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1.
Sci Total Environ ; 699: 134397, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31677469

RESUMO

Children are vulnerable to air pollution-induced lung function deficits, and the prevalence of obesity has been increasing in children. To evaluate the joint effects of long-term PM1 (particulate matter with an aerodynamic diameter ≤ 1.0 µm) exposure and obesity on children's lung function, a cross-sectional sample of 6740 children (aged 7-14 years) was enrolled across seven northeastern Chinese cities from 2012 to 2013. Weight and lung function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF), were measured according to standardized protocols. Average PM1, PM2.5, PM10 and nitrogen dioxide (NO2) exposure levels were estimated using a spatiotemporal model, and sulphur dioxide (SO2) and ozone (O3) exposure were estimated using data from municipal air monitoring stations. Two-level logistic regression and general linear models were used to analyze the joint effects of body mass index (BMI) and air pollutants. The results showed that long-term air pollution exposure was associated with lung function impairment and there were significant interactions with BMI. Associations were stronger among obese and overweight than normal weight participants (the adjusted odds ratios (95% confidence intervals) for PM1 and lung function impairments in three increasing BMI categories were 1.50 (1.07-2.11) to 2.55 (1.59-4.07) for FVC < 85% predicted, 1.44 (1.03-2.01) to 2.51 (1.53-4.11) for FEV1 < 85% predicted, 1.34 (0.97-1.84) to 2.04 (1.24-3.35) for PEF < 75% predicted, and 1.34 (1.01-1.78) to 1.93 (1.26-2.95) for MMEF < 75% predicted). Consistent results were detected in linear regression models for PM1, PM2.5 and SO2 on FVC and FEV1 impairments (PInteraction < 0.05). These modification effects were stronger among females and older participants. These results can provide policy makers with more comprehensive information for to develop strategies for preventing air pollution induced children's lung function deficits among children.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31689201

RESUMO

he development of the next-generation sequencing (NGS) technologies has led to massive amounts of VCF (Variant Call Format) files, which have been the standard formats developed with 1000 Genomes Project. At the same time, with the widespread use of biomedical ontologies in the biomedical community, more and more applications have accepted the Web Ontology Language (OWL) as the dominant data format for the specifications of biomedical ontology descriptions, leading to the rapid growth of OWL-based biomedical ontology scale. In this paper, we seek to explore an effective method for the management of VCF-based genetic variants and OWL-based biological ontologies using the MongoDB database. Considering many current applications (such as the short genetic variations database dbSNP, etc.) are transitioning to the new design by using JSON (JavaScript Object Notation) to support future massive data expansion and interchanges. We firstly propose a series of rules for the mapping from VCF and OWL files to JSON files, and then present rule-based algorithms for transforming VCF-based genetic variants and OWL-based biological ontologies into JSON objects. On this basis, we introduce effective approaches of integrating the mapped JSON files in MongoDB. Finally, we complement this work with a set of experiments to show the performance of our proposed approaches. The source code of the proposed approaches could be freely available at https://github.com/lyotvincent/AJIA.

3.
Wei Sheng Yan Jiu ; 48(5): 751-756, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31601315

RESUMO

OBJECTIVE: To investigate the association between environmental tobacco smoke( ETS) and blood pressure in children. METHODS: A cross-sectional study was conducted to study the effects of ETS and children's blood pressure among 1623 children aged 5 to 17 years, who were selected randomly from 10 primary and secondary schools in Shenyang from 2012-2013, Liaoning Province. The basic information of children was collected through questionnaires, including demographic characteristics, living environment, history of disease and passive smoking status. We also measured the height, weight and blood pressure of these children. Multiple Logistic regression analyses were used to determine whether ETS was associated with the risk of hypertension after adjustment for potential confounders. RESULTS: Nearly half of the participants( 37%, n = 600) had current ETS exposures, and in for 34% of the children( n = 514), their current ETS exposure was from tobacco use by their father. The adjusted odds ratios( a OR) for hypertension and ETS exposure in utero were 1. 59( 95% CI 1. 02-2. 48) in males and 2. 88( 95% CI 1. 82-4. 56) in females. Current ETS exposure( a OR = 2. 22, 95% CI 1. 47-3. 34) and current ETS exposure from the child's father( a OR = 2. 20, 95% CI 1. 46-3. 31), in addition different intensity of ETS exposure during workdays and during days off were associated with a higher rate of hypertension only in females. CONCLUSION: Prenatal and postnatal ETS exposure was significantly associated with increased odds of hypertension in children, especially in females.


