Cholesterol is a structural component of the cell and is indispensable for normal cellular function, although its excess often leads to abnormal proliferation, migration, inflammatory responses ...and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (apoA-I) and the apoA-I-containing high-density lipoprotein (HDL). Maintaining efficient cholesterol efflux is essential for normal cellular function. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that apoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells to HDL and thereby regulates angiogenesis. AIBP- and HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 (also known as KDR) dimerization and signalling and inhibits vascular endothelial growth factor-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Notably, Aibp, a zebrafish homologue of human AIBP, regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell-autonomous regulator of angiogenesis. aibp knockdown results in dysregulated sprouting/branching angiogenesis, whereas forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1 (also known as Abca1a) Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1 Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from endothelial cells and that effective cholesterol efflux is critical for proper angiogenesis.
Digital droplet infusion Fang, Zecong; Li, Andrew I; Liu, Hong ...
Lab on a chip,
02/2021, Letnik:
21, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Infusion pumps have been widely used in clinical settings for the administration of medications and fluids. We present the digital droplet infusion (DDI) device, a low-cost, high-precision digital ...infusion system, utilizing a microfluidic discretization unit to convert continuous flow into precisely delivered droplet aliquots and a valving unit to control the duration and frequency of flow discretization. The DDI device relies on a distinct capillarity-dominated process of coalescence and pinch-off of droplets for flow digitization, which is monitored by a pair of conductive electrodes located before and after the junction. The digital feedback-controlled flow rate can be employed to adjust a solenoid valve for refined infusion management. With this unique digital microfluidic approach, the DDI technology enables a simple yet powerful infusion system with an ultrahigh resolution of digital droplet transfer volume, as small as 57 nL, which is three orders of magnitude lower than that of clinical standard infusion pumps, as well as a wide range of digitally adjustable infusion rates ranging from 0.1 mL h
to 10 mL h
, in addition to an array of programmable infusion profiles and safety features. Its modular design enables fast assembly using only off-the-shelf and 3D-printed components. Overall, benefiting from its simple device architecture and excellent infusion performance, the DDI technology has great potential to become the next-generation clinical standard for drug delivery with its high precision and ultimate portability at a low cost.
The chronic remitting and relapsing intestinal inflammation characteristic of Crohn's disease frequently leads to fibrosis and subsequent stenosis of the inflamed region. Approximately a third of all ...Crohn's disease patients require resection at some stage in their disease course. As the pathogenesis of Crohn's disease associated fibrosis is largely unknown, a strong necessity exists to better understand the pathophysiology thereof.
In this study, we investigated changes of the DNA methylome and transcriptome of ileum-derived fibroblasts associated to the occurrence of Crohn's disease associated fibrosis. Eighteen samples were included in a DNA methylation array and twenty-one samples were used for RNA sequencing.
Most differentially methylated regions and differentially expressed genes were observed when comparing stenotic with non-inflamed samples. By contrast, few differences were observed when comparing Crohn's disease with non-Crohn's disease, or inflamed with non-inflamed tissue. Integrative methylation and gene expression analyses revealed dysregulation of genes associated to the PRKACA and E2F1 network, which is involved in cell cycle progression, angiogenesis, epithelial to mesenchymal transition, and bile metabolism.
Our research provides evidence that the methylome and the transcriptome are systematically dysregulated in stenosis-associated fibroblasts.
The aim of this work is to develop a pragmatic approach in the assessment and management strategies of patients with cirrhosis in order to optimize the outcomes in this patient population.
A ...systematic review of literature was conducted through 8 July 2017 on the PubMed Database looking for key terms, such as malnutrition, nutrition, assessment, treatment, and cirrhosis. Articles and studies looking at associations between nutrition and cirrhosis were reviewed.
An assessment of malnutrition should be conducted in two stages: the first, to identify patients at risk for malnutrition based on the severity of liver disease, and the second, to perform a complete multidisciplinary nutritional evaluation of these patients. Optimal management of malnutrition should focus on meeting recommended daily goals for caloric intake and inclusion of various nutrients in the diet. The nutritional goals should be pursued by encouraging and increasing oral intake or using other measures, such as oral supplementation, enteral nutrition, or parenteral nutrition.
Although these strategies to improve nutritional support have been well established, current literature on the topic is limited in scope. Further research should be implemented to test if this enhanced approach is effective.
