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1.
Food Chem ; 307: 125546, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639580

RESUMO

Zearalenone (ZEN) is one of the most widely distributed harmful mycotoxins produced by Fusarium species, especially deposited in corn oil. In this study, we systematically tracked the changes of ZEN in the refining of corn oil, and especially during neutralization process. An alkali neutralization process could remove certain amounts of ZEN that was much more than that of others refining steps. In a mimicking condition, ZEN contents decreased continuously and significantly with increasing neutralization temperature. However, when returned to neutral, recoverable ZEN decreased with increasing temperature, which confirmed more degradation of ZEN at high temperature. HPLC-Q/TOF MS and NMR evidence showed that non-reversible hydrolyzate followed decarboxylation was observed in a high-temperature alkali neutralization condition. The results may serve as the scientific basis for the elimination of zearalenone in refined vegetable oils, and provide clues to understanding the oil-safety aspects of elimination of zearalenone.

2.
Sci China Life Sci ; 62(11): 1420-1458, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31686320

RESUMO

Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.

3.
Am J Hum Genet ; 105(4): 803-812, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564438

RESUMO

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.

4.
J Agric Food Chem ; 67(39): 10904-10912, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31508953

RESUMO

High-order multiple emulsions are of great interest in both fundamental research and industrial applications as vehicles for their encapsulation capability of actives. In this work, we report a hierarchically multicompartmental highly stable triple emulsion by emulsifying and assembling of natural Quillaja saponin. Water-in-oil-in-(oil-in-water) (W2/O2/(O1/W1)) triple emulsion indicates that the compartmented system consisted of surfaced saponin-coated nanodroplets (SNDs) and dispersed oil globules, which in turn contained smaller aqueous droplets. The effects of formulation parameters, including lipophilic emulsifier content, oil fraction, and SND concentration, on the formation of multiple emulsions were systematically investigated. The assembly into fibrillar network of SNDs at the outer oil-water interface effectively protected the triple emulsion droplets against flocculation and coalescence, and strongly prevented the osmotic-driven water diffusion between the internal water droplets and the external water phase, thus contributing to superior stability during 180 days storage. All of these characteristics make the multicompartmentalized emulsions suitable to co-encapsulate a hydrophilic bioactive (gardenia blue) and two hydrophobic bioactives (eapsanthin and curcumin) in a single emulsion droplet hierarchically for the segregation and protection of multiple cargos. This approach offers a promising route toward accessing the next generation of functional deliveries and encapsulation strategies.


Assuntos
Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Extratos Vegetais/química , Quillaja/química , Saponinas/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Emulsificantes/química , Emulsões/química , Glucosídeos/química , Óleos/química , Tamanho da Partícula , Água/química
5.
World Neurosurg ; 131: e247-e254, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31349073

RESUMO

OBJECTIVE: To explore the performance of neurite orientation dispersion and density imaging (NODDI) in grading gliomas and to evaluate the cellular proliferation. METHODS: NODDI and diffusion-weighted imaging were performed on 79 patients with histopathologically proven gliomas. Parameter maps of intracellular volume fraction (ICVF), orientation dispersion index (ODI), and apparent diffusion coefficient (ADC) were calculated. Regions of interest were placed in the most solid part of the tumor. These metrics were normalized to the contralateral normal-appearing white matter and correlated with Ki-67 expression. RESULTS: ICVF and ODI increased as tumor grades increased, whereas ADC decreased with the increase of tumor grades. Significant differences in normalized ICVF and ODI were observed between low-grade gliomas and high-grade gliomas (ICVF: 0.208 ± 0.104 vs. 0.718 ± 0.234; ODI: 0.952 ± 0.428 vs. 1.767 ± 0.636, P < 0.001, respectively) and between grades II and III (ICVF: 0.208 ± 0.104 vs. 0.603 ± 0.253; ODI: 0.952 ± 0.428 vs. 1.762 ± 0.542, P < 0.001, respectively). Normalized ICVF was also significantly different between grades III and IV (0.603 ± 0.253 vs. 0.803 ± 0.182, P = 0.004). Ki-67 labeling index was positively correlated with normalized ICVF and ODI (r = 0.755 and 0.572, P < 0.001, respectively), and negatively correlated with normalized ADC (r = -0.709, P < 0.001). CONCLUSIONS: NODDI is a promising method in grading gliomas and predicting cellular proliferation. These results may be of great significance for the clinical diagnosis and treatment of gliomas.

