Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 420
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
J Biol Chem ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484726

RESUMO

Over the past decade, thousands of long non-coding RNAs (lncRNAs) have been identified, many of which play crucial roles in normal physiology and human disease. LncRNAs can interact with chromatin and then recruit protein complexes to remodel chromatin states, thus regulating gene expression. However, how lncRNA-chromatin interactions contribute to their biological functions is largely unknown. Here, we collected and constructed an atlas of 188,647 lncRNA-chromatin interactions in human and mouse. All lncRNAs showed diverse epigenetic modification patterns at their binding sites, especially the marks of enhancer activity. Functional analysis of lncRNA target genes further revealed that lncRNAs could exert their functions by binding to both promoter and distal regulatory elements, especially the distal regulatory elements. Intriguingly, many important pathways were observed to be widely regulated by lncRNAs through distal binding. For example, NEAT1, a cancer lncRNA, controls 13.3% of genes in the PI3K-AKT signaling pathway by interacting with distal regulatory elements. In addition, "two-gene" signatures composed of a lncRNA and its distal target genes, such as HOTAIR-CRIM1, provided significant clinical benefits relative to the lncRNA alone. In summary, our findings underscored that lncRNA-distal interactions were essential for lncRNA functions, which would provide new clues to understand the molecular mechanisms of lncRNAs in complex disease.

2.
J Immunol ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484729

RESUMO

Intrathecal morphine infusion is often applied to treat chronic pain related to cancer and other conditions. However, persistent pain can be caused by nerve compression because of granuloma formation. In this study, a mouse model of morphine-induced granuloma formation by intrathecal catheterization morphine infusion into the atlanto-occipital membrane of the foramen magnum was established in wild-type mice, MrgprB2 mutant (MrgprB2-/-) mice, and in mast cell-deficient W-sash c-kit mutant (KitW-sh/W-sh) mice. Heat-related pain after surgery was performed to investigate the antipain effect of morphine. H&E staining and immunofluorescence staining of the spinal cord were applied to analyze the mechanism of granuloma formation. Morphine-induced mast cell degranulation was assessed by measuring the Ca2+ influx and mediator release. Anaphylactoid reactions were measured after s.c. morphine infusion to the paws. Chemokine release by mast cells was determined by Human XL Cytokine Array. Experiments with wild-type, MrgprB2 mutant, and mast cell-deficient W-sash c-kit mutant mice demonstrated that morphine activated mast cells and inflammatory cell aggregation through MrgprB2 in intrathecal infusion sites. The chemokine production of human mast cells demonstrated that granuloma formation is correlated with chemokines release. In addition, morphine activated mouse primary mast cells and de novo chemokine synthesis via the MRGPRX2 in human LAD2 cells. We concluded that granuloma formation during intrathecal morphine infusion was associated with MrgprB2/X2. Reducing MRGPRX2 potentially blocks morphine-induced side effects, including granuloma formation.

3.
Int Immunopharmacol ; 75: 105832, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31473434

RESUMO

We recently found that Sodium butyrate (NaB) possesses anti-inflammatory effects in diabetic nephropathy (DN) mouse model and in high-glucose induced mouse glomerular mesangial cells. Pyroptosis is a programmed cell death accompanied with the release of pro-inflammatory factors. Gasdermin D (GSDMD) is a novel discovered pivotal executive protein of pyroptosis, which can be cleaved by inflammatory caspases. The aim of our study is to verify if NaB have some effects against high-glucose induces pyroptosis in renal Glomerular endothelial cells (GECs). For this aim, human GECs were cultured and exposed to high-glucose. Exogenous NaB, caspase 1 inhibitor Ac-YVAD-CMK (A-Y-C) or knockdown GSDMD by siRNA were used. We found high glucose could increase Propidium Iodide (PI) positive cells and elevate release of lactate dehydrogenase (LDH), Interleukin 1 beta (IL-1ß) and Interleukin 18 (IL-18); protein levels of GSDMD, GSDMD N-terminal domain (GSDMD-N) and cleaved-caspase-1 were also elevated. Effect of NaB on LDH release and PI positive cells was further enhanced by inhibiting caspase 1-GSDMD. In addition, high glucose-induced nuclear factor kappa-B (NF-κB)/NF-κB inhibitor α (IκB-α) signaling pathway was reversed by NaB or A-Y-C administration. In conclusion, NaB could ameliorate high-glucose induced GECs via caspase1-GSDMD canonical pyroptosis pathway; and NF-κB/IκB-α signaling pathway was involved in it.

