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1.
J Diabetes Res ; 2020: 2308520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185234

RESUMO

Cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) overexpression results in endothelial apoptosis, thus mediating vascular endothelial injury in hyperglycaemia. E26 transformation-specific sequence transcription factor-1 (ESE-1), which belongs to the E26 transformation-specific family of transcription factors, has been demonstrated to be involved in COX2 and iNOS gene transcription. Our previous study indicated that SET domain-containing protein 8 (SETD8) downregulation is involved in high glucose-mediated endothelial inflammation in human umbilical vein endothelial cells (HUVECs). Here, we report that SETD8 plays a major role in hyperglycaemia-induced COX2 and iNOS expression. In HUVECs, upregulation of ESE-1 expression was related to high glucose-mediated apoptosis and COX2 and iNOS expression. High glucose inhibited SETD8 expression, and overexpression of SETD8 diminished the effects of high glucose treatment. Consistently, RNA silencing of SETD8 led to the opposite effect. Furthermore, SETD8 was found to interact with specificity protein 1 (SP1). Blockade of SP1 protected against high glucose-mediated endothelial injury. Mechanistically, we showed that H4K20me1, a downstream target of SETD8, and SP1 were enriched at the ESE-1 promoter region by ChIP assay. Luciferase reporter assays indicated that SETD8 overexpression attenuated ESE-1 promoter activity and augmented the inhibitory effect of siSP1 on ESE-1 promoter activity. In general, our data indicate that SETD8 interacts with SP1 to coregulate ESE-1 expression, which is involved in hyperglycaemia-mediated endothelial apoptosis in HUVECs.

2.
Int J Biol Sci ; 16(7): 1166-1179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174792

RESUMO

Carbon tetrachloride (CCl4), Concanavalin A (ConA), bile duct ligation (BDL), and liver resection (LR) are four types of commonly used mouse models of acute liver injury. However, these four models belong to different types of liver cell damage while their application situations are often confounded. In addition, the systematic changes of multiple extra-liver organs after acute liver injury and the crosstalk between liver and extra-liver organs remain unclear. Here, we aim to map the morphological, metabolomic and transcriptomic changes systematically after acute liver injury and search for the potential crosstalk between the liver and the extra-liver organs. Significant changes of transcriptome were observed in multiple extra-liver organs after different types of acute liver injury despite dramatic morphological damage only occurred in lung tissues of the ConA/BDL models and spleen tissues in the ConA model. Liver transcriptomic changes initiated the serum metabolomic alterations which correlated to transcriptomic variation in lung, kidney, and brain tissues of BDL and LR models. The potential crosstalk might lead to pulmonary damage and development of hepatorenal syndrome (HRS) and hepatic encephalopathy (HE) during liver injury. Serum derived from acute liver injury mice damaged alveolar epithelial cells and human podocytes in vitro. Our data indicated that different types of acute liver injury led to different transcriptomic changes within extra-liver organs. Integration of serum metabolomics and transcriptomics from multiple tissues can improve our understanding of acute liver injury and its effect on the other organs.

3.
Clin Biochem ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32197940

RESUMO

BACKGROUND: Given that both insufficient and excess maternal iodine have adverse consequences such as poor cognitive performance, delayed physical development and increased fetal and infant mortality, the determination of maternal iodine status is very important. In this study, we established and verified a method involving inductively coupled plasma-mass spectrometry (ICP-MS) technology for the rapid determination of the amniotic fluid iodine concentration (AFIC), breast milk iodine concentration (BMIC) and cerebrospinal fluid (CSF) iodine concentration (CSFIC). METHOD: Amniotic fluid, breast milk and CSF were collected from residual samples at Peking Union Medical College Hospital (PUMCH). The linearity, detection limit, precision, recovery, carryover and matrix effect of the testing method using ICP-MS technology were thoroughly evaluated according to the EP-10-A2 evaluation protocol approved by the Clinical and Laboratory Standards Institute (CLSI) guidelines. Furthermore, we evaluated the AFIC, BMIC and CSFIC distributions among clinical patients from PUMCH. RESULTS: The correlation coefficient (r) was higher than 0.99 (0.995-1.000). The limit of detection (LOD) was 0.233 µg/L, and the limit of quantification (LOQ) was 0.778 µg/L. For amniotic fluid, breast milk and CSF, the assay repeatabilities were 1.5%-1.8%, 1.9%-4.0% and 1.8%-4.0%, respectively, and the within-laboratory coefficient of variations (CV%) over five days were 3.3%-9.2%, 7.2%-8.0% and 3.2%-7.8%, respectively. The recovery rates ranged from 97.7% to 109.8%. Moreover, the median concentrations of iodine in the amniotic fluid, breast milk and CSF of the patients from PUMCH were 176.3 µg/L, 136.0 µg/L, and 81.8 µg/L, respectively. CONCLUSION: A rapid, stable and accurate method that incorporates ICP-MS technology for the determination of iodine concentration was established for amniotic fluid, breast milk and CSF in this study.