Assuntos
Hipertensão/epidemiologia , Exposição Materna/estatística & dados numéricos , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Razão de Chances , Gravidez , Fumar/epidemiologia , Inquéritos e Questionários
4.
Planta ; 250(6): 1897-1910, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31485773

RESUMO

MAIN CONCLUSION: A homologue of the ribosomal protein L22e, Rpf84, regulates root nodule symbiosis by mediating the infection process of rhizobia and preventing bacteroids from degradation in Robinia pseudoacacia. Ribosomal proteins (RPs) are known to have extraribosomal functions, including developmental regulation and stress responses; however, the effects of RPs on symbiotic nodulation of legumes are still unclear. Ribosomal protein 22 of the large 60S subunit (RPL22), a non-typical RP that is only found in eukaryotes, has been shown to function as a tumour suppressor in animals. Here, a homologue of RPL22, Rpf84, was identified from the leguminous tree R. pseudoacacia. Subcellular localization assays showed that Rpf84 was expressed in the cytoplasm and nucleus. Knockdown of Rpf84 by RNA interference (RNAi) technology impaired the infection process and nodule development. Compared with the control, root and stem length, dry weight and nodule number per plant were drastically decreased in Rpf84-RNAi plants. The numbers of root hair curlings, infection threads and nodule primordia were also significantly reduced. Ultrastructure analyses showed that Rpf84-RNAi nodules contained fewer infected cells with fewer bacteria. In particular, remarkable deformation of bacteroids and fusion of multiple symbiosomes occurred in infected cells. By contrast, overexpression of Rpf84 promoted nodulation, and the overexpression nodules maintained a larger infection/differentiation region and had more infected cells filled with bacteroids than the control at 45 days post inoculation, suggesting a retarded ageing process in nodules. These results indicate for the first time that RP regulates the symbiotic nodulation of legumes and that RPL22 may function in initiating the invasion of rhizobia and preventing bacteroids from degradation in R. pseudoacacia.

5.
Environ Int ; 133(Pt A): 105160, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518937

RESUMO

BACKGROUND: Greater levels of serum per- and polyfluoroalkyl substances (PFAS) are known to be associated with higher uric acid which itself leads to a number of chronic diseases. However, whether this association varies across PFAS isomers which recently have been found to be associated with human health remains unknown. OBJECTIVES: To address this research gap, we explored isomer-specific associations between serum PFAS and uric acid in Chinese adults. METHODS: We conducted a cross-sectional study of associations between serum PFAS isomer and serum uric acid in 1612 participants from the Isomer of C8 Health Project. We used multivariable linear and logistic regression models to analyze serum isomers of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and other PFASs as continuous and categorical predictors of uric acid, adjusted for confounders. The association was also stratified by kidney function stage based on estimated glomerular filtration rate (GF-1, GF-2, GF-3a, and GF-3b/4). RESULTS: We found positive associations between serum PFAS isomer concentrations and uric acid. Uric acid levels were greater for each log-unit increase in branched PFOA (ß = 0.30, 95% CI: 0.21, 0.40), linear PFOA (ß = 0.18, 95% CI: 0.09, 0.26), branched PFOS (ß = 0.09, 95% CI: 0.02, 0.17) and linear PFOS (ß = 0.06, 95% CI: -0.01, 0.14) concentration. The associations between PFAS and uric acid showed an inverted 'U' shaped pattern across kidney function stages. For example, uric acid level was greater with each log-unit increase in total-PFOA among GF-1 (ß = 0.21, 95% CI: 0.06, 0.37), this relationship was greater in GF-3a (ß = 0.49, 95% CI: 0.09, 0.89) and decreased in GF-3b/4 (ß = -0.22, 95% CI: -0.83, 0.39). We also found the odds of hyperuricemia increased linearly with increasing branched PFOA in quartiles (odds ratio = 2.67, 95% CI: 1.86, 3.85 at the highest quartile). CONCLUSION: We report novel results in which PFAS associations with uric acid varied according to isomer and adult kidney function. Besides, our findings are consistent with previous epidemiologic studies in finding a positive association between serum PFAS concentrations and serum uric acid, especially for PFOA. Our results indicate that more research is needed to more clearly assess the impact of PFAS isomers on human health, which will help to refine regulation policies for PFAS.

