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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. METHODS: This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. RESULTS: A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90-23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09-1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19-0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-ß, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001). CONCLUSION: In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. TRIAL REGISTRATION: This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.
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Restrição Calórica , Estilo de Vida , Hepatopatia Gordurosa não Alcoólica , Obesidade , Sobrepeso , Humanos , Masculino , Feminino , Restrição Calórica/métodos , China , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/complicações , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/terapia , Obesidade/complicações , Sobrepeso/terapia , Sobrepeso/complicações , Sobrepeso/dietoterapia , Adulto , Fígado/metabolismo , Índice de Massa Corporal , Exercício Físico/fisiologia , Aconselhamento/métodosRESUMO
Alvarez lenses, a kind of passive zoom lenses with reconfigurable focus, have been widely applied in optics but very few at lower frequencies such as in a microwave band, where the phase approximation for Alvarez lenses becomes inaccurate. In this article, we propose a design of a modified Alvarez lens with phase compensation for microwave, which consists of a pair of transmissive metasurfaces with high efficiency. The proposed metasurface consists of miniaturized units with the capability of full 2π phase modulation. We further analyze the phase distribution principle of the Alvarez lens and proposed a phase compensation scheme. The simulation results confirm that the proposed modified Alvarez lens has a very good dynamic focal length with theoretical expectation and can be continuously adjusted from 100 to 200 mm.
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BACKGROUND: Renal calyx diverticulum refers to a cystic lesion covered with the transitional epithelium in the renal parenchyma. Although there is no clear evidence that calyx diverticulum can cause hypertension, there exists a close association between the two, and there are few related reports. Herein, we reported the case of a child with renal calyx diverticulum complicated with hypertension and summarized the diagnosis and treatment. CASE PRESENTATION: Physical examination of the patient, an 11-year-old child, revealed a left renal cyst with hypertension (155/116 mmHg). There were no related symptoms. Routine urine and blood biochemical examinations showed no abnormalities. Imaging revealed left renal cyst compression causing the hypertension. She underwent renal cyst fluid aspiration and injection of a sclerosing agent into the capsule, but her blood pressure increased again 3 days postoperatively. Color Doppler ultrasonography showed that the size of the left renal cyst was the same as that preoperatively. To further confirm the diagnosis, cystoscopic retrograde ureteropyelography was performed to confirm the diagnosis of renal calyx diverticulum. Subsequently, renal calyceal diverticulum resection and calyx neck enlargement were performed. The operation went smoothly and the blood pressure returned to normal postoperatively. No abnormalities were noted at the 7-month postoperative follow-up. CONCLUSION: There exists an association between renal calyx diverticulum and hypertension. Therefore, hypertension can be considered a surgical indication for renal calyx diverticulum. Moreover, renal calyceal diverticulum in children can be easily misdiagnosed as a renal cyst. Therefore, it is important to be vigilant to prevent a series of complications, such as postoperative urine leakage, in such cases.
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Divertículo , Hipertensão , Doenças Renais Císticas , Criança , Divertículo/diagnóstico , Divertículo/diagnóstico por imagem , Feminino , Humanos , Hipertensão/complicações , Rim/patologia , Cálices Renais/diagnóstico por imagem , Cálices Renais/patologia , Cálices Renais/cirurgia , Doenças Renais Císticas/diagnósticoRESUMO
BACKGROUND: We admitted a child with a duplex kidney combined with preoperative rupture of nephroblastoma and used this case to discuss the clinical features and treatment of this disease. CASE PRESENTATION: We retrospectively analyzed the clinical data of a 5-year-old girl with preoperative duplex kidney rupture combined with inferior nephroblastoma who was admitted to the Fourth Hospital of Baotou. In addition, we reviewed the relevant literature. The patient's details were as follows: weight, 17 kg; height, 108 cm; and body surface area, 0.7 m2. Abdominal ultrasound for abdominal pain revealed the presence of a left-sided renal mass; enhanced abdominal computed tomography further confirmed it to be a left-sided duplex kidney measuring approximately 6 × 5 × 5 cm, with a rupture originating from the lower kidney. The PubMed database was searched from 2010 to 2020 for the terms "Wilms' tumor" and "Duplex" and "Wilms' tumor" and "Rupture." The treatment plan was preoperative chemotherapy (vincristine/dactinomycin, VA regimen) + left kidney tumor radical surgery + postoperative chemotherapy (actinomycin-D/VCR/doxorubicin, AVD regimen). Postoperative pathology revealed an International Society of Pediatric Oncology intermediate-risk stage-3 nephroblastoma (mixed type) in the left kidney. Literature review was performed with 71 cases meeting the set criteria with an aim to analyze and summarize the clinical characteristics and treatment of patients with ruptured nephroblastoma and duplex kidney combined with nephroblastoma. CONCLUSIONS: To our knowledge, no previous studies have reported preoperative duplex kidney combined with nephroblastoma rupture. In patients with this condition, preoperative chemotherapy is recommended when the vital signs are stable and tumor resection can be performed after the tumor has shrunk to prevent secondary spread. If the patient's vital signs are unstable, emergency exploratory surgery is needed. If the nephroblastoma rupture is old and limited, surgery can be performed when the tumor size is small.