4.
J Craniofac Surg ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31449208

RESUMO

The effect of maxillary skeletal expansion (MSE) on upper airway in adolescent patients is not clear. The purpose of this study was to determine the upper airway airflow with MSE treatment using computational fluid dynamics analysis. Three-dimensional upper airway finite element models fabricated from cone beam computed tomography images were obtained before and after treatment in an adolescent patient with maxillary constriction. Turbulent analyses were applied. The nasal cavity (NC) was divided into 6 planes along the y-axis and the pharynx was divided into 7 planes in the z-axis. Changes in cross-sectional area, airflow velocity, pressure, and total resistance at maximum expiration and maximum inspiration were determined at each plane after MSE treatment. The greatest increase in area occurred in the oropharynx which was around 40.65%. The average increase in area was 7.42% in the NC and 22.04% in the pharynx. The middle part of pharynx showed the greatest increase of 212.81 mm and 217.99 mm or 36.58% and 40.66%, respectively. During both inspiration and expiration, airflow pressure decreased in both the NC and pharynx, which ranged from -11.34% to -23.68%. In the NC, the average velocity decrease was -0.18 m/s at maximum expiration (ME) and -0.13 m/s at maximum inspiration (MI). In the pharynx, the average velocity decrease was -0.07 m/s for both ME and MI. These results suggest that treatment of maxillary constriction using MSE appliance may show positive effects in improvement of upper airway cross-sectional areas and reduction of upper airway resistance and velocity.

5.
Dalton Trans ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432065

RESUMO

Herein, a novel series of PMo12-TiO2 composites deposited with Pt nanoparticles (NPs), namely X%Pt/PMo12/TiO2 (PMo12 = H3PMo12O40; X stands for wt% of Pt to the PMo12/TiO2 sample and X = 3, 5, 8, and 10), were prepared through a simple electrospinning/calcination method, followed by photoreduction. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed that Pt NPs with an average size of 10 ± 5 nm are well dispersed on the PMo12/TiO2 nanofibers. Photocatalytic tests revealed that the as-prepared Pt/PMo12/TiO2 composite catalysts exhibited excellent and persistent photocatalytic activity for removing methyl orange, tetracycline, Bisphenol A and Cr(vi) under visible-light illumination (λ > 420 nm). Among the as-prepared composites, the 8%Pt/PMo12/TiO2 sample displayed the best photocatalytic activity with the rate constants of 0.011 min-1 (MO), 0.043 min-1 (TC), 0.00615 min-1 (Bisphenol A) and 0.053 min-1 (Cr(vi)). The addition of POM PMo12 to the composites enhanced the visible-light adsorption and redox ability of TiO2. Furthermore, Pt NPs exhibited localized surface plasmon resonance (LSPR) absorption, therefore improving the absorption of visible light by PMo12/TiO2. Additionally, intense local electromagnetic fields resulted from LSPR, which greatly facilitated the separation of photo-produced charge carriers in Pt/PMo12/TiO2. The results of free radical- and hole-trapping tests suggested that ˙OH and ˙O2- were responsible for the degradation of MO/TC. Finally, the corresponding photocatalytic mechanism was proposed.

6.
J Bone Miner Metab ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414284

RESUMO

INTRODUCTION: Menopause can lead to osteoporosis, which is characterized by destruction of bone microstructure, poor mechanical properties, and prone to fracture. LIPUS can effectively promote bone formation and fracture healing. MSTN is a transforming growth factor-ß family member that acts as a negative regulator of skeletal muscle growth. A MSTN deficiency also has a positive effect on bone formation. However, whether LIPUS could inhibit bone loss and promote healing of bone injury of menopause through the inhibition of the MSTN signaling pathway has not been previously investigated. We herein investigated the effects of LIPUS on bone architecture, mechanical properties, the healing of bone defects, and its potential molecular mechanisms in ovariectomized rats. MATERIALS AND METHODS: The rats were randomly divided into three groups: sham ovariectomized group (Sham), ovariectomized model group (OVX), ovariectomized model with LIPUS therapy group (OVX + LIPUS). The OVX + LIPUS rats were treated with LIPUS (1.5 MHz, 30 mW/cm2) on the femur for 20 min/day that lasted for 19 days. RESULTS: LIPUS effectively improved the bone microstructure, increased mechanical properties and promoted the healing of bone defects in ovariectomized rats. Moreover, LIPUS effectively decreased the MSTN content in serum and quadriceps muscle in ovariectomized rats, and inhibited the expression of MSTN downstream signaling molecules and activated the Wnt signaling pathway in the femur. CONCLUSIONS: The present study shows that LIPUS improved osteoporosis and promoted bone defect healing in the ovariectomized rats may through the inhibition of the MSTN signal pathway.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31414394