4.
Br J Ophthalmol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075819

RESUMO

AIM: To reassess the association between near work, outdoor exposure and myopia in children through an objective approach. METHODS: Eighty-six children (10.13±0.48 years) were asked to wear Clouclip, a newly developed wearable device that is able to measure working distance and eye-level illuminance, for a complete week to obtain information on near work and outdoor exposure. The mean daily Clouclip wearing time was 11.72±1.14 hour. The spherical equivalent refraction was determined by cycloplegic autorefraction. RESULTS: The myopic children were found to be exposed to light intensities >3000 lux (0.68±0.50 hour vs 1.02±0.53 hour, p=0.012) and >5000 lux (0.42±0.35 hour vs 0.63±0.31 hour, p=0.004) for shorter durations on average each day than the non-myopic children. Additionally, the myopic children spent more time on average each day on activities at a distance of <20 cm than non-myopic children (1.89±0.61 hour vs 1.52±0.77 hour, p=0.019). In the multivariate logistic analysis, the time spent with a higher light intensity (>3000 lux (OR=0.27, 95% CI: 0.10 to 0.72, p=0.009); >5000 lux (OR=0.11, 95% CI: 0.02 to 0.56, p=0.008)) and a working distance of <20 cm (in a circumstance of >3000 lux (OR=1.17, 95% CI: 1.09 to 1.86, p=0.038) or in that of >5000 lux (OR=1.12, 95% CI: 1.03 to 1.77, p=0.046)) were the independent protective factors and risk factors, respectively. CONCLUSION: The current study provides novel evidence, based on objective data, to support the association between the intensity of near work, light intensity and myopia. However, the causality and the dose-effect relationship need to be investigated further.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32013027

RESUMO

Remediation of soil heavy metal by biochar has been extensively studied. However, few studies focused on the role of biochar on the co-immobilization of cadmium (Cd(II)) and arsenate (As(V)) and related soil nutrient availability. Remediation tests were conducted with three types of pristine and ferric trichloride (FeCl3) modified biochar (rice, wheat, and corn straw biochar) in Cd-As co-contaminated soil, with application rates of 1, 5, and 10% (w/w) and the incubation of 1, 7, 10, and 15 days. Using TCLP (Toxicity Characteristic Leaching Procedure) method, 10% of FeCl3 modified corn-straw derived biochar (FCB) had the highest immobilization efficiency of Cd(II) (63.21%) and As(V) (95.10%) after 10 days of the incubation. Iron-modified biochar immobilized higher fractions of water-soluble (F1) and surface-absorbed (F2) metal fractions than pristine biochar. For FCB amendment, Cd was mostly presented in the organic matter (OM) and sulfides associated (F4) and residual (F5) fractions (88.52%), as was found in the Fe-Al (oxides and hydroxides) (F3), F4, and F5 fractions (75.87%). FCB amendment increased soil pH values and available iron contents (p < 0.05), while no changes in soil available phosphorus content (p > 0.05). This study showed that FCB application reduces the environmental mobility of metals in Cd-As contaminated soil, while it also increases soil pH and available nutrient mobility, improving soil environmental quality and reducing remediation costs.