6.
Math Biosci Eng ; 16(4): 3195-3214, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31499609

RESUMO

The only rubella vaccine available in North America is the RA27/3 strain (isolated from the kidney of a rubella-infected fetus and attenuated) licensed in 1979, which substituted HPV77/DE5 strain vaccine due to concerns about waning immunity. The first dengue vaccine (Dengvaxia CYDTDV) was first registered in Mexico in December, 2015, which is a live recombinant tetravalent dengue vaccine. Rubella vaccine was applied since 1969, but tetravalent dengue vaccine is being used in large scale nowadays. In the past, based on unavailable information regarded to rubella vaccine, mathematical models were used to design vaccination schemes in order to avoid congenital rubella syndrome (CRS). Currently, knowing that vaccine does not result in CRS, rubella vaccination is modelled as usual childhood infection. This experience of updated biological knowledge that influenced mathematical modellings of rubella vaccination is taken into account to reflect about the tetravalent dengue vaccine. We also address a discussion about the security of vaccination strategies.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1208-1214, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418381

RESUMO

OBJECTIVE: To investigate the anti-apoptotic effect of Angelica polysaccharide (APS) on cryopreservated platelets and its mechanism. METHODS: The platelets were divided into 4 group: control group(4 ℃ stored platelets),APS group (APS-treated platelets stored at 4 ℃), LY294002 group (LY294002-treated platelets stored at 4 ℃) and LY294002+APS group(LY294002+APS treated platelets stored at 4 ℃ ). The expression of platelet membrane glycoprotein CD41 and CD61, as well as the platelet apoptotic rate, Caspase 3 expression and mitochondrial membrane potential (MMP) were detected by flow cytometry; the anti-apoptotic mechanism of APS by PI3K /AKT signaling pathway was analyzed by Western blot assay. RESULTS: The apoptosis rate of platelets in LY294002 group obviously increased, the activity of CD41 and CD61 expression gradually decreased along with the enhancement of LY294002 concentrations (r=-0.953); compared with control group, the apoptosis rate of platelets in LY294002 group was enhanced significantly(P<0.05),while the apoptosis rate of platelets in LY294002+APS group significantly was reduced(P<0.05) as compare with LY294002 group, which suggest that APS has an anti-apoptotic effect on the cryopreserved platelets. APS decreased the expression of Caspase-3 and inhibited the reduction of mitochondrial membrane potential induced by LY294002, moreover, APS could increase the activation of PI3K /AKT pathway in Plt. CONCLUSION: APS has an anti-apoptotic effect on the cryopreserved platelets through activating the PI3K /AKT pathway, decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.


Assuntos
Angelica , Apoptose , Plaquetas , Cromonas , Morfolinas , Fosfatidilinositol 3-Quinases , Polissacarídeos , Proteínas Proto-Oncogênicas c-akt
8.
Invest Ophthalmol Vis Sci ; 60(10): 3689-3695, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469896