RESUMO

Although the viscosity behavior of bacteria and extracellular polymeric substances (EPS) in flocculent activated sludge (FAS) and aerobic granular sludge (AGS) has been investigated, no studies have explored the role of viscosity in microbial attachment in pure culture. This study investigated the viscosity behavior of bacteria and EPS. The results showed that bacteria and their EPS exhibited non-Newtonian fluid and shear-thinning behavior. The viscosity of bacteria and EPS was 1.55-3.80 cP and 1.10-2.40 cP, respectively, while the attachment of bacteria (optical density at 600 nm) was 0.1426-3.1015. Bacteria with high attachment secreted EPS with a higher viscosity (2.40 cP), whereas those with weak attachment expressed EPS with a lower viscosity (1.10 cP). Viscosity and microbial attachment or extracellular polysaccharide (PS) content were significantly positively correlated. PS content was the source of bacterial viscosity, and ß-polysaccharide played a more important role in viscosity and microbial attachment than α-polysaccharide. Thus, viscosity plays a critical role in microbial attachment, and high viscosity and PS content result in high microbial attachment, which is beneficial to the granulation process of AGS.

8.
BMJ Open ; 9(8): e030866, 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31427343

RESUMO

INTRODUCTION: Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is characterised by recurring episodes of complete or partial upper airway collapse during sleep. Persistent OSAHS is associated with long-term consequences, such as growth failure, cardiovascular and neurocognitive problems in children. Different from the aetiology of OSAHS in adults, the most common cause of paediatric OSAHS is adenotonsillar hypertrophy. Adenotonsillectomy (AT) has been recommended as the first-line treatment of paediatric OSAHS. Several studies have suggested that retarded growth caused by OSAHS can improve after AT during the prepubertal period. This review will systematically search and summarise the available evidence on the effects of AT on children's growth. METHODS AND ANALYSIS: We will conduct electronic searches in MEDLINE (via PubMed), Embase, Google Scholar and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) or cohort studies that included a control group. Additional records will be searched by checking the references included in the selected studies and relevant reviews. At least two authors will undertake selection of studies and data extraction independently and in duplicate. The Cochrane Risk of Bias tool and Risk Of Bias In Non-randomised Studies-of Interventions will be used to assess the risk of bias of RCT and cohort studies, respectively. A random-effects model will be used for meta-analyses. Data synthesis and other analyses will be carried out using the RevMan V.5.3 software. The Grades of Recommendation, Assessment, Development and Evaluation will be used to assess the quality of the supporting evidence behind each main comparison. ETHICS AND DISSEMINATION: There is no ethical issue in this systematic review given that we will only include published studies. The results will be disseminated via peer-reviewed publications and social networks. PROSPERO REGISTRATION NUMBER: CRD42019125882.

9.
ACS Appl Mater Interfaces ; 11(32): 29466-29473, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31291082

RESUMO

In recent times, high-performance flexible pressure sensors that can be fabricated in an environmentally friendly and low-cost manner have received considerable attention owing to their potential applications in wearable health monitors and intelligent soft robotics. This paper proposes a highly sensitive flexible piezoresistive pressure sensor based on hybrid porous microstructures that can be designed and fabricated using a bio-inspired and low-cost approach employing the Epipremnum aureum leaf and sugar as the template. The sensitivity and detection limit of the obtained pressure sensor can be as high and low as 83.9 kPa-1 (<140 Pa) and 0.5 Pa, respectively. According to the mechanism and simulation analyses, the hybrid porous microstructures lower the effective elastic modulus of the sensor and introduce an additional pore resistance, which increases the contact area and conductive path with loads, thereby contributing to the high sensitivity that exceeds that of traditional microstructured pressure sensors. Real-time monitoring of human physiological signals such as finger pressing, voice vibration, swallowing activity, and wrist pulse is demonstrated for the proposed device. The high performance and easy fabrication of the hybrid porous microstructured sensor can encourage the development of a novel approach for the design and fabrication of future pressure sensors.