6.
J Mol Med (Berl) ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32036390

RESUMO

Progressive tubulointerstitial fibrosis is the common final outcome for all kidney diseases evolving into chronic kidney disease (CKD), whereas molecular mechanisms driving fibrogenesis remain elusive. Retinoic acid-inducible gene-I (RIG-I), an intracellular pattern recognition receptor, is originally identified participating in immune response by recognizing virus RNA. Here, we revealed for the first time that RIG-I was induced in unilateral ureteral obstruction (UUO) and folic acid (FA) renal fibrosis models and moderate-degree renal fibrosis patients. Besides, we found RIG-I was mainly located in renal tubular epithelial cells and promoted the production and release of inflammatory cytokines, such as interleukin (IL)-1ß and IL-6 through activation of NF-κB. Inflammatory cytokines released by tubular epithelial cells activated c-Myc-mediated TGF-ß/Smad signaling in fibroblasts, which in turn aggravated interstitial fibrosis by promoting fibroblast activation and production of extracellular matrix components (ECM). Deficiency of RIG-I attenuated renal fibrosis by the regulation of inflammatory responses, c-Myc expression, and fibroblast activation. Besides, gene silencing of RIG-I reduced inflammatory cytokines in cultured tubular epithelial cells treated with Angiotensin II. Knockdown of c-Myc or c-Myc inhibitor blocked IL-1ß-induced fibroblast activation. Collectively, our study demonstrates that RIG-I plays a significant role in the progress of renal fibrosis via regulating c-Myc-mediated fibroblast activation. KEY MESSAGES: • RIG-I was constantly elevated in kidneys from renal fibrotic mice. • RIG-I facilitated inflammatory cytokine production in tubular epithelial cells. • RIG-I aggravated renal fibrosis via c-Myc-mediated TGF-ß/Smad activation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32043861

RESUMO

The self-assembled gold nanoparticle (NP) superlattice displays unusual but distinctive features such as high mechanical and free-standing performance, electrical conductivity, and plasmonic properties, which are widely employed in various applications especially in biological diagnostics and optoelectronic devices. For a two-dimensional (2D) superlattice monolayer film composed of a given metal nanostructure, it is rather challenging to tune either its plasmonic properties or its optical properties in a reversible way, and it has not been reported. It is therefore of significant value to construct a free-standing 2D superlattice monolayer film of gold nanoparticles with an intelligent response and desired functions. Herein, we developed an easy and efficient approach to construct a gold nanoparticle superlattice film with a dual-responsive plasmonic switch. In this system, gold nanoparticles were coated by polyaniline (PANI) and then interracially self-assembled into a monolayer film at the air-liquid interface. The PANI shell plays two important roles in the superlattice monolayer film. First, the PANI shell acts as a physical spacer to provide a steric hindrance to counteract the van der Waals (vdW) attraction between densely packed nanoparticles (NPs), resulting in the formation of a superlattice by adjusting the thickness of the PANI shell. Second, the PANI shells provide the superlattice film with multiple stimuli such as electrical potential and pH change, leading to reversible optical and plasmonic responsiveness. The superlattice monolayer film can show a vivid color change from olive green to pink, or from olive green to violet by the change of the corresponding stimuli. Also, the localized surface plasmonic resonance (LSPR) of the superlattice monolayer film can be reversibly modulated by both by changing the local pH and applying an electric potential. Notably, a significant plasmonic shift of 157 nm can be achieved in the superlattice monolayer film when the PANI shell with a thickness of 35 nm and gold nanorods as a core were used. The superlattice monolayer film with dual-responsive plasmonic switches is promising for a range of potential applications in optoelectronic devices, plasmonic and colorimetric sensors, and surface-enhanced Raman scattering (SERS).