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Neoplasias Renais , Tumor de Wilms , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Pré-Escolar , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Estudos Retrospectivos , Vincristina/uso terapêutico , Tumor de Wilms/diagnóstico , Tumor de Wilms/diagnóstico por imagemRESUMO
The colinearity of canonical modular polyketide synthases, which creates a direct link between multienzyme structure and the chemical structure of the biosynthetic end-product, has become a cornerstone of knowledge-based genome mining. Herein, we report genetic and enzymatic evidence for the remarkable role of an enoylreductase in the polyketide synthase for azalomycin F biosynthesis. This internal enoylreductase domain, previously identified as acting only in the second of two chain extension cycles on an initial iterative module, is shown to also catalyze enoylreduction in trans within the next module. The mechanism for this rare deviation from colinearity appears to involve direct cross-modular interaction of the reductase with the longer acyl chain, rather than back transfer of the substrate into the iterative module, suggesting an additional and surprising plasticity in natural PKS assembly-line catalysis.
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Macrolídeos/metabolismo , Policetídeo Sintases/metabolismo , Biocatálise , Macrolídeos/química , Conformação Molecular , Oxirredução , Policetídeo Sintases/químicaRESUMO
The access of new energy improves the flexibility of distribution network operation, but also leads to more complex mechanism of line loss. Therefore, starting from the nonlinear, fluctuating and multi-scale characteristics of line loss data, and based on the idea of decomposition prediction, this paper proposes a new method of line loss frequency division prediction based on wavelet transform and BIGRU-LSTM (Bidirectional Gated Recurrent Unit-Long Short Term Memory Network).Firstly, the grey relation analysis and the improved NARMA (Nonlinear Autoregressive Moving Average) correlation analysis method are used to extract the non-temporal and temporal influencing factors of line loss, and the corresponding feature data set is constructed. Then, the historical line loss data is decomposed into physical signals of different frequency bands by using wavelet transform, and the multi-dimensional input data of the prediction network is formed with the above characteristic data set. Finally, the BIGRU-LSTM prediction network is built to realize the probabilistic prediction of high-frequency and low-frequency components of line loss. The effectiveness and applicability of the method proposed in this paper were verified through numerical simulation. By dividing the line loss data into different frequency bands for frequency prediction, the mapping relationship between different line loss components and influencing factors was accurately matched, thereby improving the prediction accuracy.
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Redes Neurais de Computação , Análise de Ondaletas , AlgoritmosRESUMO
Objective: To explore the application effect of enhanced recovery after surgery (ERAS) perioperative plan in the treatment of complex appendicitis in children, and further enrich the implementation plan of ERAS in the field of pediatric surgery. Method: This study selected 122 children who underwent laparoscopic complex appendectomy at Inner Mongolia Maternal and Child Health Hospital and Baotou Fourth Hospital from August 2018 to July 2022, and randomly divided them into a traditional surgery group (TS) and an enhanced recovery surgery group (ERAS). The changes of white blood cell (WBC), hypersensitive C-reactive protein (CRP), pro Calcitonin (PCT) and interleukin 6 (IL-6) before and after surgery were compared. The degree of pain, recovery time of intestinal function, length of hospital stay, hospital costs, postoperative complications and parental satisfaction were compared between the two groups. Result: The WBC and CRP levels in the ERAS group at 6â h after surgery, as well as the IL-6 levels on the 3rd day after surgery, were lower than those in the TS group. Meanwhile, the analgesic effect of ERAS group at 3â h and 6â h after surgery was better than that of TS group. And the ERAS group had a shorter postoperative first exhaust time, fewer overall hospital stays, and lower hospitalization costs. In addition, the ERAS group had high parental satisfaction during hospitalization. There was no statistically significant difference in postoperative complications between the two groups of children. Conclusion: ERAS can promote postoperative recovery of children, reduce surgical stress, save family medical expenses, alleviate the pain of children, and improve parental satisfaction. It is a safe and effective method for treating complex appendicitis in children.
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BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs which function as novel regulators in human cancers. In this study, we aimed to investigate the functional roles and related molecular mechanisms of circ_0006282 in gastric cancer (GC) progression. METHODS: Fifty-five GC patients were enrolled in this study. GC cells (AGS and HGC-27) and normal cells (GES-1) were cultured in RPMI1640 added with 10% FBS and 1% penicillin-streptomycin. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the expression levels of circ_0006282, transcription elongation factor B subunit 1 (TCEB1) mRNA, miR-144-5p and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein ß (YWHAB; also known as 14-3-3ß). RNase R assay was used to determine the characteristic of circ_0006282. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were employed for cell proliferation. Transwell assay was conducted for cell migration and invasion. Western blot assay was carried out to measure the protein levels of Cyclin D1, matrix metalloprotein 9 (MMP9) and YWHAB. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were adopted to analyze the interaction between miR-144-5p and circ_0006282 or YWHAB. Murine xenograft model assay was performed to explore the function of circ_0006282 in vivo. RESULTS: Circ_0006282 level was increased in GC tissues and cells compared to normal tissues and cells. Silencing of circ_0006282 restrained GC cell proliferation, migration and invasion. For mechanism analysis, circ_0006282 was identified to function as the sponge for miR-144-5p to positively regulate YWHAB expression in GC cells. Moreover, miR-144-5p inhibition or YWHAB overexpression effectively reversed the impacts of circ_0006282 knockdown on GC cell growth and motility. Additionally, circ_0006282 knockdown blocked tumor growth of GC in vivo. CONCLUSION: Circ_0006282 facilitated the malignant behaviors of GC cells through circ_0006282/miR-144-5p/YWHAB axis.
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Objective:To analysis the clinical and histopathological features, and the effect of surgical treatment and adjuvant therapy for the survival in patients of head and neck mucosal melanomaï¼HNMMï¼. Method:A retrospective analysis was conducted on the clinical data of 46 patients with HNMM, and the factors related to survival were analyzed. Kaplan-Meier analysis was used for survival analysis. Log-rank test was used for univariate analysis, and COX proportional hazard model was used for multivariate analysis. Result:The 3 and 5 year cumulative survival rates of 46 patients with HNMM were 47.5% and 34.1%, respectively, and the median survival time was 36 months. Univariate analysis revealed that the factors affecting survival rates in patients with HNMM included tumor staging, surgical margins, postoperative targeted therapy, distant metastasis and local recurrenceï¼P<0.05ï¼. Multiple factor COX regression analysis showed that distant metastasis, tumor staging, surgical margins were independent risk factors for survival rates in patients with HNMM, and postoperative targeted therapy was the protective factor. Conclusion:HNMM is of high malignancy and low survival rate. Early diagnosis and complete surgical resection are the primary methods to improve the survival, and postoperative targeted therapy may be an intervention to improve the survival.
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Neoplasias de Cabeça e Pescoço , Melanoma , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de SobrevidaRESUMO
BACKGROUND: Substantial research has been conducted focusing on student outcomes in mathematics courses in order to better understand the ways in which these outcomes depend on the underlying instructional methodologies found in the courses. From 2009 to 2014, the Mathematical Association of America (MAA) studied Calculus I instruction in United States (US) colleges and universities in the Characteristics of Successful Programs of College Calculus (CSPCC). One aspect of this study attempted to understand the impact of these courses on student experience. RESULTS: In this paper, we describe results from an examination of the effect of course structure on students' attitudes and beliefs across different versions of Calculus I at a large research university in the USA. To do this, we implemented a follow-up study of the national MAA study of calculus programs in part to identify potential relationships between various course structures and changes in attitudes and beliefs during the course. We compare our results both internally across these course structures and to the national data set. CONCLUSIONS: We find that the statistically significant changes measured in confidence and enjoyment exhibit differences across the different calculus implementations and that these changes are statistically independent of the underlying student academic backgrounds as shown by standardized test scores and high school GPA. This suggests that these observed changes in attitudes and beliefs relate to the experience in our varied course structures and not to the academic characteristics of students as they enter the course. In addition to our findings, we show how this national study can be used locally to study effects of courses on student affective traits.
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MicroRNAs (miRNAs) are strongly implicated in various cancers, including prostate cancer. Recently, microRNA-455-3p (miR-455-3p) has been shown to be aberrantly expressed in many tumor tissues, but its functions in tumorigenesis remain unknown. In this study, we investigated the role of miR-455-3p in prostate cancer. We found that miR-455-3p is markedly downregulated in prostate cancer cell lines and clinical tumor specimens. Gain-of-function and loss-of-function studies showed that miR-455-3p promotes prostate cancer cell growth both in vitro and in vivo. Bioinformatics analysis and Luciferase reporter assays demonstrated that miR-455-3p directly targets and suppresses eIF4E, the rate-limiting factor for cap-dependent translation, which plays important roles in the initiation and progression of prostate cancers. Further studies demonstrated that miR-455-3p inhibits cap-dependent translation and the proliferation of prostate cancer cells through targeting eIF4E. Taken together, our findings suggest that miR-455-3p functions as a tumor suppressor by directly targeting eIF4E in prostate carcinogenesis and may be used as a potential target for therapeutic intervention in prostate cancer.
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Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4F em Eucariotos/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional/métodos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Transplante de NeoplasiasRESUMO
Earlier work provided direction for development of responsive drug delivery systems based on modulation of the structure, amphiphilicity, and surface density of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. In this work, we describe the sequential and competitive adsorption behavior of such peptides at pendant PEO layers. Three cationic peptides were used for this purpose: the arginine-rich, amphiphilic peptide WLBU2, a peptide chemically identical to WLBU2 but of scrambled sequence (S-WLBU2), and the non-amphiphilic peptide poly-L-arginine (PLR). Optical waveguide lightmode spectroscopy (OWLS) was used to quantify the rate and extent of peptide adsorption and elution at surfaces coated with PEO. UV spectroscopy and time-of-flight secondary ion mass spectrometry (TOF-SIMS) were used to quantify the extent of peptide exchange during the course of sequential and competitive adsorption. Circular dichroism (CD) was used to evaluate conformational changes after adsorption of peptide mixtures at PEO-coated silica nanoparticles. Results indicated that amphiphilic peptides are able to displace adsorbed, non-amphiphilic peptides in PEO layers, while non-amphiphilic peptides were not able to displace more amphiphilic peptides. In addition, peptides of greater amphiphilicity dominated the adsorption at the PEO layer from mixtures with less amphiphilic or non-amphiphilic peptides.
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Peptídeos Catiônicos Antimicrobianos/química , Arginina/química , Peptídeos/química , Polietilenoglicóis/química , Adsorção , Peptídeos Catiônicos Antimicrobianos/metabolismo , Ligação Competitiva , Dicroísmo Circular , Interações Hidrofóbicas e Hidrofílicas , Cinética , Espectrometria de Massas/métodos , Peptídeos/metabolismo , Polietilenoglicóis/metabolismo , Conformação Proteica , Espectrofotometria Ultravioleta , Propriedades de SuperfícieRESUMO
In earlier work, we have provided direction for development of responsive drug delivery systems based on modulation of structure and amphiphilicity of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. Amphiphilicity promotes retention of the peptides within the hydrophobic inner region of the PEO brush layer. In this work, we describe the effects of peptide surface density on the conformational changes caused by peptide-peptide interactions, and show that this phenomenon substantially affects the rate and extent of peptide elution from PEO brush layers. Three cationic peptides were used in this study: the arginine-rich amphiphilic peptide WLBU2, the chemically identical but scrambled peptide S-WLBU2, and the non-amphiphilic homopolymer poly-l-arginine (PLR). Circular dichroism (CD) was used to evaluate surface density effects on the structure of these peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. UV spectroscopy and a quartz crystal microbalance with dissipation monitoring (QCM-D) were used to quantify changes in the extent of peptide elution caused by those conformational changes. For amphiphilic peptides at sufficiently high surface density, peptide-peptide interactions result in conformational changes which compromise their resistance to elution. In contrast, elution of a non-amphiphilic peptide is substantially independent of its surface density, presumably due to the absence of peptide-peptide interactions. The results presented here provide a strategy to control the rate and extent of release of bioactive peptides from PEO layers, based on modulation of their amphiphilicity and surface density.
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Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Polietilenoglicóis/química , Adsorção , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/química , Dicroísmo Circular , Dados de Sequência Molecular , Nanopartículas/química , Peptídeos/química , Estrutura Secundária de Proteína , Técnicas de Microbalança de Cristal de Quartzo , Propriedades de SuperfícieRESUMO
Passage of blood through a sorbent device for removal of bacteria and endotoxin by specific binding with immobilized, membrane-active, bactericidal peptides holds promise for treating severe blood infections. Peptide insertion in the target membrane and rapid/strong binding is desirable, while membrane disruption and release of degradation products to the circulating blood is not. Here we describe interactions between bacterial endotoxin (lipopolysaccharide, LPS) and the membrane-active, bactericidal peptides WLBU2 and polymyxin B (PmB). Analysis of the interfacial behavior of mixtures of LPS and peptide using air-water interfacial tensiometry and optical waveguide lightmode spectroscopy strongly suggests insertion of intact LPS vesicles by the peptide WLBU2 without vesicle destabilization. In contrast, dynamic light scattering (DLS) studies show that LPS vesicles appear to undergo peptide-induced destabilization in the presence of PmB. Circular dichroism spectra further confirm that WLBU2, which shows disordered structure in aqueous solution and substantially helical structure in membrane-mimetic environments, is stably located within the LPS membrane in peptide-vesicle mixtures. We therefore expect that presentation of WLBU2 at an interface, if tethered in a fashion which preserves its mobility and solvent accessibility, will enable the capture of bacteria and endotoxin without promoting reintroduction of endotoxin to the circulating blood, thus minimizing adverse clinical outcomes. On the other hand, our results suggest no such favorable outcome of LPS interactions with polymyxin B.
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Peptídeos Catiônicos Antimicrobianos/metabolismo , Lipopolissacarídeos/metabolismo , Polimixina B/metabolismo , Tensoativos/metabolismo , Adsorção , Ar , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Dicroísmo Circular , Interações Hidrofóbicas e Hidrofílicas , Cinética , Lipopolissacarídeos/química , Dados de Sequência Molecular , Peso Molecular , Tamanho da Partícula , Polimixina B/química , Polimixina B/farmacologia , Ligação Proteica/efeitos dos fármacos , Tensão Superficial/efeitos dos fármacos , Tensoativos/química , Tensoativos/farmacologia , ÁguaRESUMO
A more quantitative understanding of peptide loading and release from polyethylene oxide (PEO) brush layers will provide direction for development of new strategies for drug storage and delivery. In this work we recorded selected effects of peptide structure and amphiphilicity on adsorption into PEO brush layers based on covalently stabilized Pluronic(®)F 108. Optical waveguide lightmode spectroscopy and circular dichroism measurements were used to characterize the adsorption of poly-l-glutamic acid, poly-l-lysine, and the cationic amphiphilic peptide WLBU2, to the brush layers. The structure of WLBU2 as well as that of the similarly-sized homopolymers was controlled between disordered and more ordered (helical) forms by varying solution conditions. Adsorption kinetic patterns were interpreted with reference to a simple model for protein adsorption, in order to evaluate rate constants for peptide adsorption and desorption from loosely and tightly bound states. While more ordered peptide structure apparently promoted faster adsorption and elution rates, resistance to elution while in the PEO layer was dependent on peptide amphiphilicity. The results presented here are compelling evidence of the potential to create anti-fouling surface coatings capable of storing and delivering therapeutics.
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Peptídeos/química , Polietilenoglicóis/química , Adsorção , Cinética , Poloxâmero/química , Conformação ProteicaRESUMO
An experimentally based, quantitative understanding of the entrapment and function of small peptides within PEO brush layers does not currently exist. Earlier work provided a rationale for expecting that an ordered, compact peptide will enter the PEO phase more readily than a peptide of similar size that adopts a less ordered, less compact form, and that amphiphilicity will promote peptide retention within the hydrophobic region of the PEO brush. Here we more deliberately describe criteria for peptide integration and structural change within the PEO brush, and discuss the reversibility of peptide entrapment with changing solvent conditions. For this purpose, circular dichroism (CD) was used to record the adsorption and conformational changes of (amphiphilic) WLBU2 and (non-amphiphilic) polyarginine peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. Peptide conformation was controlled between disordered and α-helical forms by varying the concentration of perchlorate ion. We show an initially more ordered (α-helical) structure promotes peptide adsorption into the PEO layer. Further, a partially helical peptide undergoes an increase in helicity after entry, likely due to concomitant loss of capacity for peptide-solvent hydrogen bonding. Peptide interaction with the PEO chains resulted in entrapment and conformational change that was irreversible to elution with changing solution conditions in the case of the amphiphilic peptide. In contrast, the adsorption and conformational change of the non-amphiphilic peptide was reversible. These results indicate that responsive drug delivery systems based on peptide-loaded PEO layers can be controlled by modulation of solution conditions and peptide amphiphilicity.
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Peptídeos/química , Peptídeos/isolamento & purificação , Polietilenoglicóis/química , Adsorção , Sequência de Aminoácidos , Cátions/química , Engenharia Química , Dicroísmo Circular , Sistemas de Liberação de Medicamentos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Dados de Sequência Molecular , Estrutura Molecular , Nanopartículas/química , Conformação Proteica , Estrutura Secundária de Proteína , Dióxido de Silício , Solventes , Espectrofotometria , Propriedades de Superfície , TensoativosRESUMO
The aim of this study was to investigate prevalences of hyperuricemia and the metabolic syndrome (MS) in the Hangzhou population, and the relationship between serum uric acid and the MS. A cross-sectional study was conducted among 4155 subjects (2614 men and 1541 women) aged 20-80 years, recruited through a health check program in Hangzhou, China. Biochemical and haematological parameters were measured by standard methods. The diagnosis of the MS is made when three or four of the following criteria are met: 1) body mess index (BMI) >or= 25; 2) systolic blood pressure >or= 140 mmHg or diastolic blood pressure >or= 90 mmHg; 3) fasting triacyglycerol >or= 1.7 mmol/L (150 mg/dL), high density lipoprotein cholesterol (HDL-C) < 0.9 mmol/L (35 mg/dL) in men and <1.0 mmol/L (39 mg/dL) in women; 4) fasting glucose >or= 6.1 mmol/L (109 mg/dL). Hyperuricemia is defined by cut-off values of > 420 mumol/L for men and > 360 mumol/L for women. Prevalences were 16.9% (N=702) for hyperuricemia and 8.4% (N=349) for the MS. Serum uric acid concentration was significantly higher in males than in females (p<0.0001), and significantly higher in subjects with obesity, dyslipidemia and hypertension compared with those without. In the partial correlation analysis, after controlling for gender, age and creatinine, serum uric acid concentration was significantly positively correlated with BMI (r=0.301, p<0.0001), systolic blood pressure (r=0.151, p<0.0001), diastolic blood pressure (r=0.168, p<0.0001), total cholesterol (r=0.144, p<0.0001) and triacyglycerol (r=0.234, p<0.0001). Results suggest that increased serum uric acid concentration is associated with an increased prevalence of metabolic disorders such as obesity, dyslipidemia and hypertension in the Hangzhou population.