10.
Adv Mater ; 31(36): e1903387, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276253

RESUMO

Advancing thermoelectric n-type Mg3 Sb2 alloys requires both high carrier concentration offered by effective doping and high carrier mobility enabled by large grains. Existing research usually involves chalcogen doping on the anion sites, and the resultant carrier concentration reaches ≈3 × 1019 cm-3 or below. This is much lower than the optimum theoretically predicted, which suggets that further improvements will be possible once a highly efficient dopant is found. Yttrium, a trivalent dopant, is shown to enable carrier concentrations up to and above ≈1 × 1020 cm-3 when it is doped on the cation site. Such carrier concentration allows for in-depth understand of the electronic transport properties over a broad range of carrier concentrations, based on a single parabolic band approximation. As well as reasonably high carrier mobility in coarse-grain materials sintered by hot deforming and fusing of large pieces of ingots synthesized by melting, higher thermoelectric performance than earlier experimentally reported for n-type Mg3 Sb2 is found. In particular, the thermoelectric figure of merit, zT, is even higher than that of any known n-type thermoelectric, including Bi2 Te3 alloys, within 300-500 K. This might pave the way for Mg3 Sb2 alloys to become a realistic material for n-type thermoelectrics for sustainable applications.

11.
BMJ Open ; 9(7): e029270, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315871

RESUMO

OBJECTIVES: To evaluate the reporting quality of randomised controlled trial (RCT) abstracts presented at a leading international conference in sleep medicine (the SLEEP Annual Meeting), and to investigate the association between potential predictors and the reporting quality of trial abstracts in this field. DESIGN: Cross-sectional, research on research study. METHODS: A handsearch of the 2016-2018 SLEEP Annual Meeting abstract books was carried out to identify abstracts describing RCTs. Quality of reporting was assessed with the original 17-item CONSORT for Abstracts checklist. Univariable and multivariable linear regression analyses were performed to identify significant predictors of reporting quality. In addition, risk ratios were used to analyse the adequate reporting rate of each quality item by type of intervention and funding status. PRIMARY AND SECONDARY OUTCOME MEASURES: The overall quality score (OQS, range 0-17) in accordance with the CONSORT for Abstracts checklist (primary outcome), and the adequate reporting rate of each checklist item (secondary outcome). RESULTS: A total of 176 RCT abstracts were included and assessed. The mean OQS was 5.53 (95% CI 5.30 to 5.76). Only three quality items (objective, conclusions and funding) were adequately reported in most abstracts (>75%). None of the abstracts adequately reported authors, randomisation or outcome in the results section. According to the multivariable analysis, pharmacological interventions (p=0.018) and funding from the industry (p=0.025) were significantly associated with better reporting quality. CONCLUSIONS: The reporting quality of RCT abstracts presented at SLEEP Annual Meetings was suboptimal. Pharmacological intervention and funding from industry were significant predictors of better reporting quality. Joint efforts by authors and conference committees are needed to enhance the reporting quality of RCT abstracts presented at sleep medicine conferences, and thereby reduce relevant research waste in this field.

12.
J Clin Lab Anal ; : e22959, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31241209

RESUMO

BACKGROUND: Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) has shown to be overexpressed in several human cancers. The purpose of this study was to explore the expression of HPIP in endometrial cancer (EC) and its associated effects on disease. METHODS: A total of 113 EC patients at the Harbin Medical University Cancer Hospital between August 2011 and September 2012 were studied for immunohistochemistry analysis. HPIP expression was detected using real-time reverse transcription PCR, Western blotting, and immunohistochemistry. Prognostic value of HPIP expression was examined using multivariate Cox regression analysis and Kaplan-Meier method. RESULTS: The result of Western blotting indicated that HPIP protein expression is significantly high in normal tissues compared to EC tissues (P < 0.001). The expression of HPIP was significantly associated with FIGO stage (P < 0.001), histological grade (P < 0.001), depth of myometrial invasion (P < 0.001), and lymph node metastasis (P = 0.033). Kaplan-Meier analysis demonstrated that there was a significant difference in overall survival and disease-free survival between the two groups of patients stratified by HPIP expression level (log-rank, both P = 0.002). Patients with HPIP high expression had significantly shorter median survival time than those with HPIP low expression. Moreover, results of the multivariate analysis revealed that HPIP expression was an independent prognostic factor for predicting overall survival (P = 0.015) and disease-free survival (P = 0.017) in patients with EC. CONCLUSION: The present study provides evidence that HPIP predicts EC progression and poor survival, highlighting its potential as a therapeutic target for EC.

