17.
Bioelectrochemistry ; 134: 107532, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32305864

RESUMO

Parkinson's Disease (PD) is a neurodegenerative chronic disorder which destroys brain tissue and result in impaired movement. Early diagnosis of PD before the appearance of clinical symptom is vital for effective treatment. High levels of proinflammatory cytokines found in PD patient's brains, as natural inflammation response product, are potential biomarkers for PD detection in the early stage. Herein, we developed an in vivo electrochemical immunosensing device based on glassy carbon rod to simultaneously detect three proinflammatory cytokines (IL-1ß, IL-6 and TNF-α). The levels of IL-1ß, IL-6 and TNF-α secreted by N2a cells significantly increased within 24 h after lipopolysaccharide (LPS) stimulation. Under in vivo conditions, the concentrations of IL-1ß, IL-6 and TNF-α in PD model group achieved by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally, were significantly higher than those in the control mouse group. The concentrations of three cytokines in vivo/vitro detected by this immunosensing device was comparable to that obtained by ELISA. Furthermore, this deployable immunosensing device was proved to be highly sensitive with the limits of detection (LODs) of 5 pg mL-1 for each cytokine, specific and reliable, suggesting its potential to be a universal immunosensing platform for early identification and diagnosis of PD in vivo in the future.


Assuntos
Técnicas Biossensoriais/instrumentação , Citocinas/metabolismo , Imunoensaio/instrumentação , Doença de Parkinson/metabolismo , Animais , Carbono/química , Modelos Animais de Doenças , Eletroquímica , Vidro/química , Limite de Detecção , Masculino , Camundongos , Fatores de Tempo
18.
Curr Med Sci ; 40(2): 372-379, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337699

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) is a major opportunistic pathogen in hospital-acquired infections. Thus, early diagnosis is the best strategy for fighting against these infections. In this report, we incorporated multiple cross displacement amplification (MCDA) combined with the malachite green (MG) for rapid, sensitive, specific and visual detection of P. aeruginosa by targeting the oprl gene. The MCDA-MG assay was conducted at 67°C for only 40 min during the amplification stage, and then products were directly detected by using colorimetric indicators (MG), eliminating the use of an electrophoresis instrument or amplicon analysis equipment. The entire process, including specimen processing (35 min), amplification (40 min) and detection (5 min), can be finished within 80 min. All 30 non-P. aeruginosa strains tested negative, indicating the high specificity of the MCDA primers. The analytical sensitivity of the MCDA-MG assay was 100 fg of genomic templates per reaction in pure culture, which was in complete accordance with MCDA by gel electrophoresis and real-time turbidity. The assay was also successfully applied to detecting P. aeruginosa in stool samples. Therefore, the rapidity, simplicity, and nearly equipment-free platform of the MCDA-MG technique make it possible for clinical diagnosis, and more.


Assuntos
Proteínas de Bactérias/genética , Infecção Hospitalar/microbiologia , Diarreia/microbiologia , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Colorimetria , Eletroforese , Fezes/microbiologia , Humanos , Reação em Cadeia da Polimerase , Pseudomonas aeruginosa/genética , Corantes de Rosanilina/química , Sensibilidade e Especificidade , Temperatura
19.
MethodsX ; 7: 100773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32140438

RESUMO

A compact beam-position monitor was constructed using a linear contact image sensor attached to a plastic scintillator and tested using a 230 MeV proton beam. The results indicate that the beam position can be obtained in real-time, and the beam position with a precision of up to 0.03 mm. The compactness and high precision of the device hold considerable potential for it to be used as a beam-position monitor and offline, daily quality assurance monitor in hadron therapy. •The method can provide a high precision and high resolution beam position for flash irradiation in particle therapy in real-time.•The method using contact image sensor with scintillator does not require a long focal length for camera and it is free of image distortion.•The method can be integrated into medical particle accelerator for feedback control and daily quality assurance.

20.
Theranostics ; 10(5): 2029-2046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089734

RESUMO

Metabolic syndrome (MTS) is a cluster of concurrent metabolic abnormal conditions. MTS and its component metabolic diseases are heterogeneous and closely related, making their relationships complicated, thus hindering precision treatment. Methods: We collected seven groups of samples (group a: healthy individuals; group b: obesity; group c: MTS; group d: hyperglycemia, group e: hypertension, group f: hyperlipidemia; group g: type II diabetes, n=7 for each group). We examined the molecular characteristics of each sample by metabolomic, proteomic and peptidomic profiling analysis. The differential molecules (including metabolites, proteins and peptides) between each disease group and the healthy group were recognized by statistical analyses. Furthermore, a two-step clustering workflow which combines multi-omics and clinical information was used to redefine molecularly and clinically differential groups. Meanwhile, molecular, clinical, network and pathway based analyses were used to identify the group-specific biological features. Results: Both shared and disease-specific molecular profiles among the six types of diseases were identified. Meanwhile, the patients were stratified into three distinct groups which were different from original disease definitions but presented significant differences in glucose and lipid metabolism (Group 1: relatively favorable metabolic conditions; Group 2: severe dyslipidemia; Group 3: dysregulated insulin and glucose). Group specific biological signatures were also systematically described. The dyslipidemia group showed higher levels in multiple lipid metabolites like phosphatidylserine and phosphatidylcholine, and showed significant up-regulations in lipid and amino acid metabolism pathways. The glucose dysregulated group showed higher levels in many polypeptides from proteins contributing to immune response. The another group, with better glucose/lipid metabolism ability, showed higher levels in lipid regulating enzymes like the lecithin cholesterol acyltransferase and proteins involved in complement and coagulation cascades. Conclusions: This multi-omics based study provides a general view of the complex relationships and an alternative classification for various metabolic diseases where the cross-talk or compensatory mechanism between the immune and metabolism systems plays a critical role.


Assuntos
Doenças Metabólicas/imunologia , Doenças Metabólicas/metabolismo , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Glucose/metabolismo , Humanos , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperlipidemias/sangue , Hiperlipidemias/metabolismo , Hipertensão/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos , Masculino , Doenças Metabólicas/classificação , Síndrome Metabólica/classificação , Metabolômica/métodos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Peptidomiméticos , Fosfatidilcolinas/metabolismo , Fosfatidilserinas/metabolismo , Proteômica/métodos , Regulação para Cima
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