6.
Food Funct ; 10(8): 4522-4532, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31355399

RESUMO

Delivery systems with multicompartmental structures that allow simultaneous delivery of several cargos are of great interest in both fundamental research and industrial applications. Here, we report a facile and easily scalable approach to fabricate multi-compartmentalized microdroplets for achieving programmed release of hydrophobic cargoes. Well-dispersed nanodroplets stabilized by natural Quillaja saponin served as an effective colloid stabilizer for fabricating microscale emulsion droplets with multicompartment architectures comprising many nanoscale droplets as a shell and single microscale core. Control of the number of nanodroplets allows accurate manipulation of the interface permeability for flexible and controllable release of volatile compounds (e.g., 2,3-butanedione, cis-3-hexen-1-ol, ethyl butyrate, d-limonene). More interestingly, the multicompartment microdroplets exhibited a higher flexibility for programmed release of different volatile compounds, as well as curcumin, during in vitro digestion by introducing cargos into the shell subcompartments or core microcompartment. The promising results highlight the power of this multi-compartmentalized system toward accessing a powerful platform for functional cargo delivery strategies.

7.
Proc Natl Acad Sci U S A ; 116(24): 11776-11785, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31123148

RESUMO

The cytoplasmic coat protein complex-II (COPII) is evolutionarily conserved machinery that is essential for efficient trafficking of protein and lipid cargos. How the COPII machinery is regulated to meet the metabolic demand in response to alterations of the nutritional state remains largely unexplored, however. Here, we show that dynamic changes of COPII vesicle trafficking parallel the activation of transcription factor X-box binding protein 1 (XBP1s), a critical transcription factor in handling cellular endoplasmic reticulum (ER) stress in both live cells and mouse livers upon physiological fluctuations of nutrient availability. Using live-cell imaging approaches, we demonstrate that XBP1s is sufficient to promote COPII-dependent trafficking, mediating the nutrient stimulatory effects. Chromatin immunoprecipitation (ChIP) coupled with high-throughput DNA sequencing (ChIP-seq) and RNA-sequencing analyses reveal that nutritional signals induce dynamic XBP1s occupancy of promoters of COPII traffic-related genes, thereby driving the COPII-mediated trafficking process. Liver-specific disruption of the inositol-requiring enzyme 1α (IRE1α)-XBP1s signaling branch results in diminished COPII vesicle trafficking. Reactivation of XBP1s in mice lacking hepatic IRE1α restores COPII-mediated lipoprotein secretion and reverses the fatty liver and hypolipidemia phenotypes. Thus, our results demonstrate a previously unappreciated mechanism in the metabolic control of liver protein and lipid trafficking: The IRE1α-XBP1s axis functions as a nutrient-sensing regulatory nexus that integrates nutritional states and the COPII vesicle trafficking.

8.
Artif Cells Nanomed Biotechnol ; 47(1): 1833-1838, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31062617

RESUMO

This study aimed to explore the effect of cell division cycle protein 42 (CDC42) on inflammatory response and immune response in mice bearing inflammatory bowel disease (IBD). Trinitrobenzene sulfonic acid was injected into the colon of mice to establish IBD model. The mice were divided into four groups (n = 4): control, model, Ad5, and Ad5-CDC42. After establishing IBD model, mice which were treated with AD5 empty vector and AD5-CDC42 expression vector served as the Ad5 group and Ad5-CDC42 group, respectively. The mRNA and protein levels of interleukin 10 (IL-10), interferon-γ (IFN-γ), IL-4, and tumor necrosis factor-α (TNF-α) in the colon tissues were evaluated by RT-PCR and western blot, respectively. Their levels in the serum and colon tissues were examined by ELISA assay and immunohistochemical analysis, respectively. Their changes in the mRNA and protein levels were consistent and similar changes in the colon tissues and the serum were found among various groups. The levels of IL-10, IFN-γ, IL-4, and TNF-α were lowest in the control group. Their levels in the model group and the Ad5 group were similar (p > .05) and significantly higher than those in the control group (p < .05). In comparison with the model group and the Ad5 group, their levels were significantly reduced in the Ad5-CDC42 group (p < .05). In conclusion, the levels of inflammatory cytokines were elevated in the colon tissues and serum of IBD mice, which could be reduced by the CDC42 treatment. CDC42 regulated the inflammatory response and the innate immune response in IBD mice.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Animais , Colo/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
9.
EMBO J ; 38(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30858281