RESUMO

Purpose: To examine the role of ocular axial length as an ocular parameter for the prevalence and severity of diabetic retinopathy (DR). Methods: The cross-sectional Kailuan Diabetic Retinopathy Study included patients with diabetes who participated in the community-based longitudinal Kailuan Study and who had undergone ocular fundus photography. The fundus photographs were graded using the Early Treatment of Diabetic Retinopathy Study criteria. Results: The study included 1096 patients with diabetes (mean age: 60.8 ± 9.4 years; axial length: 23.37 ± 0.92 mm). In binary regression analysis, a higher DR prevalence was associated with shorter axial length (P = 0.007; odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.70, 0.95) after adjusting for longer known duration of diabetes (P = 0.02; OR: 1.13; 95%CI: 1.02, 1.24) and higher fasting blood glucose concentration (P < 0.001; OR: 1.38; 95%CI: 1.26, 1.52). A more severe DR stage was associated (regression coefficient r: 0.46) with shorter ocular axial length (P = 0.047; standardized regression coefficient ß: -0.06) after adjusting for higher fasting blood glucose (P < 0.001; ß: 0.41) and longer known duration of diabetes (P = 0.045; ß: 0.07). Longer axial length was associated with a lower DR prevalence (P = 0.003; ß: -0.10) after adjusting for younger age (P < 0.001), male sex (P < 0.001), higher body mass index (P = 0.016), and lower fasting blood glucose concentration (P = 0.036). Conclusions: After adjusting for systemic risk factors, DR prevalence decreased by 19% (95%CI: 5, 30) for each millimeter increase in axial length. With longer axial length being a surrogate for axial myopia, the marked increase in myopia prevalence worldwide may lead to a relative decrease in the prevalence and incidence of DR in future.

9.
J Cell Mol Med ; 23(10): 7099-7104, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31338992

RESUMO

Pathogenic mutation of protein C (PROC) gene results into the deficiency of PROC activity. This study aimed to identify the pathogenic genetic variants and to explore the functional consequence in Chinese familial venous thrombosis (VTE). Whole exome sequencing was performed to identify the pathogenic variants of anticoagulant factors. Serum coagulation and anti-coagulation factors activity were assayed to evaluate the genetic association. Functional study of PROC antigen secretion deficiency was conducted in VTE subjects and in vitro cell lines. One rare pathogenic variant (p.Ala178Pro) was identified in the four VTE subjects but not in the normal subjects from the family. An inframeshift variant (rs199469469) was also identified in a paediatric subject of the pedigree. Further evaluation of serum PROC activity levels in p.Ala178Pro variants VTE carriers showed significantly lower PROC activity compared to non-carriers. Furthermore, in vitro study showed that the p.Ala178Pro mutant cells had a consistent reduction in concentration of PROC antigen. In conclusions, our study demonstrated the pathogenic variant (p.Ala178Pro) contributed to PROC type I activity deficiency, which may be due to decreased secretion of PROC.

10.
Database (Oxford) ; 20192019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31343683

RESUMO

Resource Description Framework (RDF) is widely used for representing biomedical data in practical applications. With the increases of RDF-based applications, there is an emerging requirement of novel architectures to provide effective supports for the future RDF data explosion. Inspired by the success of the new designs in National Center for Biotechnology Information dbSNP (The Single Nucleotide Polymorphism Database) for managing the increasing data volumes using JSON (JavaScript Object Notation), in this paper we present an effective mapping tool that allows data migrations from RDF to JSON for supporting future massive data explosions and releases. We firstly introduce a set of mapping rules, which transform an RDF format into the JSON format, and then present the corresponding transformation algorithm. On this basis, we develop an effective and user-friendly tool called RDF2JSON, which enables automating the process of RDF data extractions and the corresponding JSON data generations.

11.
Molecules ; 24(13)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277200

RESUMO

Integrating graphene with other nanomaterials has created a variety of graphene nanocomposites with extraordinary chemical, optical, mechanical, and electrical properties [...].

12.
J Sep Sci ; 42(19): 3067-3076, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31347249

RESUMO

Ligustrazine was the active ingredient of the traditional Chinese medicine Chuanxiong Rhizoma. However, the content of ligustrazine is very low. We proposed a hypothesis that ligustrazine was produced by the mutual effects between endophytic Bacillus subtilis and the Ligusticum chuanxiong Hort. This study aimed to explore whether the endophytic B. subtilis LB5 could make use of Chuanxiong Rhizoma fermentation matrix to produce ligustrazine and clarify the mechanisms of action preliminarily. Ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry analysis showed the content of ligustrazine in Chuanxiong Rhizoma was below the detection limit (0.1 ng/mL), while B. subtilis LB5 produced ligustrazine at the yield of 1.0268 mg/mL in the Chuanxiong Rhizoma-ammonium sulfate fermentation medium. In the fermented matrix, the reducing sugar had a significant reduction from 12.034 to 2.424 mg/mL, and rough protein content increased from 2.239 to 4.361 mg/mL. Acetoin, the biosynthetic precursor of ligustrazine, was generated in the Chuanxiong Rhizoma-Ammonium sulfate (151.2 mg/mL) fermentation medium. This result showed that the endophytic bacteria B. subtilis LB5 metabolized Chuanxiong Rhizoma via secreted protein to consume the sugar in Chuanxiong Rhizoma to produce a considerable amount of ligustrazine. Collectively, our preliminary research suggested that ligustrazine was the interaction product of endophyte, but not the secondary metabolite of Chuanxiong Rhizoma itself.