13.
Med Phys ; 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31220358

RESUMO

PURPOSE: Reducing dose level to achieve ALARA is an important task in diagnostic and therapeutic applications of computed tomography (CT) imaging. Effective image quality enhancement strategies are crucial to compensate for the degradation caused by dose reduction. In the past few years, deep learning approaches have demonstrated promising denoising performance on natural/synthetic images. This study tailors a neural network model for (ultra-)low-dose CT denoising, and assesses its performance in enhancing CT image quality and emphysema quantification. METHODS: The noise statistics in low-dose CT images has its unique characteristics and differs from that used in general denoising models. In this study, we first simulate the paired ultra-low-dose and targeted high-quality image of reference, with a well-validated pipeline. These paired images are used to train a denoising convolutional neural network (DnCNN) with residual mapping. The performance of the DnCNN tailored to CT denoising (DnCNN-CT) is assessed over various dose reduction levels, with respect to both image quality and emphysema scoring quantification. The possible over-smoothing behavior of DnCNN and its impact on different subcohort of patients are also investigated. RESULTS: Performance evaluation results showed that DnCNN-CT provided significant image quality enhancement, especially for very-low-dose level. With DnCNN-CT denoising on 3%-dose cases, the peak signal-to-noise ratio improved by 8 dB and the structure similarity index increased by 0.15. This outperformed the original DnCNN and the state-of-the-art nonlocal-mean-type denoising scheme. Emphysema mask was also investigated, where lung voxels of abnormally low attenuation coefficient were marked as potential emphysema. Emphysema mask generated after DnCNN-CT denoising on 3%-dose image was demonstrated to agree well with that from the full-dose reference. Despite over-smoothing in DnCNN denoising, which contributed to slight underestimation of emphysema score compared to the reference, such minor overcorrection did not affect clinical conclusions. The proposed method provided effective detection for cases with appreciable emphysema while serving as a reasonable correction for normal cases without emphysema. CONCLUSIONS: This work provides a tailored DnCNN for (ultra-)low-dose CT denoising, and demonstrates significant improvement on both the image quality and the clinical emphysema quantification accuracy over various dose levels. The clinical conclusion of emphysema obtained from the denoised low-dose images agrees well with that from the full-dose ones.

14.
Exp Cell Res ; 382(1): 111457, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175853

RESUMO

Chronic pancreatitis (CP) is a progressive, irreversible inflammatory and fibrotic disease. The characteristics of this disease are progressive inflammation, acinar atrophy and fibrosis. Numerous factors are involved in CP such as inflammation, and oxidative stress. Recently, it has been noted that fibroblast growth factor 21 (FGF-21) reduced the severity of acute pancreatitis in mice. However, whether FGF-21 has effects on CP remains unclear. Thus, the present study was undertaken to detect the effects of FGF-21 on l-arginine induced chronic pancreatitis/islet fibrosis in mice. We used l-arginine to create a CP model in C57BL/6 mice and treated these mice with FGF-21. Compared to normal mice, blood glucose and intra-peritoneal glucose tolerance test (IPGTT) revealed significant impairment in CP animal model. CP mice also had acinar atrophy, loss of pancreas morphology, inflammatory cells infiltration, extensive deposition of collagen, elevated -SMA expression, collagen I expression, serum amylase activity, MPO activity and MDA level. All these pathological changes were significantly improved by FGF-21 treatment. Moreover, FGF-21 ameliorated inflammatory state in the serum, pancreas and peritoneal macrophages of CP mice. Furthermore, we also found that FGF-21 could regulate differentiation of macrophages so as to improve pancreatic fibrogenesis in CP mice. Taken together, our study identifies the beneficial role of FGF-21 in CP and suggests that FGF-21 improves pancreatic fibrogenesis in CP via the mTOR pathway.