RESUMO

SREBPs are master regulators of lipid homeostasis and undergo sterol-regulated export from ER to Golgi apparatus for processing and activation via COPII-coated vesicles. While COPII recognizes SREBP through its escort protein SCAP, factor(s) specifically promoting SREBP/SCAP loading to the COPII machinery remains unknown. Here, we show that the ER/lipid droplet-associated protein Cideb selectively promotes the loading of SREBP/SCAP into COPII vesicles. Sterol deprivation releases SCAP from Insig and enhances ER export of SREBP/SCAP by inducing SCAP-Cideb interaction, thereby modulating sterol sensitivity. Moreover, Cideb binds to the guanine nucleotide exchange factor Sec12 to enrich SCAP/SREBP at ER exit sites, where assembling of COPII complex initiates. Loss of Cideb inhibits the cargo loading of SREBP/SCAP, reduces SREBP activation, and alleviates diet-induced hepatic steatosis. Our data point to a linchpin role of Cideb in regulated ER export of SREBP and lipid homeostasis.

10.
Food Funct ; 10(3): 1504-1512, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30785152

RESUMO

Due to the benefits involving brain development and cardiovascular health, algae oil which is rich in omega-3 fatty acids has become a popular dietary supplement in recent years. However, the incompatibility with water and poor oxidative stability limits its addition in foods and beverages. In this work, the formation and characterization of zein-based core-shell microcapsules with tunable shell thicknesses for the potential delivery of algae oil were reported. They were prepared based on the in situ precipitation of zein from the continuous phase onto the surface of oil droplets by self-assembly at a refrigerated temperature without any need for surfactants and cross-linkers. The shell thickness could be controlled by the ratio of algae oil to zein (O/Z), which was indicated by their characterization including static light scattering, confocal laser scanning microscopy and scanning electron microscopy. Evidence from the peroxide value and the hexanal level of the emulsions in a thermally accelerated storage test suggested that the oxidation degree of the loading algae oil was negatively correlated with the shell thickness of the capsules. Furthermore, the release profiles of vanillin, which was used as a model volatile lipophilic compound and masking agent for the off-flavor from algae oil, could be tuned by manipulating their shell thickness. This suggested that the all-natural edible core-shell microcapsule might further be used as a model system for the delivery of lipophilic compounds. They may further promote the sustainable use of underutilized water-insoluble proteins as functional biomaterials in functional foods and pharmaceutical applications.


Assuntos
Cápsulas/química , Óleos/administração & dosagem , Óleos/química , Zeína/química , Benzaldeídos/administração & dosagem , Benzaldeídos/química , Sistemas de Liberação de Medicamentos , Peroxidação de Lipídeos
11.
Food Chem ; 285: 414-422, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30797365

RESUMO

Buckwheat constitutes a good source of bioactive components. A dry fractionation of surface abrasion for polyphenol-enriched protein combined with hydrothermal treatment was evaluated as an alternative to conventional wet extraction from tartary buckwheat (Fagopyrum esculentum Moench). The protein contents and the total polyphenol contents of both free and bound polyphenol gradually decreased in the order from the outer to the inner fractions. Polyphenol-enriched buckwheat protein flour was successfully enrichment with a maximum polyphenol content of 55 mg/g. Moreover, starch digestibility and polyphenols bioaccessibility of the buckwheat protein were increased with hydrothermal treatment time, while protein digestibility decreased slightly. Besides, most of the aroma compounds increased during the hydrothermal treatment. The assessment results demonstrate that the sustainability dry surface abrasion process in combination with hydrothermal treatment should be encouraged in processing functional protein fractions and improving both qualities of end use products and health benefits.


Assuntos
Fracionamento Químico/métodos , Fagopyrum/química , Manipulação de Alimentos/métodos , Proteínas de Plantas/química , Polifenóis/química , Proteínas na Dieta/química , Farinha , Manipulação de Alimentos/instrumentação , Alimentos Fortificados , Proteínas de Plantas/farmacocinética , Polifenóis/análise , Polifenóis/farmacocinética , Amido
12.
J Agric Food Chem ; 67(9): 2637-2646, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30721052

RESUMO

A new facile route was reported to use the natural triterpene Quillaja saponin (QS)-stabilized orange emulsions as a template for the development of flavor oil powders and oleogels achieved by the tunable oil fraction and drying mode. A fibrosis network interfacial film from self-assembly of QS at the oil-water interface possibility contributed to the fabrication of stable emulsion precursors and subsequent oil powder and oleogels by packing oil droplets in the network structure. An oil powder containing as high as 93 wt % orange oil was obtained by spray drying, showing excellent stability, flowability, and reconstitution ability. Upon the medium water removal rate of freeze drying, porous structured solid products followed by oleogels by a simple shearing can be formed. Upon oven drying, a translucent oleogel with high oil loading of 98.2 wt % was obtained from the high internal phase emulsion template. The resulting oleogels showed tunable rheological and texture properties, thixotropic recovery by modulating the oil fraction and water evaporation rate, and reversibility to reconstituted emulsions. Structuring liquid oil into solid materials by simply drying the continuous water from solely QS-based emulsions is very encouraging and provides new insights into various functional applications in the fields of foods, pharmaceuticals, cosmetics, and agriculture.


Assuntos
Emulsões/química , Óleos Vegetais/química , Quillaja/química , Saponinas/química , Triterpenos/química , Dessecação/métodos , Tecnologia de Alimentos/métodos , Compostos Orgânicos/química , Pós/química , Reologia
13.
J Sci Food Agric ; 99(6): 3176-3185, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30548612

RESUMO

BACKGROUND: During the last decade buckwheat was reported to have positive health effects. The present study investigated a high-polyphenol buckwheat protein (Fagopyrum esculentum Moench) prepared by enzyme-assisted processing, together with its physicochemical properties, in vitro digestibility, and antioxidant activity. RESULTS: Buckwheat protein prepared from the synergistic enzymatic action of α-amylase and amyloglucosidase (E-BWP) had much higher polyphenol content than buckwheat protein prepared by isoelectric precipitation (I-BWP) or salt extraction (S-BWP). Rutin degraded during the process, giving quercetin. The protein constituents and amino acid composition of E-BWP were very similar to those of native buckwheat and were able to meet the WHO/FAO requirements for both children and adults. During in vitro digestion, E-BWP showed anti-digestive behavior with a nitrogen release that was lower than that of I-BWP or S-BWP. The positive effect of the polyphenol content of E-BWP resulted in a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) content and greater reducing activity. CONCLUSION: Buckwheat protein with high polyphenol content was successfully developed by enzyme-assisted processing. It had a well-balanced amino acid profile, antidigestive behavior, and high antioxidant activities. The results suggest that enzyme-assisted processing is promising in the production of polyphenol-enriched cereal protein, contributing higher functionality with good nutritional and antioxidant properties. © 2018 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Fagopyrum/química , Fagopyrum/metabolismo , Glucana 1,4-alfa-Glucosidase/química , Proteínas de Plantas/química , Polifenóis/análise , alfa-Amilases/química , Antioxidantes/metabolismo , Biocatálise , Digestão , Manipulação de Alimentos , Humanos , Proteínas de Plantas/metabolismo , Polifenóis/metabolismo , Sementes/química , Sementes/metabolismo
14.
Elife ; 72018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30251625

RESUMO

PCSK9 is a secreted protein that regulates plasma cholesterol levels and cardiovascular disease risk. Prior studies suggested the presence of an ER cargo receptor that recruits PCSK9 into the secretory pathway, but its identity has remained elusive. Here, we apply a novel approach that combines proximity-dependent biotinylation and proteomics together with genome-scale CRISPR screening to identify SURF4, a homologue of the yeast cargo receptor Erv29p, as a primary mediator of PCSK9 secretion in HEK293T cells. The functional contribution of SURF4 to PCSK9 secretion was confirmed with multiple independent SURF4-targeting sgRNAs, clonal SURF4-deficient cell lines, and functional rescue with SURF4 cDNA. SURF4 was found to localize to the early secretory pathway where it physically interacts with PCSK9. Deletion of SURF4 resulted in ER accumulation and decreased extracellular secretion of PCSK9. These findings support a model in which SURF4 functions as an ER cargo receptor mediating the efficient cellular secretion of PCSK9.

15.
Proc Natl Acad Sci U S A ; 115(27): 7039-7044, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29915090

RESUMO

The mitochondrial trifunctional protein (TFP) catalyzes three reactions in the fatty acid ß-oxidation process. Mutations in the two TFP subunits cause mitochondrial trifunctional protein deficiency and acute fatty liver of pregnancy that can lead to death. Here we report a 4.2-Å cryo-electron microscopy α2ß2 tetrameric structure of the human TFP. The tetramer has a V-shaped architecture that displays a distinct assembly compared with the bacterial TFPs. A concave surface of the TFP tetramer interacts with the detergent molecules in the structure, suggesting that this region is involved in associating with the membrane. Deletion of a helical hairpin in TFPß decreases its binding to the liposomes in vitro and reduces its membrane targeting in cells. Our results provide the structural basis for TFP function and have important implications for fatty acid oxidation related diseases.


Assuntos
Microscopia Crioeletrônica , Proteína Mitocondrial Trifuncional/ultraestrutura , Humanos , Proteína Mitocondrial Trifuncional/metabolismo , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína
16.
Proc Natl Acad Sci U S A ; 115(30): 7819-7824, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29915037

RESUMO

Insulin increases glucose uptake into adipose tissue and muscle by increasing trafficking of the glucose transporter Glut4. In cultured adipocytes, the exocytosis of Glut4 relies on activation of the small G protein RalA by insulin, via inhibition of its GTPase activating complex RalGAP. Here, we evaluate the role of RalA in glucose uptake in vivo with specific chemical inhibitors and by generation of mice with adipocyte-specific knockout of RalGAPB. RalA was profoundly activated in brown adipose tissue after feeding, and its inhibition prevented Glut4 exocytosis. RalGAPB knockout mice with diet-induced obesity were protected from the development of metabolic disease due to increased glucose uptake into brown fat. Thus, RalA plays a crucial role in glucose transport in adipose tissue in vivo.


Assuntos
Tecido Adiposo Marrom/metabolismo , Glucose/metabolismo , Homeostase , Proteínas ral de Ligação ao GTP/metabolismo , Células 3T3-L1 , Tecido Adiposo Marrom/patologia , Animais , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Deleção de Genes , Glucose/genética , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Camundongos , Camundongos Knockout , Proteínas ral de Ligação ao GTP/genética
17.
Proc Natl Acad Sci U S A ; 115(26): E5896-E5905, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29891721

RESUMO

Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.


Assuntos
Carnitina O-Palmitoiltransferase/metabolismo , Fígado Gorduroso , Flavonoides/farmacologia , Fígado/enzimologia , Mitocôndrias Hepáticas/enzimologia , Obesidade , Proteômica , Regulação Alostérica/efeitos dos fármacos , Animais , Sítios de Ligação , Dieta/efeitos adversos , Ativação Enzimática/efeitos dos fármacos , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/enzimologia , Fígado Gorduroso/patologia , Fígado Gorduroso/prevenção & controle , Células HeLa , Humanos , Fígado/patologia , Camundongos , Mitocôndrias Hepáticas/patologia , Obesidade/induzido quimicamente , Obesidade/enzimologia , Obesidade/prevenção & controle
19.
Proc Natl Acad Sci U S A ; 115(14): E3155-E3162, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29555761

RESUMO

The flow of cargo vesicles along the secretory pathway requires concerted action among various regulators. The COPII complex, assembled by the activated SAR1 GTPases on the surface of the endoplasmic reticulum, orchestrates protein interactions to package cargos and generate transport vesicles en route to the Golgi. The dynamic nature of COPII, however, hinders analysis with conventional biochemical assays. Here we apply proximity-dependent biotinylation labeling to capture the dynamics of COPII transport in cells. When SAR1B was fused with a promiscuous biotin ligase, BirA*, the fusion protein SAR1B-BirA* biotinylates and thus enables the capture of COPII machinery and cargos in a GTP-dependent manner. Biochemical and pulse-chase imaging experiments demonstrate that the COPII coat undergoes a dynamic cycle of engagement-disengagement with the transmembrane cargo receptor LMAN1/ERGIC53. LMAN1 undergoes a process of concentrative sorting by the COPII coat, via a dimeric sorting code generated by oligomerization of the cargo receptor. Similar oligomerization events have been observed with other COPII sorting signals, suggesting that dimeric/multimeric sorting codes may serve as a general mechanism to generate selectivity of cargo sorting.


Assuntos
Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Lectinas de Ligação a Manose/química , Lectinas de Ligação a Manose/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Células HeLa , Humanos , Lectinas de Ligação a Manose/genética , Proteínas de Membrana/genética , Mutação , Multimerização Proteica , Transporte Proteico , Via Secretória
20.
World J Gastroenterol ; 24(10): 1134-1143, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29563757

RESUMO

AIM: To investigate 30-year treatment outcomes associated with Budd-Chiari syndrome (BCS) at a tertiary hospital in China. METHODS: A total of 256 patients diagnosed with primary BCS at our tertiary hospital between November 1983 and September 2013 were followed and retrospectively studied. Cumulative survival rates and cumulative mortality rates of major causes were calculated by Kaplan-Meier analysis, and the independent predictors of survival were identified using a Cox regression model. RESULTS: Thirty-four patients were untreated; however, 222 patients were treated by medicine, surgery, or interventional radiology. Forty-four patients were lost to follow-up; however, 212 patients were followed, 67 of whom died. The symptom remission rates of treated and untreated patients were 81.1% (107/132) and 46.2% (6/13), respectively (P = 0.009). The cumulative 1-, 5-, 10-, 20-, and 30-year survival rates of the treated patients were 93.5%, 81.6%, 75.2%, 64.7%, and 58.2%, respectively; however, the 1-, 5-, 10-, 20-, and 30-year survival rates of the untreated patients were 70.8%, 70.8%, 53.1%, 0%, and unavailable, respectively (P = 0.007). Independent predictors of survival for treated patients were gastroesophageal variceal bleeding (HR = 3.043, 95%CI: 1.363-6.791, P = 0.007) and restenosis (HR = 4.610, 95%CI: 1.916-11.091, P = 0.001). The cumulative 1-, 5-, 10-, 20-, and 30-year mortality rates for hepatocellular carcinoma were 0%, 2.6%, 3.5%, 8%, and 17.4%, respectively. CONCLUSION: Long-term survival is satisfactory for treated Chinese patients with BCS. Hepatocellular carcinoma is a chronic complication and should be monitored with long-term follow-up.


Assuntos
Síndrome de Budd-Chiari/mortalidade , Carcinoma Hepatocelular/mortalidade , Varizes Esofágicas e Gástricas/mortalidade , Hemorragia Gastrointestinal/mortalidade , Neoplasias Hepáticas/mortalidade , Adolescente , Adulto , Idoso , Síndrome de Budd-Chiari/complicações , Síndrome de Budd-Chiari/terapia , Carcinoma Hepatocelular/etiologia , Criança , China/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/mortalidade , Varizes Esofágicas e Gástricas/etiologia , Feminino , Seguimentos , Hemorragia Gastrointestinal/etiologia , Veias Hepáticas/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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