Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. Our previous study revealed that quercetin could suppress the expression of matrix ...metalloprotease-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) to achieve anti-inflammatory effects in tumor necrosis factor-α (TNF-α)-stimulated human retinal pigment epithelial (ARPE-19) cells. The present study explored whether quercetin can inhibit the interleukin-1β (IL-1β)-induced production of inflammatory cytokines and chemokines in ARPE-19 cells. Prior to stimulation by IL-1β, ARPE-19 cells were pretreated with quercetin at various concentrations (2.5-20 µM). The results showed that quercetin could dose-dependently decrease the mRNA and protein levels of ICAM-1, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1). It also attenuated the adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. We also demonstrated that quercetin inhibited signaling pathways related to the inflammatory process, including phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of nuclear factor κ-B kinase (IKK)α/β, c-Jun, cAMP response element-binding protein (CREB), activating transcription factor 2 (ATF2) and nuclear factor (NF)-κB p65, and blocked the translocation of NF-κB p65 into the nucleus. Furthermore, MAPK inhibitors including an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (U0126), a p38 inhibitor (SB202190) and a c-Jun N-terminal kinase (JNK) inhibitor (SP600125) decreased the expression of soluble ICAM-1 (sICAM-1), but not ICAM-1. U0126 and SB202190 could inhibit the expression of IL-6, IL-8 and MCP-1, but SP600125 could not. An NF-κB inhibitor (Bay 11-7082) also reduced the expression of ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1. Taken together, these results provide evidence that quercetin protects ARPE-19 cells from the IL-1β-stimulated increase in ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways to ameliorate the inflammatory response.
Implantable neural probes are widely used to record and stimulate neural activities. These probes should be stiff enough for insertion. However, it should also be flexible to minimize tissue damage ...after insertion. Therefore, having dynamic control of the neural probe shank flexibility will be useful. For the first time, we have successfully fabricated flexible neural probes with embedded microfluidic channels for dynamic control of neural probe stiffness by controlling fluidic pressure in the channels. The present hybrid neural probes consisted of polydimethylsiloxane (PDMS) and polyimide (PI) layers could provide the required stiffness for insertion and flexibility during operation. The PDMS channels were fabricated by reversal imprint using a silicon mold and bonded to a PI layer to form the embedded channels in the neural probe. The probe shape was patterned using an oxygen plasma generated by an inductively coupled plasma etching system. The critical buckling force of PDMS/PI neural probes could be tuned from 0.25-1.25 mN depending on the applied fluidic pressure in the microchannels and these probes were successfully inserted into a 0.6% agarose gel that mimicked the stiffness of the brain tissue. Polymer-based neural probes are typically more flexible than conventional metal wire-based probes, and they could potentially provide less tissue damage after implantation.
Poor research reporting is a major contributing factor to low study reproducibility, financial and animal waste. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were ...developed to improve reporting quality and many journals support these guidelines. The influence of this support is unknown. We hypothesized that papers published in journals supporting the ARRIVE guidelines would show improved reporting compared with those in non-supporting journals. In a retrospective, observational cohort study, papers from 5 ARRIVE supporting (SUPP) and 2 non-supporting (nonSUPP) journals, published before (2009) and 5 years after (2015) the ARRIVE guidelines, were selected. Adherence to the ARRIVE checklist of 20 items was independently evaluated by two reviewers and items assessed as fully, partially or not reported. Mean percentages of items reported were compared between journal types and years with an unequal variance t-test. Individual items and sub-items were compared with a chi-square test. From an initial cohort of 956, 236 papers were included: 120 from 2009 (SUPP; n = 52, nonSUPP; n = 68), 116 from 2015 (SUPP; n = 61, nonSUPP; n = 55). The percentage of fully reported items was similar between journal types in 2009 (SUPP: 55.3 ± 11.5% SD; nonSUPP: 51.8 ± 9.0%; p = 0.07, 95% CI of mean difference -0.3-7.3%) and 2015 (SUPP: 60.5 ± 11.2%; nonSUPP; 60.2 ± 10.0%; p = 0.89, 95%CI -3.6-4.2%). The small increase in fully reported items between years was similar for both journal types (p = 0.09, 95% CI -0.5-4.3%). No paper fully reported 100% of items on the ARRIVE checklist and measures associated with bias were poorly reported. These results suggest that journal support for the ARRIVE guidelines has not resulted in a meaningful improvement in reporting quality, contributing to ongoing waste in animal research.