13.
Cell Death Dis ; 10(7): 474, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209201

RESUMO

Reproductive problem has been one of the top issues for women health worldwide in recent decades. As a typical female disease, primary ovarian insufficiency (POI) results in a loss of ovarian follicles and oocytes that thus destroys women fertility. However, due to the complex of POI etiology and rare resource of human POI oocytes, few biomarkers have been identified in clinics and no effective strategy could be applied to treat POI patients. In the search of possible association between DNA damage and POI by Smart-Seq2 and RT2 profiler PCR array, we find that BRCA2, a core DNA repair gene for homologous recombination shows significantly lower expression in two POI patient oocytes. In line with this, we generated oocyte-specific knockout mouse model driven by Gdf9-Cre. The Brca2-deficient mice are infertile because of the arrested follicle development and defective oocyte quality caused by the accumulation of DNA damage. Notably, ectopic expression of Brca2 in Brca2-deficient oocytes could partially restore the oocyte maturation and chromosome stability. Collectively, our data assign a definite deficiency to BRCA2 as a POI driver during follicle development and oocyte maturation, and provide a potential fertility treatment strategy for POI patients induced by BRCA2 deficiency.

14.
Value Health ; 22(6): 642-647, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31198180

RESUMO

OBJECTIVE: To explore payer feedback regarding awareness of new gene therapies, sustainability of current financing mechanisms, unique challenges by payer segment, and need and preference for new financial models. STUDY DESIGN: Qualitative interview with standardized interview guide. METHODS: Sixty-minute telephone interviews were conducted with financial decision makers from 15 US payers between August and September 2017. RESULTS: One-third of payers interviewed (n = 5) were newly aware and learning about new gene therapies, 40% (n = 6) described watchful waiting, whereas 26.7% (n = 4) were engaged in active management. New payment models-specifically, performance-based agreements and risk-pooling-were supported by 47% (n = 7) of payers, whereas the current payment model was supported by 53% (n = 8). Major challenges included uncertainty related to utilization, cost, and duration of cure. Payers cited regulation, plan turnover, and ability to track long-term outcomes as barriers to implementation of new models. CONCLUSIONS: Access to new gene therapies may be impacted by payer ability to absorb the cost of coverage. Variation exists in awareness of new gene therapies and level of incorporation of new costs into future plan coverage. The sustainability of current financing mechanisms varies by payer segment, profitability, and size; smaller plans and Medicaid are likely to be impacted first. Government reinsurance, commercial reinsurance, and stop-loss insurance backstop current reimbursement models, dampening the need for urgent action. The tipping point for action may be severe premium inflation in stop loss and reinsurance. Payers are open to innovative financing models that improve financial predictability and reward clinical performance.


Assuntos
Terapia Genética/normas , Acesso aos Serviços de Saúde/normas , Terapia Genética/métodos , Gastos em Saúde/normas , Gastos em Saúde/tendências , Humanos , Entrevistas como Assunto/métodos , Medicaid/organização & administração , Medicare/organização & administração , Pesquisa Qualitativa , Estados Unidos
15.
Chemosphere ; 234: 162-170, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31207421

RESUMO

In this study, both the carbon and nitrogen metabolisms of two heterotrophic nitrification bacteria were investigated under aerobic and anaerobic conditions at 2 °C. Similar catabolism and anabolism trends were observed for the two bacteria in stable experimental systems under aerobic and anaerobic conditions. Based on the nitrogen and carbon balance analysis and adenosine triphosphate (ATP) calculation, we proposed the following metabolic pathways: i) aerobic: except for microbial assimilation, the carbon and nitrogen sources were removed through respiration and nitrification, which provided energy for cell synthesis; and ii) anaerobic: the nitrification process almost stopped and most of the carbon sources decomposed into inorganic carbon, which dissolved in the medium. Based on our proposed metabolic pathways, we speculated that the nitrifying process almost stopped under anaerobic conditions and the nitrification bacteria would degrade more carbon contaminants to produce energy and maintain the cell growth. Furthermore, these bacteria may decompose the non-readily biodegradable carbon through anaerobic degradation. To verify these hypotheses, experiments with two types of synthetic wastewater were conducted: i) synthetic wastewater rich in carbon and poor in nitrogen, and higher carbon removal efficiencies of strain J and strain P (∼25%) were obtained under anaerobic conditions compared with aerobic conditions (∼19%); and ii) synthetic wastewater with recalcitrant carbon sources, and carbon removal efficiencies under anaerobic conditions were higher than those under aerobic conditions. The results of the synthetic wastewater experiments were consistent with the hypotheses and thus validated the metabolic pathways proposed for carbon and nitrogen.


Assuntos
Aerobiose , Anaerobiose , Carbono/metabolismo , Redes e Vias Metabólicas , Nitrogênio/metabolismo , Bactérias/metabolismo , Temperatura Baixa , Processos Heterotróficos , Nitrificação , Águas Residuárias/química
16.
Trends Pharmacol Sci ; 40(7): 447-448, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31122764

RESUMO

Recently, Costales and colleagues (J. Am. Chem. Soc. 2019;141:2960-2974) reported a bivalent small molecule inhibitor of primary miRNA (pri-miR)-515. Perturbation of pri-miR-515 results in the upregulation of HER2 protein levels, rendering HER2- breast cancer cells more sensitive to Herceptin treatment. This strategy represents a novel pharmacological approach to selectively modulating disease-relevant proteins in tumor cells.

17.
Cell Cycle ; 18(11): 1254-1267, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31111756

RESUMO

Mammalian oocyte meiosis is a special form of cell division that provides haploid gametes for fertilization. Unlike in mitosis, post-translational modifications (PTMs) are more crucial during meiosis because of the absence of de novo mRNA transcription. As a classic PTM, protein neddylation is a biological process that mediates protein degradation by modifying cullin proteins and activating the Cullin-Ring E3 ligases. This process plays important roles in various biological processes such as autophagy and tumorigenesis. However, the function of neddylation in germ cells is unknown. In this study, we observed that the inhibition of neddylation by its specific inhibitor MLN4924 significantly arrests mouse oocyte at the stage of metaphase during meiosis. The arrested oocytes display impaired spindles with over-activation of spindle assembly checkpoint (SAC). Accordingly, we identified early mitosis inhibitor 1 (Emi1), a key inhibitor of anaphase-promoting complex/cyclosome (APC/CFzr1), as a substrate of neddylation-mediated protein degradation. Thus, our study uncovered an unknown role of neddylation in female germ cells and suggests that proper neddylation is essential for oocyte maturation.

18.
Medicine (Baltimore) ; 98(18): e15432, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045806

RESUMO

INTRODUCTION: There are few studies focusing on Binocular hepatitis B related optic neuritis (HB-ON) and associated therapies are still limited. We present a case of HB-ON which has been cured with therapeutic plasma exchange (TPE). PATIENT CONCERNS: The patient was diagnosed as acute hepatitis B in hepatology and got a rapid loss of binocular visual acuity (2/100 in the right eye and no light perception in the left eye) after the onset. DIAGNOSIS: Hepatitis B related optic neuritis. INTERVENTIONS: Methylprednisolone and therapeutic plasma exchange. OUTCOMES: The treatment of high dose methylprednisolone was not curative. After 5 TPE sessions, the patient's best corrected visual acuity (BCVA) returned to 20/20 in the right eye and finger counting (FC)/40 cm in the left eye. One month later, the visual acuity increased to 5/100 in the left eye. CONCLUSION: This is the first case in which we used TPE to cure HB-ON. Also, it can demonstrate the relationship between HB-ON and immunopathogenesis. The case may provide an effective method for the treatment of hormone invalid and disabled ON in clinical practice.