15.
Phytother Res ; 33(8): 2034-2043, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197891

RESUMO

Mast cells play an essential role in IgE-FcεR1-mediated allergic diseases. Citrus aurantium is a prolific source of flavonoids with various biological activities, including anti-inflammatory, antioxidant, and anti-tumor efficacies. Neohesperidin is a novel flavonoid isolated from the leaves of C. aurantium. In this study, the anti-allergic and anti-inflammatory potentials of neohesperidin were investigated along with its molecular mechanism. The anti-anaphylactic activity of neohesperidin was evaluated through hind paw extravasation study in mice. Calcium imaging was used to assess intracellular Ca2+ mobilization. The levels of cytokines and chemokines were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. Neohesperidin suppressed IgE-induced mast cell activations, including degranulation and secretion of cytokines and eicosanoids through inhibiting phosphorylation of Lyn kinase. Neohesperidin inhibited the release of histamine and other proinflammatory cytokines through a mast cell-dependent passive cutaneous anaphylaxis animal model. Histological studies demonstrated that neohesperidin substantially inhibited IgE-induced cellular infiltration and attenuated mast cell activation in skin tissue. In conclusion, our study revealed that neohesperidin could inhibit allergic responses in vivo and in vitro, and the molecule may be regarded as a novel agent for preventing mast cell-immediate and delayed allergic diseases.

16.
J Agric Food Chem ; 67(27): 7694-7705, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31250637

RESUMO

Liver plays a central role in modulating blood glucose level. Our most recent findings suggested that supplementation with microbiota metabolite sodium butyrate (NaB) could ameliorate progression of type 2 diabetes mellitus (T2DM) and decrease blood HbA1c in db/db mice. To further investigate the role of butyrate in homeostasis of blood glucose and glycogen metabolism, we carried out the present study. In db/db mice, we found significant hypertrophy and steatosis in hepatic lobules accompanied by reduced glycogen storage, and expression of GPR43 was significantly decreased by 59.38 ± 3.33%; NaB administration significantly increased NaB receptor G-protein coupled receptor 43 (GPR43) level and increased glycogen storage in both mice and HepG2 cells. Glucose transporter 2 (GLUT2) and sodium-glucose cotransporter 1 (SGLT1) on cell membrane were upregulated by NaB. The activation of intracellular signaling Protein kinase B (PKB), also known as AKT, was inhibited while glycogen synthase kinase 3 (GSK3) was activated by NaB in both in vivo and in vitro studies. The present study demonstrated that microbiota metabolite NaB possessed beneficial effects on preserving blood glucose homeostasis by promoting glycogen metabolism in liver cells, and the GPR43-AKT-GSK3 signaling pathway should contribute to this effect.


Assuntos
Ácido Butírico/administração & dosagem , Diabetes Mellitus Tipo 2/metabolismo , Glicogênio Hepático/metabolismo , Animais , Glicemia/análise , Ácido Butírico/metabolismo , Imunofluorescência , Microbioma Gastrointestinal/fisiologia , Transportador de Glucose Tipo 2/análise , Hemoglobina A Glicada/análise , Quinase 3 da Glicogênio Sintase/metabolismo , Células Hep G2 , Homeostase/efeitos dos fármacos , Humanos , Fígado/química , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas-G/análise , Transdução de Sinais/efeitos dos fármacos , Transportador 1 de Glucose-Sódio/análise
17.
J Transl Med ; 17(1): 204, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215436

RESUMO

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of early diagnosis and prediction for acute kidney injury (AKI). However, the current program for NGAL detection is not extensively applied in clinics due to the high expense of antibodies. Nucleic acid aptamers are single-strand DNAs or RNAs which could bind to targets with high specificity and affinity, and they have been widely used in the diagnosis and therapy for multiple diseases. It is valuable for us to develop a new method for NGAL detection using aptamers instead of antibodies to achieve increased efficiency and decreased cost. METHODS: Nucleic acid aptamers against NGAL were obtained after SELEX process using magnetic beads, and an enzyme-linked aptamer analysis (ELAA), which can be widely used in clinical diagnosis at low cost, were successfully established. The feasibility of ELAA was further validated with urine samples harvested from 43 AKI patients and 30 healthy people. RESULTS: Three candidate aptamers, including NA36, NA42 and NA53, were obtained after 8 rounds of SELEX process with magnetic beads and verified by quantitative polymerase chain reaction (qPCR), and the Kd value of each aptamer was 43.59, 66.55 and 32.52 nM, respectively. Moreover, the linear relationship was consistent at the range of 125-4000 ng/mL, and the detection limit of ELAA assay was 30.45 ng/mL. We also found that NGAL could be exclusively detected with NA53, and no cross-reaction between NA53 and human albumin or globulin occurred, the coefficient of variation (CV) between inner-plate and inter-plate was less than 15%, and the recovery rate was between 80 and 110%. Moreover, the sensitivity and specificity of ELAA assay in this study are 100% and 90%, respectively. Consistently, these results could also diagnose whether the occurrence of AKI in lots of patients, which has been demonstrated with the ELAA method we established after using NA53. CONCLUSIONS: Taken together, NA53, the best candidate aptamer targeting NGAL protein, can be applied in clinical testing.