There is a realistic expectation that the global effort in vaccination will bring the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under control. Nonetheless, ...uncertainties remain about the type of long-term association that the virus will establish with the human population and, in particular, whether coronavirus disease 2019 (COVID-19) will become an endemic disease. Although the trajectory is difficult to predict, the conditions, concepts and variables that influence this transition can be anticipated. Persistence of SARS-CoV-2 as an endemic virus, perhaps with seasonal epidemic peaks, may be fuelled by pockets of susceptible individuals and waning immunity after infection or vaccination, changes in the virus through antigenic drift that diminish protection and re-entries from zoonotic reservoirs. Here we review relevant observations from previous epidemics and discuss the potential evolution of SARS-CoV-2 as it adapts during persistent transmission in the presence of a level of population immunity. Lack of effective surveillance or adequate response could enable the emergence of new epidemic or pandemic patterns from an endemic infection of SARS-CoV-2. There are key pieces of data that are urgently needed in order to make good decisions; we outline these and propose a way forward.
Acute Heart Failure Syndromes Gheorghiade, Mihai, MD, FACC; Pang, Peter S., MD
Journal of the American College of Cardiology,
02/2009, Letnik:
53, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Heart failure resulting in hospitalization represents a significant and growing health care burden. Heterogeneity characterizes this group in terms of mode of presentation, pathophysiology, and ...prognosis. The vast majority of patients symptomatically improve during hospitalization; however, their early post-discharge rehospitalization and mortality rates continue to be high. Worsening signs and symptoms, neurohormonal, and renal abnormalities occurring soon after discharge may contribute to these high post-discharge event rates. Currently available assessment modalities combined with recent advances in cardiovascular therapies provide present-day opportunities to improve post-discharge outcomes. Further investigation into pathophysiologic targets and novel approaches to clinical trial design are needed. Improving post-discharge outcomes is the single most important goal in the management of acute heart failure syndromes.
The extracellular matrix (ECM) serves as a complex scaffold with diverse physical dimensions and surface properties influencing NPC cell migration. Polydimethylsiloxane (PDMS), a widely used ...biocompatible material, is hydrophobic and undesirable for cell seeding. Thus, the establishment of a biomimetic model with varied topographies and surface properties is essential for effective NPC43 cell separation from NP460 cells. This study explored how ECM surface properties influence NP460 and NPC43 cell behaviors via plasma treatments and chemical modifications to alter the platform surface. In addition to the conventional oxygen/nitrogen (O
/N
) plasma treatment, O
and argon plasma treatments were utilized to modify the platform surface, which increased the hydrophilicity of the PDMS platforms, resulting in enhanced cell adhesion. (3-aminopropyl)triethoxysilane and fibronectin (FN) were used to coat the PDMS platforms uniformly and selectively. The chemical coatings significantly affected cell motility and spreading, as cells exhibited faster migration, elongated cell shapes, and larger spreading areas on FN-coated surfaces. Furthermore, narrower top layer trenches with 5 µm width and a lower concentration of 10 µg/mL FN were coated selectively on the platforms to limit NP460 cell movements and enhance NPC43 cell separation efficiency. A significantly high separation efficiency of 99.4% was achieved on the two-layer scaffold platform with 20/5 µm wide ridge/trench (R/T) as the top layer and 40/10 µm wide R/T as the bottom layer, coupling with 10 µg/mL FN selectively coated on the sidewalls of the top and bottom layers. This work demonstrated an innovative application of selective FN coating to direct cell behavior, offering a new perspective to probe into the subtleties of NPC cell separation efficiency. Moreover, this cost-effective and compact microsystem sets a new benchmark for separating cancer cells.
Abstract
CATH (https://www.cathdb.info) identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural and functional ...annotations. There are two levels: CATH-B, a daily snapshot of the latest domain structures and superfamily assignments, and CATH+, with additional derived data, such as predicted sequence domains, and functionally coherent sequence subsets (Functional Families or FunFams). The latest CATH+ release, version 4.3, significantly increases coverage of structural and sequence data, with an addition of 65,351 fully-classified domains structures (+15%), providing 500 238 structural domains, and 151 million predicted sequence domains (+59%) assigned to 5481 superfamilies. The FunFam generation pipeline has been re-engineered to cope with the increased influx of data. Three times more sequences are captured in FunFams, with a concomitant increase in functional purity, information content and structural coverage. FunFam expansion increases the structural annotations provided for experimental GO terms (+59%). We also present CATH-FunVar web-pages displaying variations in protein sequences and their proximity to known or predicted functional sites. We present two case studies (1) putative cancer drivers and (2) SARS-CoV-2 proteins. Finally, we have improved links to and from CATH including SCOP, InterPro, Aquaria and 2DProt.
Automatic shadow detection is a very important pre-processing step for many remote sensing applications, particularly for images acquired with high spatial resolution. In complex urban environments, ...shadows may occupy a significant portion of the image. Ignoring these regions would lead to errors in various applications, such as atmospheric correction and classification. To better understand the radiative impact of shadows, a physical study was conducted through the simulation of a synthetic urban canyon scene. Its results helped to explain the most common assumptions made on shadows from a physical point of view in the literature. With this understanding, state-of-the-art methods on shadow detection were surveyed and categorized into six classes: histogram thresholding, invariant color models, object segmentation, geometrical methods, physics-based methods, unsupervised and supervised machine learning methods. Among them, some methods were selected and tested on a large dataset of multispectral and hyperspectral airborne images with high spatial resolution. The dataset chosen contains a large variety of typical occidental urban scenes. The results were compared based on accurate reference shadow masks. In these experiments, histogram thresholding on RGB and NIR channels performed the best with an average accuracy of 92.5%, followed by physics-based methods, such as Richter’s method with 90.0%. Finally, this paper analyzes and discusses the limits of these algorithms, concluding with some recommendations for shadow detection.
Grimace scales have been used for pain assessment in different species. This study aimed to develop and validate the Feline Grimace Scale (FGS) to detect naturally-occurring acute pain. Thirty-five ...client-owned and twenty control cats were video-recorded undisturbed in their cages in a prospective, case-control study. Painful cats received analgesic treatment and videos were repeated one hour later. Five action units (AU) were identified: ear position, orbital tightening, muzzle tension, whiskers change and head position. Four observers independently scored (0-2 for each AU) 110 images of control and painful cats. The FGS scores were higher in painful than in control cats; a very strong correlation with another validated instrument for pain assessment in cats was observed (rho = 0.86, p < 0.001) as well as good overall inter-rater reliability ICC = 0.89 (95% CI: 0.85-0.92), excellent intra-rater reliability (ICC > 0.91), and excellent internal consistency (Cronbach's alpha = 0.89). The FGS detected response to analgesic treatment (scores after analgesia were lower than before) and a cut-off score was determined (total pain score > 0.39 out of 1.0). The FGS is a valid and reliable tool for acute pain assessment in cats.
We examine the basinwide trends in sea ice circulation and drift speed and highlight the changes between 1982 and 2009 in connection to regional winds, multiyear sea ice coverage, ice export, and the ...thinning of the ice cover. The polarity of the Arctic Oscillation (AO) is used as a backdrop for summarizing the variance and shifts in decadal drift patterns. The 28‐year circulation fields show a net strengthening of the Beaufort Gyre and the Transpolar Drift, especially during the last decade. The imprint of the arctic dipole anomaly on the mean summer circulation is evident (2001–2009) and enhances summer ice area export at the Fram Strait. Between 2001 and 2009, the large spatially averaged trends in drift speeds (winter: +23.6%/decade, summer: +17.7%/decade) are not explained by the much smaller trends in wind speeds (winter: 1.46%/decade, summer: −3.42%/decade). Notably, positive trends in drift speed are found in regions with reduced multiyear sea ice coverage. Over 90% of the Arctic Ocean has positive trends in drift speed and negative trends in multiyear sea ice coverage. The increased responsiveness of ice drift to geostrophic wind is consistent with a thinner and weaker seasonal ice cover and suggests large‐scale changes in the air‐ice‐ocean momentum balance. The retrieved mean ocean current field from decadal‐scale average ice motion captures a steady drift from Siberia to the Fram Strait, an inflow north of the Bering Strait, and a westward drift along coastal Alaska. This mean current is comparable to geostrophic currents from satellite‐derived dynamic topography.
Key Points
Changes in connection to winds, multiyear ice , export and thinning.
Strengthening of the Beaufort Gyre and the Transpolar Drift.
Positive trends in drift speed are associated with decline in multiyear sea ice.
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