Targeted muscle reinnervation (TMR) has been shown to reduce phantom limb pain (PLP) and residual limb pain (RLP) after major limb amputation. However, the effect of the timing of surgery on pain ...control and quality of life outcomes is controversial. We conducted a retrospective study to compare the outcomes of acute TMR for pain prevention with non-acute TMR for the treatment of established pain.
All patients treated with TMR in our institution between January 2018 and December 2021 were evaluated at 6, 12, 18 and 24 months post-operatively. Pain intensity and quality of life outcomes were assessed using the Brief Pain Inventory (Pain Severity and Pain Interference scales) and Pain Catastrophizing Scale. Outcomes were compared between acute and non-acute TMR using the Wilcoxon ranked-sum test or Fisher’s exact test as appropriate. Multilevel mixed-effects linear regression was used to account for repeat measures and potential pain confounders.
Thirty-two patients with 38 major limb amputations were included. Acute TMR patients reported significantly lower RLP and PLP scores, pain interference and pain catastrophisation at all time points (p < 0.05). Acute TMR was significantly associated with lower pain severity and pain interference in a linear mixed-effects model accounting for patient age, gender, amputation indication, amputation site, time post-TMR and repeated surveys (p < 0.05). There was no significant difference in the complication rate (p = 0.51).
Acute TMR was associated with clinically and statistically significant pain outcomes that were better than that in non-acute TMR. This suggests that TMR should be performed with preventative intent, when possible, as part of a multidisciplinary approach to pain management, rather than deferred until the development of chronic pain.
Acetylcholinesterase (AChE) hydrolyzes acetylcholine (ACh), a vital neurotransmitter that regulates muscle movement and brain function, including memory, attention, and learning. Inhibition of AChE ...activity can cause a variety of adverse health effects and toxicity. Identifying AChE inhibitors quickly and efficiently warrants developing AChE inhibition assays in a quantitative, high-throughput screening (qHTS) platform. In this chapter, protocols for multiple homogenous AChE inhibition assays used in a qHTS system are provided. These AChE inhibition assays include a (1) human neuroblastoma (SH-SY5Y) cell-based assay with fluorescence or colorimetric detection; (2) human recombinant AChE with fluorescence or colorimetric detection; and (3) combination of human recombinant AChE and liver microsomes with colorimetric detection, which enables detection of test compounds requiring metabolic activation to become AChE inhibitors. Together, these AChE assays can help identify, prioritize, and predict chemical hazards in large compound libraries using qHTS systems.
•Past authoritarian experience affects current online political psychology.•The cultural legacy of history should be considered to explain OPE.•The influence of new media is contingent on both ...current and historical variables.
This paper represents an effort to investigate the impact of perceived new media credibility on citizens’ online political efficacy (OPE) in new democracies. Unlike their counterparts in mature democracies and outright authoritarian states, citizens of new democracies face the challenge to reconcile their democratic present with the authoritarian past. Their online political behaviors therefore are likely to be shaped by the interaction between democratic realities and authoritarian legacies or memories. The current study argues that in new democracies, the relationship between credibility of new media and OPE is contingent upon citizens’ authoritarian experience. Since authoritarian experience delivers a sense of relative acquisition through a comparison mechanism, it is expected to play a positive role in moderating the association between credibility of new media and OPE. We test the proposition by studying a sample of Taiwanese residents interviewed during the 2015 Taiwan Communication Survey (TCS). Our empirical analyses produce strong supportive evidence for the positive conditioning effect of authoritarian experience and the result is robust to different model specifications and alternative measures of authoritarian experience.
For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have ...reported a phenomenon known as “accelerated blood clearance (ABC)” where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane‐coated Fe3O4 nanoparticles (Fe3O4@RBC NPs) rely on CD47, which is a “don't eat me” marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein‐alpha (SIRP‐α) receptor. Fe3O4@RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe3O4@RBC NPs does not elicit immune responses on neither the cellular level (myeloid‐derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane‐camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long‐existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.
Red blood cell membrane‐camouflaged Fe3O4 nanoparticles (Fe3O4@RBC NPs) exhibit prolonged circulation time in the blood with no adverse effects. There is little change between a first and second dose, and no accelerated blood clearance is seen, as is generally the case for PEGylated nanomaterials. This is a significant advancement toward developing biomaterials that are able to resist both immune response and rapid clearance.
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