18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(4): 333-338, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31167693

RESUMO

Objective To obtain the expression vector, which could be used for screening peptide drug against human immunodeficiency virus type 1 (HIV-1) integrase (IN) with bimolecular fluorescence complementation (BiFc). Methods Full-length IN sequence was amplified using high-fidelity PCR with the template pMDL vector, following with the insertion of target sequence into pBiFc-VN173 vector. Moreover, the recombinant vector pBiFc-VN173-IN was further confirmed by double enzyme digestion and sequencing. Compared with empty control, expression of IN from pBiFc-VN173-IN in HEK293T cells was validated by Western blotting and immunofluorescence assay (IFA). Results The pBiFc-VN173-IN vector, which could drive the ectopic expression of IN, was successfully obtained through high-fidelity PCR, vector construction and confirmation. In addition, Western blot analysis and IFA validated the ectopic expression of IN in HEK293T cells after transfection. Conclusion The pBiFc-VN173-IN vector has been successfully obtained, and it will be helpful for screening specific peptides against IN using BiFc.


Assuntos
Vetores Genéticos , Inibidores de Integrase de HIV/farmacologia , HIV-1 , Peptídeos/farmacologia , Western Blotting , Células HEK293 , Integrase de HIV , Humanos , Transfecção
19.
J Epidemiol Community Health ; 73(9): 796-801, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31227586

RESUMO

BACKGROUND: Past studies have found a strong relationship between alcohol drinking and human health. METHODS: In this study, we first tested the association of rs671 with alcohol use in 2349 participants in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis. RESULTS: We found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship. CONCLUSIONS: Compared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.

20.
ACS Appl Mater Interfaces ; 11(23): 20828-20837, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31117448

RESUMO

It is of critical importance to exploit high-performance phase-change materials (PCM) for thermal energy storage. Present form-stable PCM suffer from the defects in low PCM loading, poor form stability, low thermal conductivity, and complicated approaches. We prepared a novel microtubule-encapsulated phase-change material (MTPCM) by encapsulating lauric acid (LA) into kapok fiber (KF) microtubules that had been precoated with silver nanoparticles. The measured melting and freezing temperatures were 43.9 and 41.3 °C for the LA/KF MTPCM and 44.1 and 42.1 °C for the LA/KF@Ag MTPCM, respectively. After being heated, the MTPCM can retain its original solid state without leaking, even under a pressure of 500 times the gravity of MTPCM itself, which shows that the encapsulated phase-change material can undergo a solid-liquid transition microscopically while retaining its macroscopic solid state. The latent heats of fusion were found to be 153.5 J/g for the LA/KF MTPCM and 146.8 J/g for the LA/KF@Ag MTPCM, which is up to 86.5% and 82.7% that of pristine LA, respectively. This thermal energy storage capacity is much higher than reported values in recent literature, which tend to be ≤60%. In contrast with the penalty of a 3.8% decrease in latent heat capacity, the remarkable 92.3% increase in thermal conductivity caused by the introduction of silver nanoparticles is more pronounced. The thermoregulatory capacity analysis results show that the thermal transfer efficiency of LA/KF@Ag MTPCM has been enhanced significantly by 15.8% and 23.5% in terms of thermal energy storage and release compared to that of the LA/KF MTPCM. Moreover, the LA/KF@Ag MTPCM exhibits a robust thermal, chemical, and morphological reliability after 2000 thermal cycles, which makes it favorable for repetitive thermal energy storage/retrieval applications. The high latent heat, suitable phase-change temperature, outstanding form stability, robust thermal reliability, enhanced thermal transfer efficiency, and the inherited advantages of KF and nanosilver provide potential for the novel application of MTPCM in solar thermal energy storage, waste heat recovery, intelligent thermoregulated textiles, and infrared stealth of important military targets.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA