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1.
J Cell Sci ; 134(20)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34528675

RESUMO

ATP11C, a member of the P4-ATPase family, translocates phosphatidylserine and phosphatidylethanolamine at the plasma membrane. We previously revealed that its C-terminal splice variant ATP11C-b exhibits polarized localization in motile cell lines, such as MDA-MB-231 and Ba/F3. In the present study, we found that the C-terminal cytoplasmic region of ATP11C-b interacts specifically with ezrin. Notably, the LLxY motif in the ATP11C-b C-terminal region is crucial for its interaction with ezrin as well as its polarized localization on the plasma membrane. A constitutively active, C-terminal phosphomimetic mutant of ezrin was colocalized with ATP11C-b in polarized motile cells. ATP11C-b was partially mislocalized in cells depleted of ezrin alone, and exhibited greater mislocalization in cells simultaneously depleted of the family members ezrin, radixin and moesin (ERM), suggesting that ERM proteins, particularly ezrin, contribute to the polarized localization of ATP11C-b. Furthermore, Atp11c knockout resulted in C-terminally phosphorylated ERM protein mislocalization, which was restored by exogenous expression of ATP11C-b but not ATP11C-a. These observations together indicate that the polarized localizations of ATP11C-b and the active form of ezrin to the plasma membrane are interdependently stabilized.


Assuntos
Adenosina Trifosfatases , Polaridade Celular , Membrana Celular , Citoplasma , Proteínas do Citoesqueleto , Fosfoproteínas
2.
Plants (Basel) ; 10(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371612

RESUMO

Korean ginseng is one of the most valuable medicinal plants worldwide. However, our understanding of ginseng proteomics is largely limited due to difficulties in the extraction and resolution of ginseng proteins because of the presence of natural contaminants such as polysaccharides, phenols, and glycosides. Here, we compared four different protein extraction methods, namely, TCA/acetone, TCA/acetone-MeOH/chloroform, phenol-TCA/acetone, and phenol-MeOH/chloroform methods. The TCA/acetone-MeOH/chloroform method displayed the highest extraction efficiency, and thus it was used for the comparative proteome profiling of leaf, root, shoot, and fruit by a label-free quantitative proteomics approach. This approach led to the identification of 2604 significantly modulated proteins among four tissues. We could pinpoint differential pathways and proteins associated with ginsenoside biosynthesis, including the methylerythritol 4-phosphate (MEP) pathway, the mevalonate (MVA) pathway, UDP-glycosyltransferases (UGTs), and oxidoreductases (CYP450s). The current study reports an efficient and reproducible method for the isolation of proteins from a wide range of ginseng tissues and provides a detailed organ-based proteome map and a more comprehensive view of enzymatic alterations in ginsenoside biosynthesis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34199728

RESUMO

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.


Assuntos
Dieta Hiperlipídica , Dislipidemias , Animais , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Fígado , Masculino , Obesidade/etiologia , Obesidade/prevenção & controle , Ratos , Ratos Sprague-Dawley , Soja
4.
Medicine (Baltimore) ; 100(20): e24571, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011020

RESUMO

INTRODUCTION: Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients. METHODS: We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3. RESULTS: We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], -0.07 to 015; I2 = 0%; P = 0.48) and ferritin levels (MD, -0.42 ng/mL; 95% CI, -1.61 to 0.78; I2 = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25-1.08; I2 = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06-36.76; I2 = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35-0.80; I2 = 0%; P = 0.003). Serious adverse events were not reported in any group. CONCLUSION: FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity. TRIAL REGISTRATION: The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905).


Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado/administração & dosagem , Hematínicos/administração & dosagem , Maltose/análogos & derivados , Complicações Hematológicas na Gravidez/tratamento farmacológico , Administração Intravenosa , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/etiologia , Feminino , Compostos Férricos/efeitos adversos , Óxido de Ferro Sacarado/efeitos adversos , Ferritinas/sangue , Hematínicos/efeitos adversos , Hemoglobinas/análise , Humanos , Maltose/administração & dosagem , Maltose/efeitos adversos , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(43): e22739, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120774

RESUMO

OBJECTIVES: It was recently proposed that a costoclavicular (CC) approach can be used in ultrasound (US)-guided infraclavicular brachial plexus block (BPB). In this study, we hypothesized that triple injections in each of the 3 cords in the CC space would result in a greater spread in the 4 major terminal nerves of the brachial plexus than a single injection in the CC space without increasing the local anesthetic (LA) volume. METHODS: Sixty-eight patients who underwent upper extremity surgery randomly received either a single injection (SI group, n = 34) or a triple injection (TI group, n = 34) using the CC approach. Ten milliliters of 2% lidocaine, 10 mL of 0.75% ropivacaine, and 5 mL of normal saline were used for BPB in each group (total 25 mL). Sensory-motor blockade of the ipsilateral median, radial, ulnar, and musculocutaneous nerves was assessed by a blinded observer at 5 minutes intervals for 30 minutes immediately after LA administration. RESULTS: Thirty minutes after the block, the blockage rate of all 4 nerves was significantly higher in the TI group than in the SI group (52.9% in the SI group vs 85.3% in the TI group, P = .004). But there was no significant difference in the anesthesia grade between the 2 groups (P = .262). The performance time was similar in the 2 groups (3.0 ±â€Š0.9 minutes in the SI group vs 3.2 ±â€Š1.2 minutes in the TI group, respectively; P = .54). DISCUSSION: The TI of CC approach increased the consistency of US-guided infraclavicular BPB in terms of the rate of blocking all 4 nerves without increasing the procedure time despite administering the same volume of the LA.


Assuntos
Anestésicos Locais/administração & dosagem , Bloqueio do Plexo Braquial/métodos , Antebraço/cirurgia , Mãos/cirurgia , Lidocaína/administração & dosagem , Ropivacaina/administração & dosagem , Adulto , Clavícula , Feminino , Humanos , Injeções/métodos , Injeções/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento
6.
Tomography ; 6(3): 301-307, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32879900

RESUMO

Predicting biochemical recurrence of prostate cancer is imperative for initiating early treatment, which can improve the outcome of cancer treatment. However, because of inter- and intrareader variability in interpretation of F-18 fluciclovine positron emission tomography/computed tomography (PET/CT), it is difficult to reliably discern between necrotic tissue owing to radiation therapy and tumor tissue. Our goal is to develop a computational methodology using Haralick texture analysis that can be used as an adjunct tool to improve and standardize the interpretation of F-18 fluciclovine PET/CT to identify biochemical recurrence of prostate cancer. Four main textural features were chosen by variable selection procedure using least absolute shrinkage and selection operator logistic regression and bootstrapping, and then included as predictors in subsequent logistic ridge regression model for prediction (n = 28). Age at prostatectomy, prostate-specific antigen (PSA) level before the PET/CT imaging, and number of days between the prostate-specific antigen measurement and PET/CT imaging were also included in the prediction model. The overfitting-corrected area under the curve and Brier score of the proposed model were 0.94 (95% CI: 0.81, 1.00) and 0.12 (95% CI: 0.03, 0.23), respectively. Compared with a model with textural features (TI model) and that with only clinical information (CI model), the proposed model achieved 2% and 32% increase in AUC and 8% and 48% reduction in Brier score, respectively. Combining Haralick textural features based on the PET/CT imaging data with clinical information shows a high potential of enhanced prediction of the biochemical recurrence of prostate cancer.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Aminoácidos , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia
7.
Mol Biol Cell ; 31(19): 2115-2124, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32614659

RESUMO

Mammalian P4-ATPases specifically localize to the plasma membrane and the membranes of intracellular compartments. P4-ATPases contain 10 transmembrane domains, and their N- and C-terminal (NT and CT) regions face the cytoplasm. Among the ATP10 and ATP11 proteins of P4-ATPases, ATP10A, ATP10D, ATP11A, and ATP11C localize to the plasma membrane, while ATP10B and ATP11B localize to late endosomes and early/recycling endosomes, respectively. We previously showed that the NT region of ATP9B is critical for its localization to the Golgi apparatus, while the CT regions of ATP11C isoforms are critical for Ca2+-dependent endocytosis or polarized localization at the plasma membrane. Here, we conducted a comprehensive analysis of chimeric proteins and found that the NT region of ATP10 proteins and the CT region of ATP11 proteins are responsible for their specific subcellular localization. Importantly, the ATP10B NT and the ATP11B CT regions were found to harbor a trafficking and/or targeting signal that allows these P4-ATPases to localize to late endosomes and early/recycling endosomes, respectively. Moreover, dileucine residues in the NT region of ATP10B were required for its trafficking to endosomal compartments. These results suggest that the NT and CT sequences of P4-ATPases play a key role in their intracellular trafficking.


Assuntos
Membrana Celular/metabolismo , ATPases do Tipo-P/metabolismo , Domínios Proteicos , Sequência de Aminoácidos , Endossomos/metabolismo , Células HeLa , Humanos , ATPases do Tipo-P/química , Transporte Proteico
8.
Crit Rev Biochem Mol Biol ; 55(2): 166-178, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32408772

RESUMO

P4-ATPases, a subfamily of P-type ATPases, translocate cell membrane phospholipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet to generate and maintain membrane lipid asymmetry. Exposure of phosphatidylserine (PS) in the exoplasmic leaflet is well known to transduce critical signals for apoptotic cell clearance and platelet coagulation. PS exposure is also involved in many other biological processes, including myoblast and osteoclast fusion, and the immune response. Moreover, mounting evidence suggest that PS exposure is critical for neuronal regeneration and degeneration. In apoptotic cells, PS exposure is induced by irreversible activation of scramblases and inactivation of P4-ATPases. However, how PS is reversibly exposed and restored in viable cells during other biological processes remains poorly understood. In the present review, we discuss the physiological significance of reversible PS exposure in living cells, and the putative roles of flippases, floppases, and scramblases.


Assuntos
Membrana Celular/metabolismo , Citoplasma/metabolismo , ATPases do Tipo-P/metabolismo , Fosfatidilserinas/metabolismo , Animais , Apoptose/fisiologia , Sobrevivência Celular/fisiologia , Humanos , Bicamadas Lipídicas/metabolismo , ATPases do Tipo-P/classificação , Proteínas de Transferência de Fosfolipídeos/metabolismo , Ativação Plaquetária/fisiologia , Especificidade por Substrato
9.
Food Sci Nutr ; 8(3): 1562-1574, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32180965

RESUMO

The aim of this study was to compare whether gochujang products prepared using giant embryo rice koji (rice gochujang, RG) and wheat koji (wheat gochujang, WG) have anti-obesity effects on rats fed a high-fat diet (HFD), who served as a model for obesity. The nutritional composition of RG and WG including proximate constituents, amino acid and fatty acid compositions were investigated. Consequently, the secondary fermented metabolites were analyzed in RG and WG by ultrahigh-performance liquid chromatography and mass spectrometry. Rats were fed a HFD containing 10% RG powder (HFD-RG) or 10% WG powder (HFD-WG) for 8 weeks. Body weight gain, weights of liver, epididymal, retroperitoneal, perirenal, and total white fat pads, and levels of serum triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, and leptin were lower in all gochujang groups than in the HFD group. Furthermore, RG and WG treatment decreased the hepatic TG content and lipid accumulation and significantly reduced the size of epididymal adipocytes. These effects are probably mediated through inhibition of hepatic fatty acid synthase, acetyl CoA carboxylase, malic enzyme, and adipose tissue lipoprotein lipase activities. The anti-obesity effect was slightly greater in the HFD-RG group than in the HFD-WG group. This effect may be attributed to secondary metabolites, such as capsaicin, genistein, daidzein, soyasaponin, and lysophosphatidylcholines, contained in gochujang prepared using giant embryo rice or wheat koji.

10.
BMC Anesthesiol ; 20(1): 49, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32102676

RESUMO

BACKGROUND: Phase lag entropy (PLE) is a novel anesthetic depth indicator that uses four-channel electroencephalography (EEG) to measure the temporal pattern diversity in the phase relationship of frequency signals in the brain. The purpose of the study was to evaluate the anesthetic depth monitoring using PLE and to evaluate the correlation between PLE and bispectral index (BIS) values during propofol anesthesia. METHODS: In thirty-five adult patients undergoing elective surgery, anesthesia was induced with propofol using target-controlled infusion (the Schneider model). We recorded the PLE value, raw EEG, BIS value, and hemodynamic data when the target effect-site concentration (Ce) of propofol reached 2, 3, 4, 5, and 6 µg/ml before intubation and 6, 5, 4, 3, 2 µg/ml after intubation and injection of muscle relaxant. We analyzed whether PLE and raw EEG data from the PLE monitor reflected the anesthetic depth as the Ce of propofol changed, and whether PLE values were comparable to BIS values. RESULTS: PLE values were inversely correlated to changes in propofol Ce (propofol Ce from 0 to 6.0 µg/ml, r2 = - 0.83; propofol Ce from 6.0 to 2.0 µg/ml, r2 = - 0.46). In the spectral analysis of EEG acquired from the PLE monitor, the persistence spectrogram revealed a wide distribution of power at loss of consciousness (LOC) and recovery of consciousness (ROC), with a narrow distribution during unconsciousness. The power spectrogram showed the typical pattern seen in propofol anesthesia with slow alpha frequency band oscillation. The PLE value demonstrated a strong correlation with the BIS value during the change in propofol Ce from 0 to 6.0 µg/ml (r2 = 0.84). PLE and BIS values were similar at LOC (62.3 vs. 61.8) (P > 0.05), but PLE values were smaller than BIS values at ROC (64.4 vs 75.7) (P < 0.05). CONCLUSIONS: The PLE value is a useful anesthetic depth indicator, similar to the BIS value, during propofol anesthesia. Spectral analysis of EEG acquired from the PLE monitor demonstrated the typical patterns seen in propofol anesthesia. TRIAL REGISTRATION: This clinical trial was retrospectively registered at ClinicalTrials.gov at October 2017 (NCT03299621).


Assuntos
Anestésicos Intravenosos/farmacologia , Encéfalo/efeitos dos fármacos , Monitores de Consciência , Eletroencefalografia/instrumentação , Eletroencefalografia/métodos , Propofol/farmacologia , Adulto , Entropia , Feminino , Humanos , Masculino , Estudos Prospectivos , República da Coreia
11.
Transplant Proc ; 52(1): 219-226, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31889540

RESUMO

INTRODUCTION: The preoperative elevation of ammonia may be associated with postoperative neurologic complications. The aim of this study was to evaluate the effect of preoperative ammonia level on the incidence of delirium in patients after liver transplantation (LT). MATERIALS AND METHODS: Patients (n = 260) who received LT from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. The patients' demographic data, perioperative managements, and postoperative complications were assessed. Patients were divided into the following 2 groups: those who had a preoperative elevation (Group A, n = 158) and those with a normal range (Group C, n = 102). The cut-off value for a normal serum ammonia level in our hospital was defined as 32 µg/dL. RESULTS: After propensity score matching, there was no difference in the incidence of delirium between the groups (P = .784). Delirium occurred in 8 of 68 (11.76%) patients in Group A and 7 of 68 (10.29%) patients in Group C after LT. In addition, there was no difference in the incidence of delirium between the groups, even patients were categorized based on serum ammonia levels into 3 groups as follows: < 32 µg/dL (28/158 [17.72%]), 32 to 65 µg/dL (28/158 [17.72%]), and >65 µg/dL (28/158 [17.72%]) (P = .134). CONCLUSIONS: The preoperative serum ammonia level was not related with the incidence of postoperative delirium. The high elevation group, especially those with greater than 65 µg/dL of preoperative ammonia, was also not related with the incidence of delirium. However, our study is limited by its retrospective design, so future prospective studies are needed.


Assuntos
Amônia/sangue , Delírio/sangue , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/sangue , Idoso , Delírio/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Fatores de Risco
12.
Am J Reprod Immunol ; 83(4): e13222, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31958198

RESUMO

PROBLEM: Maternal obesity induces elevated saturated fatty acid palmitate levels in the blood and causes pregnancy complications such as gestational diabetes, preeclampsia, fetal growth abnormalities, and stillbirth. Sestrin2, a highly conserved stress-inducible protein, is involved in the cellular responses of various stress conditions and homeostatic regulation. However, the effects of Sestrin2 on trophoblast cells have not yet been investigated. Here, we investigated the role of Sestrin2 in palmitate-induced lipotoxicity and its underlying mechanisms in human first-trimester trophoblast cells (Sw.71). METHOD OF STUDY: Mouse placental tissues were obtained from low-fat diet-fed mice (n = 14) and high-fat diet-fed mice (n = 14) at gestation day 17.5. Sw.71 cells were treated with palmitate or bovine serum albumin as vehicle controls. The role of Sestrin2 in palmitate-induced lipotoxicity was examined by immunocytochemistry, immunoblot analysis, quantitative real-time PCR, and invasion assay. RESULTS: Expression of placental Sestrin2 was elevated in high-fat diet-fed dams compared to that of low-fat diet-fed dams. Prolonged treatment of Sw.71 cells with palmitate-induced endoplasmic reticulum (ER) stress-dependent expressions of Sestrin2 protein and mRNA, and the treatment also triggered apoptosis. Knockdown of Sestrin2 increased palmitate-mediated ER stress, inflammatory signaling, and apoptosis. Furthermore, Sestrin2 suppressed impaired trophoblast invasion caused by palmitate and attenuated palmitate-induced ER stress and inflammation via AMPK/mTORC1 pathways. CONCLUSION: Our study provides the relationship between Sestrin2, AMPK/mTORC1 pathway, and trophoblast function, suggesting that Sestrin2 may be a novel potential therapeutic target for the prevention of pregnancy complications.


Assuntos
Obesidade/metabolismo , Peroxidases/metabolismo , Complicações na Gravidez/metabolismo , Trofoblastos/metabolismo , Adenilato Quinase/metabolismo , Animais , Apoptose , Movimento Celular , Células Cultivadas , Estresse do Retículo Endoplasmático , Feminino , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Palmitatos/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Transdução de Sinais , Trofoblastos/patologia
13.
FEBS Lett ; 594(3): 412-423, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31571211

RESUMO

P4-ATPases belonging to the P-type ATPase superfamily mediate active transport of phospholipids across cellular membranes. Most P4-ATPases, except ATP9A and ATP9B proteins, form heteromeric complexes with CDC50 proteins, which are required for transport of P4-ATPases from the endoplasmic reticulum (ER) to their final destinations. P-type ATPases form autophosphorylated intermediates during the ATPase reaction cycle. However, the association of the catalytic cycle of P4-ATPases with their transport from the ER and their cellular localization has not been studied. Here, we show that transport of ATP9 and ATP11 proteins as well as that of ATP10A from the ER depends on the ATPase catalytic cycle, suggesting that conformational changes in P4-ATPases during the catalytic cycle are crucial for their transport from the ER.


Assuntos
Adenosina Trifosfatases/metabolismo , Retículo Endoplasmático/metabolismo , Adenosina Trifosfatases/química , Sequência de Aminoácidos , Biocatálise , Células HeLa , Humanos , Modelos Moleculares , Domínios Proteicos , Transporte Proteico
14.
J Asthma ; 57(12): 1316-1322, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340703

RESUMO

Objectives: The aim of this exploratory study was to assess the impact of caregiver health literacy (HL) on health care outcomes for their child with asthma.Methods: Caregiver dyads across two different healthcare delivery systems completed a battery of validated asthma outcome instruments, including the Newest Vital Sign™ as a measure of HL for the caregivers of children ages 7-18 y. Utilization history was obtained through the electronic medical record. Descriptive analysis with bivariate associations was conducted.Results: There was no direct relationship between HL and asthma outcomes in the 34 Hispanic and African American caregiver-child dyads. However, caregiver health literacy was significantly related to language (p = 0.02). African American English-speaking caregivers, seen in an urban emergency department, demonstrated adequate health literacy. Hispanic Spanish-speaking caregivers, seeking care in a mobile asthma van, showed limited health literacy. There was no significant association between caregivers' HL and routine asthma care visits when language and child age were controlled.Conclusions: Assessing patient factors can identify persons at risk who need additional support to negotiate the healthcare system when providing care for a child with asthma.


Assuntos
Asma/tratamento farmacológico , Cuidadores/estatística & dados numéricos , Letramento em Saúde/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Cuidadores/educação , Criança , Estudos Transversais , Escolaridade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Masculino , Pobreza/estatística & dados numéricos , Medição de Risco/métodos , Resultado do Tratamento
15.
J Cell Sci ; 132(17)2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31371488

RESUMO

ATP11C, a member of the P4-ATPase family, is a major phosphatidylserine (PS)-flippase located at the plasma membrane. ATP11C deficiency causes a defect in B-cell maturation, anemia and hyperbilirubinemia. Although there are several alternatively spliced variants derived from the ATP11C gene, the functional differences between them have not been considered. Here, we compared and characterized three C-terminal spliced forms (we designated as ATP11C-a, ATP11C-b and ATP11C-c), with respect to their expression patterns in cell types and tissues, and their subcellular localizations. We had previously shown that the C-terminus of ATP11C-a is critical for endocytosis upon PKC activation. Here, we found that ATP11C-b and ATP11C-c did not undergo endocytosis upon PKC activation. Importantly, we also found that ATP11C-b localized to a limited region of the plasma membrane in polarized cells, whereas ATP11C-a was distributed on the entire plasma membrane in both polarized and non-polarized cells. Moreover, we successfully identified LLXY residues within the ATP11C-b C-terminus as a critical motif for the polarized localization. These results suggest that the ATP11C-b regulates PS distribution in distinct regions of the plasma membrane in polarized cells.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Células 3T3-L1 , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Polaridade Celular/fisiologia , Citoplasma/metabolismo , Endocitose , Ativação Enzimática , Células HCT116 , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Camundongos , Isoformas de Proteínas , Proteína Quinase C/metabolismo , Células RAW 264.7
16.
Ann Allergy Asthma Immunol ; 123(2): 193-200, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31108180

RESUMO

BACKGROUND: Despite potential value of identification of allergic inflammation with fractional exhaled nitric oxide (FeNO) in managing asthma, randomized clinical trials have not consistently shown better outcomes compared with guideline management alone. OBJECTIVE: To assess the effectiveness of FeNO vs non-FeNO-based therapeutic algorithms in managing asthma, and the phenotypic profile associated with FeNO >35 ppb yet well controlled by guidelines, as a potential model to predict better FeNO-based algorithm outcomes. METHODS: This is a randomized controlled study (RCT) in 88 high-risk children with asthma 7 to 18 years of age across 352 visits over a 1-year period. Generalized estimating equations analysis assessed algorithm group differences in outcomes and characteristics associated with higher odds uncontrolled by FeNO alone in the treatment decision algorithm. RESULTS: The FeNO treatment algorithm did not show superiority in reducing exacerbations and morbidity (P > .05). Phenotypes that more than doubled the odds FeNO alone identified uncontrolled asthma included adolescence, non-adherence, high atopy (>6+), and baseline FeNO >35 ppb, whereas obesity, FEF25-75% < 65% predicted, and bronchodilator response >10% decreased the odds. Uncontrolled asthma by FeNO alone (F) vs guidelines alone (G) showed overall F/G > 1.0 in adolescents, but <1.0 in younger patients unless the FeNO threshold was reduced to >20 ppb. CONCLUSION: Our study suggests that age and phenotypes play a key role in FeNO discordance compared with the conventional guideline-based uncontrolled asthma. The FeNO-based therapeutic algorithm, if confirmed further, could provide the clinician with an effective asthma management tool. The clinical implication could improve future FeNO-based RCTs and treatment decision algorithms in managing asthma by considering phenotypes and age-dependent FeNO thresholds.


Assuntos
Asma/diagnóstico , Testes Respiratórios/métodos , Óxido Nítrico/análise , Adolescente , Fatores Etários , Algoritmos , Criança , Expiração , Feminino , Humanos , Masculino
17.
PLoS One ; 14(5): e0215427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31059515

RESUMO

Perioperative anemia frequently occurs in patients undergoing orthopedic surgery. We aimed to evaluate the efficacy of perioperative intravenous iron therapy (IVIT) on transfusion and recovery profiles during orthopedic surgery. We searched PubMed, Embase, Cochrane, and Google Scholar for eligible clinical trials (randomized controlled trials, RCTs; case-control studies, CCSs) in comparing IVIT and no iron therapy, up to September 2018. Primary outcomes were the effects of IVIT on the proportion of patients transfused and units of red blood cells (RBCs) transfused perioperatively. Secondary outcomes were the effects of IVIT on recovery profiles, such as length of hospital stay (LOS), post-operative infection, and mortality. Subgroup analysis was performed based on iron dose (low: ≤ 300 mg, high: > 400 mg), IVIT period (pre-operative, post-operative, perioperative), and study design. We identified 12 clinical trials (4 RCTs with 616 patients and 8 CCSs with 1,253 patients). IVIT significantly reduced the proportion of patients transfused by 31% (RR, 0.69; P = 0.0002), and units of RBCs transfused by 0.34 units/person (MD, -0.34; P = 0.0007). For subgroup analysis by iron dose, low- or high-dose IVIT significantly reduced the proportion of patients transfused (RR, 0.73, P = 0.005; RR, 0.68, P = 0.008), and RBC units transfused (MD, -0.47, P < 0.0001; MD, -0.28, P = 0.04). For subgroup analysis by period, IVIT administered post-operatively significantly reduced the proportion of patients transfused (post-operative: RR, 0.60, P = 0.002; pre-operative: RR, 0.74, P = 0.06) and RBC units transfused (post-operative: MD, -0.44, P <0.00001; pre-operative: MD, -0.29, P = 0.06). For subgroup analysis by study design, IVIT decreased the proportion of patients transfused and RBC units transfused in the group of CCSs, but IVIT in the group of RCTs did not. IVIT significantly shortened LOS by 1.6 days (P = 0.0006) and reduced post-operative infections by 33% (P = 0.01). IVIT did not change mortality. Perioperative IVIT during orthopedic surgery, especially post-operatively, appears to reduce the proportion of patients transfused and units of RBCs transfused, with shorter LOS and decreased infection rate, but no change in mortality rate. These were only found in CCSs and not in RCTs due to the relatively small number of RCTs with low to high risk of bias.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Ferro/administração & dosagem , Procedimentos Ortopédicos/métodos , Humanos , Infusões Intravenosas , Tempo de Internação , Assistência Perioperatória/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
J Biol Chem ; 294(6): 1794-1806, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30530492

RESUMO

Lipid transport is an essential process with manifest importance to human health and disease. Phospholipid flippases (P4-ATPases) transport lipids across the membrane bilayer and are involved in signal transduction, cell division, and vesicular transport. Mutations in flippase genes cause or contribute to a host of diseases, such as cholestasis, neurological deficits, immunological dysfunction, and metabolic disorders. Genome-wide association studies have shown that ATP10A and ATP10D variants are associated with an increased risk of diabetes, obesity, myocardial infarction, and atherosclerosis. Moreover, ATP10D SNPs are associated with elevated levels of glucosylceramide (GlcCer) in plasma from diverse European populations. Although sphingolipids strongly contribute to metabolic disease, little is known about how GlcCer is transported across cell membranes. Here, we identify a conserved clade of P4-ATPases from Saccharomyces cerevisiae (Dnf1, Dnf2), Schizosaccharomyces pombe (Dnf2), and Homo sapiens (ATP10A, ATP10D) that transport GlcCer bearing an sn2 acyl-linked fluorescent tag. Further, we establish structural determinants necessary for recognition of this sphingolipid substrate. Using enzyme chimeras and site-directed mutagenesis, we observed that residues in transmembrane (TM) segments 1, 4, and 6 contribute to GlcCer selection, with a conserved glutamine in the center of TM4 playing an essential role. Our molecular observations help refine models for substrate translocation by P4-ATPases, clarify the relationship between these flippases and human disease, and have fundamental implications for membrane organization and sphingolipid homeostasis.


Assuntos
Transportadores de Cassetes de Ligação de ATP/química , Adenosina Trifosfatases/química , Proteínas de Membrana Transportadoras/química , Modelos Moleculares , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/enzimologia , Proteínas de Schizosaccharomyces pombe/química , Schizosaccharomyces/enzimologia , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Transporte Biológico Ativo , Glucosilceramidas/química , Glucosilceramidas/metabolismo , Células HeLa , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Mutagênese Sítio-Dirigida , Domínios Proteicos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo
19.
FASEB J ; 33(3): 3087-3096, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509129

RESUMO

P4-ATPases, a subfamily of P-type ATPases, were initially identified as aminophospholipid translocases in eukaryotic membranes. These proteins generate and maintain membrane lipid asymmetry by translocating aminophospholipids (phosphatidylserine and phosphatidylethanolamine) from the exoplasmic/lumenal leaflet to the cytoplasmic leaflet. The human genome encodes 14 P4-ATPases, and the cellular localizations, substrate specificities, and cellular roles of these proteins were recently revealed. Numerous P4-ATPases, including ATP8A1, ATP8A2, ATP11A, ATP11B, and ATP11C, transport phosphatidylserine. By contrast, ATP8B1, ATP8B2, and ATP10A transport phosphatidylcholine but not aminophospholipids, although there is a discrepancy regarding the substrate of ATP8B1 in the literature. Some yeast and plant P4-ATPases can also translocate phosphatidylcholine. At least 2 P4-ATPases (ATP8A2 and ATP8B1) are associated with severe human diseases, and other P4-ATPases are implicated in various pathophysiologic conditions in mouse models. Here, we discuss the cellular functions of phosphatidylcholine flippases and suggest a model for the phenotype of progressive familial intrahepatic cholestasis 1 caused by a defect in ATP8B1.-Shin, H.-W., Takatsu, H. Substrates of P4-ATPases: beyond aminophospholipids (phosphatidylserine and phosphatidylethanolamine).


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo , Adenosina Trifosfatases/química , Adenosina Trifosfatases/genética , Sequência de Aminoácidos , Animais , Membrana Celular/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Modelos Biológicos , Modelos Moleculares , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , Proteínas de Transferência de Fosfolipídeos/química , Proteínas de Transferência de Fosfolipídeos/genética , Fosfolipídeos/metabolismo , Especificidade por Substrato
20.
Food Chem ; 266: 161-169, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30381171

RESUMO

Untargeted metabolomics unraveled the effects of varying substrates (soybean, wheat, and rice) and inocula (Aspergillus oryzae and Bacillus amyloliquefaciens) on metabolite compositions of koji, a starter ingredient in various Asian fermented foods. Multivariate analyses of the hyphenated mass spectrometry datasets for different koji extracts highlighted 61 significantly discriminant primary metabolites (sugars and sugar alcohols, organic acids, amino acids, fatty acids, nucleosides, phenolic acids, and vitamins) according to varying substrates and inocula combinations. However, 59 significantly discriminant secondary metabolites were evident for koji-types with varying substrates only, viz., soybean (flavonoids, soyasaponins, and lysophospholipids), wheat (flavones and lysophospholipids), and rice (flavonoids, fatty acids derivatives, and lysophospholipids). Independently, the substrates influenced primary metabolite compositions in koji (soybean > wheat, rice). The inocula choice of A. oryzae engendered higher carbohydrates, organic acids, and lipid derivative levels commensurate with high α-amylase and ß-glucosidase activities, while B. amyloliquefaciens affected higher amino acids levels, in respective koji types.


Assuntos
Aspergillus oryzae/metabolismo , Bacillus amyloliquefaciens/metabolismo , Metabolômica , Oryza/metabolismo , Soja/metabolismo , Triticum/metabolismo , Aminoácidos/análise , Carboidratos/análise , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Cromatografia Gasosa-Espectrometria de Massas , Concentração de Íons de Hidrogênio , Hidroxibenzoatos/análise , Análise de Componente Principal , Vitaminas/análise , alfa-Amilases/metabolismo , beta-Glucosidase/metabolismo
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