Assuntos
Hepatite B/complicações , Neurite Óptica/complicações , Neurite Óptica/terapia , Plasmaferese/métodos , Doença Aguda , Adulto , Anti-Inflamatórios/uso terapêutico , Humanos , Masculino , Metilprednisolona/uso terapêutico , Acuidade Visual
19.
Biophys J ; 116(10): 1803-1814, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31076101

RESUMO

Tumor cells disseminate to distant organs mainly through blood circulation in which they experience considerable levels of fluid shear stress. However, the effects of hemodynamic shear stress on biophysical properties and functions of circulating tumor cells (CTCs) in suspension are not fully understood. In this study, we found that the majority of suspended breast tumor cells could be eliminated by fluid shear stress, whereas cancer stem cells held survival advantages over conventional cancer cells. Compared to untreated cells, tumor cells surviving shear stress exhibited unique biophysical properties: 1) cell adhesion was significantly retarded, 2) these cells exhibited elongated morphology and enhanced spreading and expressed genes related to epithelial-mesenchymal transition or hybrid phenotype, and 3) surviving tumor cells showed reduced F-actin assembly and stiffness. Importantly, inhibiting actomyosin activity promoted the survival of suspended tumor cells in fluid shear stress, whereas activating actomyosin suppressed cell survival, which might be explained by the up- and downregulation of the antiapoptosis genes. Soft surviving tumor cells held survival advantages in shear flow and higher resistance to chemotherapy. Inhibiting actomyosin activity in untreated cells enhanced chemoresistance, whereas activating actomyosin in surviving tumor cells suppressed this ability. These findings might be associated with the corresponding changes in the genes related to multidrug resistance. In summary, these data demonstrate that hemodynamic shear stress significantly influences biophysical properties and functions of suspended tumor cells. Our study unveils the regulatory roles of actomyosin in the survival and drug resistance of suspended tumor cells in hemodynamic shear flow, which suggest the importance of fluid shear stress and actomyosin activity in tumor metastasis. These findings may reveal a new, to our knowledge, mechanism by which CTCs are able to survive hemodynamic shear stress and chemotherapy and may offer a new potential strategy to target CTCs in shear flow and combat chemoresistance through actomyosin.

20.
Cell Mol Life Sci ; 76(11): 2217-2229, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30980108

RESUMO

As the female gamete, meiotic oocytes provide not only half of the genome but also almost all stores for fertilization and early embryonic development. Because de novo mRNA transcription is absent in oocyte meiosis, protein-level regulations, especially the ubiquitin proteasome system, are more crucial. As the largest family of ubiquitin E3 ligases, Skp1-Cullin-F-box complexes recognize their substrates via F-box proteins with substrate-selected specificity. However, the variety of F-box proteins and their unknown substrates hinder our understanding of their functions. In this report, we find that Fbxo30, a new member of F-box proteins, is enriched in mouse oocytes, and its expression level declines substantially after the metaphase of the first meiosis (MI). Notably, depletion of Fbxo30 causes significant chromosome compaction accompanied by chromosome segregation failure and arrest at the MI stage, and this arrest is not caused by over-activation of spindle assembly checkpoint. Using immunoprecipitation and mass spectrometric analysis, we identify stem-loop-binding protein (SLBP) as a novel substrate of Fbxo30. SLBP overexpression caused by Fbxo30 depletion results in a remarkable overload of histone H3 on chromosomes that excessively condenses chromosomes and inhibits chromosome segregation. Our finding uncovers an unidentified pathway-controlling chromosome segregation and cell progress.


Assuntos
Segregação de Cromossomos , Cromossomos de Mamíferos/metabolismo , Proteínas F-Box/genética , Histonas/genética , Meiose , Proteínas Nucleares/genética , Oócitos/metabolismo , Fatores de Poliadenilação e Clivagem de mRNA/genética , Animais , Cromossomos de Mamíferos/ultraestrutura , Proteínas F-Box/antagonistas & inibidores , Proteínas F-Box/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Proteínas Nucleares/metabolismo , Oócitos/ultraestrutura , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo
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