8.
J Healthc Eng ; 2020: 5834532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015796

RESUMO

Private sector participation in the healthcare market via public-private partnership (PPP) could be considered an available approach to narrow down the medical resource gap and improve the operational efficiency of healthcare facilities. Accordingly, this study aims to examine the influence and relative importance among critical factors for the intention and behaviour of the private sector towards participation in Chinese healthcare market (CHM) via PPP. We defined five hypotheses from previous literature and built a theoretical model based on modified theory of planned behaviour. Then, covariance-based structural equation modelling was applied to analyse the questionnaires provided by 248 respondents from construction companies, real estate developers, pharmaceutical companies, private hospitals, asset management companies, and medical industry property investment companies in China. Results indicated that attitude towards behaviour (ß = 0.466, P < 0.001), subjective norm (ß = 0.167, P < 0.05), perceived behavioural control (ß = 0.231, P < 0.01), and facilitating conditions (ß = 0.305, P < 0.001) are positively significant to behavioural intention; behavioural intention also shows a strong linkage with behaviour (ß = 0.931, P < 0.001). Findings provide reference for governments and public authorities to exert additional efforts in implementing appropriate measures that will stimulate the private sector's motivation to participate in CHM via PPP.

9.
J Xray Sci Technol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32083610

RESUMO

OBJECTIVE: To investigate the measurement reproducibility of the maximum diameter on MRI routine sequence (T1WI, T2WI, DWI) and CT in peripheral and central lung cancer, and to provide reference standard for evaluating treatment responses for lung cancer. METHODS: 53 patients with lung cancer underwent CT and 3.0T MR scanning. The maximum diameter was measured according to the RECIST1.1 standard on images of CT (lung and enhanced mediastinal window), MRI T2-BLADE, axial T1-VIBE and DWIb0, DWIb300, DWIb800, respectively. The reproducibility of the diameters was analyzed with intraclass correlation coefficient (ICC), and the distribution of measurement points with the Bland-Altman method. The difference analysis was assessed by paired samples t-test and nonparametric rank sum test, P < 0.05 is considered statistically significant. RESULTS: Reproducibility of diameters derived from routine MRI and CT was good (ICC > 0.75). For peripheral lung cancer, there was no significant difference in diameters between CT and MRI. While for central lung cancer, there was significant difference in diameters measured between using CT and each MRI sequence. However, the diameters derived from T1-VIBE and T2-BLADE were not significantly different from all DWI sequences. CONCLUSIONS: For peripheral lung cancer, the measurement on CT and routine MRI sequences can potentially replace each other after comprehensive consideration of examination purposes, but for central lung cancer, alternative use of CT and MRI in evaluating treatment responses for lung cancer should needs extra attention. The diameter measurement of lung cancer on DWI is consistent with that on T1WI and T2WI, suggesting that DWI can provide functional and morphological information.

10.
Rev Esp Enferm Dig ; 112(3): 201-210, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32022577

RESUMO

INTRODUCTION: hepatocellular carcinoma (HCC) recurrence after liver resection remains a major threat for patients' survival. Sorafenib is recommended as an adjuvant treatment for patients after a liver resection. The objective of this meta-analysis was to estimate the therapeutic value of sorafenib in patients who underwent a HCC resection. MATERIALS AND METHODS: relevant reports were retrieved from electronic databases. All eligible studies were carefully reviewed and the required data were extracted. Outcome with regard to overall survival (OS), recurrence-free survival (RFS), recurrence rate, mortality rate, OS time (months) and RFS time (months) were analyzed. RESULTS: nine trials were included. The results of the meta-analysis revealed that sorafenib did not exert a significant superior effect on OS (sorafenib as reference: hazard ratio [HR] = 2.15; 95% CI, 0.91-5.08, p = 0.80; control as reference: HR = 0.56; 95% CI, 0.31-1.02; p = 0.059), OS time in months (weighted mean differences [WMD] = 4.96; 95% CI, -1.21-11.13; p = 0.115) and RFS time in months (WMD = 7.58; 95% CI, -1.36-16.53; p = 0.097). Nevertheless, the use of sorafenib was associated with a significantly higher RFS (HR = 0.53; 95% CI, 0.31-0.90; p = 0.018), and a lower recurrence rate (risk ratio [RR] = 0.72; 95% CI, 0.60-0.86; p < 0.001) and mortality rate (RR = 0.74; 95% CI, 0.57-0.95; p = 0.20). CONCLUSION: according to the present meta-analysis, sorafenib showed a significant benefit in RFS, recurrence rate and mortality rate. The effect of sorafenib for the prevention of HCC recurrence seems to be encouraging. However, more evidence is still needed before reaching a definitive conclusion.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32068900

RESUMO

Glycerophospholipids (GPs) and sphingolipids (SPs) are important lipid components in the body and play biological functions. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are important nutrients, and their supplements are commonly used for preventing some diseases. However, the effect of n-3 PUFAs on the human glycerophospholipidome and sphingolipidome is unclear. We used targeted lipidomics to study the GP and SP profile of healthy individuals after supplementation with n-3 PUFAs for 3, 7, 14 and 21 days. Fuzzy c-means clustering was used to cluster the lipid species into six classes reflecting different changed-content patterns after n-3 PUFA supplementation. Among the species with significantly changed content, lysophospholipids were the most sensitive; their content started to increase on day 3. The content of phosphatidylserines increased at a later stage. The content of most of the phosphatidylcholines and alkylphosphatidylcholines decreased on day 21. A correlation network analysis of lipid species suggested that some enzymes involved in the metabolism of lysophospholipids and phosphatidylserines were regulated by n-3 PUFAs. Levels of creatine kinase-MB (CK-MB), urea, glucose, triglycerides and total bilirubin were altered by n-3 PUFA at 21 days. Correlation analysis revealed that the level of CK-MB was negatively correlated with those of species in lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and phosphatidylserine classes, which were increased by n-3 PUFA supplementation. With the analysis in this work, we demonstrated the regular pattern of n-3 PUFAs on GP and SP metabolism, which provides a pharmacological basis for n-3 PUFAs for clinical application.

12.
Cell Cycle ; 19(3): 290-299, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31914881

RESUMO

We aimed to identify potential mechanism associated with acute kidney injury (AKI) after kidney transplantation. The dataset GSE53771, which contained 18 zero-hour (ZERO group) and 18 selected post-transplant (POST group) biopsy samples from 18 kidney allografts (8 AKI and 10 controls) was downloaded from GEO database. Differentially expressed miRNAs (DEMIs) were screened using limma package, and bidirectional hierarchical clustering of the DEMIs was performed using the pheatmap package. Target genes of DEMIs were predicted by miRWalk 2.0, miRNA-target genes networks were presented using Cytoscape, protein-protein interaction (PPI) networks were constructed by STRING (version:10.0) database, and competing endogenous RNAs (ceRNA) regulating network were constructed using Cytoscape. In ZERO and POST groups, a total of 4 and 24 differentially expressed miRNAs were obtained in AKI samples compared with control, respectively. Specifically, 71 lncRNAs were obtained to interact with five miRNAs (hsa-miR-215-5p, hsa-miR-192-5p, hsa-miR-422a, hsa-miR-212-3p and hsa-miR-122-5p). Histone chaperone ASF1A (ASF1A) and bromodomain and WD repeat-containing protein 1(BRWD1) were targeted by hsa-miR-212-3p in PPI network. In ceRNA network, lncRNA XIST could interact with four miRNAs (hsa-miR-212-3p, hsa-miR-122-5p, hsa-miR-215-5p, and hsa-miR-192-5p). LncRNA XIST might serve as a ceRNA to sponge hsa-miR-212-3p to regulate the development of AKI via altering the expression of ASF1A/BRWD1. Furthermore, lncRNA XIST could also interact with hsa-miR-122-5p to modulate the expression of PFKFB2 in thyroid hormone signaling pathway and AMPK signaling pathway. LncRNA XIST can serve as a ceRNA to sponge hsa-miR-212-3p and hsa-miR-122-5p to regulate AKI progression via modulating the expression of ASF1A, BRWD1, and PFKFB2.[Figure: see text].

13.
Front Med ; 14(1): 51-59, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31938981

RESUMO

The aim of this study was to characterize rpoC gene mutations in Mycobacterium tuberculosis (MTB) and investigate the factors associated with rpoC mutations and the relation between rpoC mutations and tuberculosis (TB) transmission. A total of 245 MTB clinical isolates from patients with TB in six provinces and two municipalities in China were characterized based on gene mutations through DNA sequencing of rpoC and rpoB genes, phenotyping via standard drug susceptibility testing, and genotypic profiling by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. Approximately 36.4% of the rifampin-resistant isolates harbored nonsynonymous mutations in the rpoC gene. Twenty-nine nonsynonymous single mutations and three double mutations were identified. The rpoC mutations at locus 483 (11.3%) were predominant, and the mutations at V483G, W484G, I491V, L516P, L566R, N698K, and A788E accounted for 54.5% of the total detected mutations. Fifteen new mutations in the rpoC gene were identified. Rifampin resistance and rpoB mutations at locus 531 were significantly associated with rpoC mutations. MIRU-VNTR genotype results indicated that 18.4% of the studied isolates were clustered, and the rpoC mutations were not significantly associated with MIRU-VNTR clusters. A large proportion of rpoC mutation was observed in the rifampicin-resistant MTB isolates. However, the findings of this study do not support the association of rpoC mutation with compensated transmissibility.

14.
Int J Oral Maxillofac Implants ; 35(1): 167-177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923299

RESUMO

PURPOSE: To identify whether or not immediate loading yields different clinical outcomes from conventional loading of single-tooth implants in the esthetic zone. MATERIALS AND METHODS: Various databases (MEDLINE/PubMed, Cochrane [CENTRAL], and Embase) were searched electronically to find articles published in the English language from January 2000 to April 2018. Only randomized controlled clinical trials (RCTs) that compared conventional and immediate implant loading with a minimum follow-up period of 1 year or more were considered. Available data were pooled for meta-analysis using the Review Manager software. RESULTS: Seven RCTs were included. There was no significant difference between immediate and conventional loading protocols on implant survival at the 1-year follow-up (risk ratio [RR] = 0.99; 95% confidence interval [CI]: 0.95 to 1.02). The differences regarding marginal bone loss between the two protocols were statistically insignificant (mean difference [MD] = 0.03 mm; 95% CI: -0.09 to 0.15 mm at the 1-year follow-up, and MD = -0.01 mm; 95% CI: -0.16 to 0.15 mm at the 2-year follow-up). Soft tissue changes following different loading protocols revealed no significant differences in the mesial papillae (MD = 0.30 mm; 95% CI: -0.25 to 0.85 mm), the distal papillae (MD = -0.00 mm; 95% CI: -0.42 to 0.42 mm), and the midfacial mucosa (MD = -0.33 mm; 95% CI: -1.17 to 0.50 mm) at the 1-year follow-up. The esthetic outcomes and patient satisfaction were reported in two and three RCTs, respectively. CONCLUSION: A short-term follow-up of single-tooth implants in the esthetic zone showed that the loading protocols (conventional or immediate loading) are not likely to influence the clinical outcomes, including implant survival and peri-implant stability of soft and hard tissues.


Assuntos
Implantes Dentários para Um Único Dente , Carga Imediata em Implante Dentário , Implantação Dentária Endo-Óssea , Estética Dentária , Humanos , Satisfação do Paciente
15.
J Exp Clin Cancer Res ; 39(1): 22, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992334

RESUMO

BACKGROUND: The mechanism underlying sorafenib resistance in hepatocellular carcinoma (HCC) remains unclear. Accumulating evidence suggests that tumor-initiating cells (TICs) are a pivotal driving force. Both CD44 and Hedgehog signaling play crucial roles in TIC properties in HCC. In this study, we explored the roles of CD44 and Hedgehog signaling in sorafenib resistance and evaluated the therapeutic effect of cotreatment with sorafenib and Hedgehog signaling inhibitors in HCC patient-derived organoid (PDO) models to improve treatment efficacy. METHODS: We collected HCC specimens to establish PDO models. Cell viability and malignant transformation properties were investigated after treatment with different TIC-related inhibitors alone or in combination with sorafenib to evaluate the therapeutic effect in PDOs and cell lines by in vitro and in vivo experiments. Expression levels of Hedgehog signaling proteins and CD44 were monitored to reveal potential relationships. RESULTS: We demonstrated that our HCC PDO models strongly maintained the histological features of the corresponding tumors and responded to drug treatment. Furthermore, CD44-positive HCC PDOs were obviously resistant to sorafenib, and sorafenib increased CD44 levels. A drug screen showed that compared with Notch, Hippo and Wnt signaling inhibitors, a Hedgehog signaling inhibitor (GANT61) potently suppressed HCC PDO cell viability. In addition, there was a highly synergistic effect in vitro and in vivo on the suppression of cell viability and malignant properties when sorafenib and GANT61 were added to CD44-positive HCC PDOs and cell lines, respectively. Furthermore, the upregulation of CD44 and Hedgehog signaling induced by sorafenib was reversed by GANT61. CONCLUSIONS: GANT61 significantly suppressed Hedgehog signaling to reverse sorafenib resistance in CD44-positive HCC. The combination of sorafenib and Hedgehog signaling inhibitors might be effective in HCC patients with high CD44 levels as a personalized-medicine approach.

16.
Langmuir ; 36(1): 250-256, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31697894

RESUMO

Large scaled two-dimensional free-standing monolayer films of gold nanoparticles show distinctive optical, electrical, and chem-physical propertie making them a new class of advanced plasmonic materials differing from bulk materials and individual nanoparticles in solution. The conventional 2D gold nanoparticle films usually possess symmetric structures and identical properties of gold nanoparticles on both sides. Herein, we developed an easy and efficient approach to construct a new type of free-standing 2D gold nanoparticle monolayer film with asymmetric gold nanoparticle structures and functions, called a 2D Janus gold nanoparticle film. The remarkable feature of our method is the subsequent asymmetric growth on one side of the interfacial self-assembled gold nanoparticle monolayer film at the air-liquid interface. It is very easy to control the morphology of the Janus film by simply and precisely adjusting the size and shape of the gold nanoparticles on the top side, and selectively tuning the structure and composition on the bottom side of the film by growing gold nanoparticles or other noble metals such as Ag, Pt, and Pd. Unlike the conventionally prepared Janus films at solid substrate that require long-time etching and transfer procedures, other features of our method include the short time in which the interfacial self-assembly and the subsequent asymmetric growth are completed as well as the easily transferable property of the Janus film onto different substrates, such as quartz glass sheets, silicon wafers, and PDMS. The obtained Janus gold nanoparticle film shows asymmetric wettabilities, optical properties, and surface-enhanced Raman scattering (SERS) effects, which is promising for a range of potential applications in optical devices, sensors, and asymmetric catalysis.

17.
Infection ; 48(1): 109-116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31677085

RESUMO

BACKGROUND: Inappropriate initial antimicrobial therapy (IIAT) may increase the mortality rate of hematological malignancies (HMs) patients with Gram-negative bacteria bloodstream infections (GN-BSI). The aim of this study is to determine whether IIAT affects the prognosis in this patient population and recommend the appropriate antibiotic regimen to minimize IIAT. METHODS: We reviewed a retrospective cohort study of 361 HM patients with neutropenic fever from GN-BSI. The patients' clinical characteristics and the results of the drug sensitivity test in vitro were analyzed. RESULTS: IIAT rate was 21.3% in HM patients with neutropenic fever caused by GN-BSI. There was a significant difference in 7-day mortality rate between patients treated with appropriate antibiotics and those with IIAT (7.7% vs 29.9%, p < 0.01). Multivariate analysis confirmed that IIAT was an independent risk factors for early mortality [4.860 (1.541-15.323)]. Drug sensitivity data of GN-bacteria suggested that carbapenems monotherapy or beta-lactamase inhibitors (BLBLI) combined with amikacin as the initial therapy can effectively reduce the IIAT rate. In the stratified antibiogram based on prior antimicrobial exposure, our results showed that BLBLI monotherapy could be initially used as an empirical treatment in patients without prior antimicrobial exposure. In those who had received prior antimicrobial exposure, BLBLI (especially piperacillin-tazobactam) combined with amikacin is recommended. CONCLUSIONS: IIAT was a critical factor contributing to the mortality of HM patients with neutropenic fever from GN-BSI.

18.
Immunol Invest ; 49(1-2): 15-31, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31298049

RESUMO

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology. Intercellular cell adhesion molecule-1 (ICAM-1) is critical for leukocyte adhesion to endothelium and migration out of blood vessels and thus participates in many autoimmune diseases. Previous studies of blood and urinary ICAM-1 in SLE have yielded inconsistent results.Methods: The following databases were searched for studies that compared blood and/or urinary ICAM-1 in SLE patients vs. healthy control subjects, and/or in SLE with active vs. inactive diseases: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Web of Science. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model when there was significant heterogeneity (assesses using the Cochrane Q test and I2 statistics), and using a fixed-effects model otherwise. Publication bias was assessed using funnel plot and egger text.Results: The initial screening yielded a total of 1,215 articles; 22 articles (14 reporting blood ICAM-1, 7 reporting urinary ICAM-1 and 1 reporting both) were included in the meta-analysis. In comparison to healthy controls, SLE patients had elevated urinary ICAM-1 (SMD: 0.711; 95% CI: 0.521, 0.901) as well as blood ICAM-1 (SMD: 0.725; 95% CI: 0.385, 1.065). Blood ICAM-1 did not differ significantly between active and inactive SLE (SMD: 0.396; 95% CI: -0.556, 1.347).Conclusion: Elevated blood and urinary ICAM-1 is a biomarker for SLE, but does not differentiate active and inactive SLE.

19.
Adv Mater ; 32(2): e1905517, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782563

RESUMO

Solid-state lithium-metal batteries with solid electrolytes are promising for next-generation energy-storage devices. However, it remains challenging to develop solid electrolytes that are both mechanically robust and strong against external mechanical load, due to the brittleness of ceramic electrolytes and the softness of polymer electrolytes. Herein, a nacre-inspired design of ceramic/polymer solid composite electrolytes with a "brick-and-mortar" microstructure is proposed. The nacre-like ceramic/polymer electrolyte (NCPE) simultaneously possesses a much higher fracture strain (1.1%) than pure ceramic electrolytes (0.13%) and a much larger ultimate flexural modulus (7.8 GPa) than pure polymer electrolytes (20 MPa). The electrochemical performance of NCPE is also much better than pure ceramic or polymer electrolytes, especially under mechanical load. A 5 × 5 cm2 pouch cell with LAGP/poly(ether-acrylate) NCPE exhibits stable cycling with a capacity retention of 95.6% over 100 cycles at room temperature, even undergoes a large point load of 10 N. In contrast, cells based on pure ceramic and pure polymer electrolyte show poor cycle life. The NCPE provides a new design for solid composite electrolyte and opens up new possibilities for future solid-state lithium-metal batteries and structural energy storage.

20.
J Affect Disord ; 260: 695-702, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31561112

RESUMO

OBJECTIVE: The aim of this study was to assess the association between serum growth differentiation factor-15(GDF-15) and 3-month depression after acute ischemic stroke. METHODS: In this single-center prospective study, patients with first-ever acute ischemic stroke between March 2017 and November 2018 were included. Neurological and neuropsychological evaluations were conducted during the 3-month follow-up. The predictive value of GDF-15 to predict the post-stroke depression (PSD) within 3 months, was compared with other known predictors. RESULTS: The median level of GDF-15 in 310 stroke patients was 1285(IQR, 846-1934) ng/l. During the 3-month follow-up, 76 patients were defined as depression (24.5%; 95% confidence interval [CI]: 17.9%-29.3%), and GDF-15 levels in those patients were nearly more than 1 time greater as compared with patients who were free of depression (P < 0.001). Using the ROC curves, GDF-15 serum level at 1660 ng/l predicted the PSD with the highest sensitivity and specificity [67.1% and 77.4%, respectively; AUC=0.78, 95%CI: 0.72-0.84; P < 0.001]. Interestingly, When GDF-15 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.81(0.029) to 0.88(0.020). A significant difference in the AUC between the established risk factors alone and the addition of GDF-15 was observed (difference, 0.07[0.009]; P = 0.001). In a multivariate model using the elevated levels of GDF-15 (≥cut-off=1660 ng/l) vs. normal (

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