Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. ...Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shock wave treatment. Shock wave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shock wave treatment induced proliferation and increased wound healing in an Erk1/2-dependent fashion. In summary, this report demonstrates that shock wave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shock wave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shock wave treatment for wound healing.
Extracorporeal shockwave treatment was shown to improve orthopaedic diseases and wound healing and to stimulate lymphangiogenesis in vivo. The aim of this study was to investigate in vitro shockwave ...treatment (IVSWT) effects on lymphatic endothelial cell (LEC) behavior and lymphangiogenesis. We analyzed migration, proliferation, vascular tube forming capability and marker expression changes of LECs after IVSWT compared with HUVECs. Finally, transcriptome- and miRNA analyses were conducted to gain deeper insight into the IVSWT-induced molecular mechanisms in LECs. The results indicate that IVSWT-mediated proliferation changes of LECs are highly energy flux density-dependent and LEC 2D as well as 3D migration was enhanced through IVSWT. IVSWT suppressed HUVEC 3D migration but enhanced vasculogenesis. Furthermore, we identified podoplaninhigh and podoplaninlow cell subpopulations, whose ratios changed upon IVSWT treatment. Transcriptome- and miRNA analyses on these populations showed differences in genes specific for signaling and vascular tissue. Our findings help to understand the cellular and molecular mechanisms underlying shockwave-induced lymphangiogenesis in vivo.
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Inflammation processes are associated with significant decreases in tissue or lysosomal pH from 7.4 to 4, a fact that argues for the application of pH-responsive drug delivery ...systems. However, for their design and optimization a full understanding of the release mechanism is crucial.
In this study we investigated the pH-depending drug release mechanism and the influence of silk fibroin (SF) concentration and SF degradation degree of human serum albumin (HSA)-SF nanocapsules. Sonochemically produced nanocapsules were investigated regarding particle size, colloidal stability, protein encapsulation, thermal stability and drug loading properties. Particles of the monodisperse phase showed average hydrodynamic radii between 438 and 888 nm as measured by DLS and AFM and a zeta potential of −11.12 ± 3.27 mV. Together with DSC results this indicated the successful production of stable nanocapsules. ATR-FTIR analysis demonstrated that SF had a positive effect on particle formation and stability due to induced beta-sheet formation and enhanced crosslinking.
The pH-responsive release was found to depend on the SF concentration. In in-vitro release studies, HSA-SF nanocapsules composed of 50% SF showed an increased pH-responsive release for all tested model substances (Rhodamine B, Crystal Violet and Evans Blue) and methotrexate at the lowered pH of 4.5 to pH 5.4, while HSA capsules without SF did not show any pH-responsive drug release.
Mechanistic studies using confocal laser scanning microscopy (CLSM) and small angle X-ray scattering (SAXS) analyses showed that increases in particle porosity and decreases in particle densities are directly linked to pH-responsive release properties. Therefore, the pH-responsive release mechanism was identified as diffusion controlled in a novel and unique approach by linking scattering results with in-vitro studies. Finally, cytotoxicity studies using the human monocytic THP-1 cell line indicated non-toxic behavior of the drug loaded nanocapsules when applied in a concentration of 62.5 µg mL−1.
Based on the obtained release properties of HSA-SF nanocapsules formulations and the results of in-vitro MTT assays, formulations containing 50% SF showed the highest requirements arguing for future in vivo experiments and application in the treatment of inflammatory diseases.
Osteoarthritis (OA) is one of the most common causes of disability and represents a major socio-economic burden. Despite intensive research, the molecular mechanisms responsible for the initiation ...and progression of OA remain inconclusive. In recent years experimental findings revealed elevated levels of reactive oxygen species (ROS) as a major factor contributing to the onset and progression of OA. Hence, we designed a hydrostatic pressure bioreactor system that is capable of stimulating cartilage cell cultures with elevated ROS levels. Increased ROS levels in the media did not only lead to an inhibition of glycosaminoglycans and collagen II formation but also to a reduction of already formed glycosaminoglycans and collagen II in chondrogenic mesenchymal stem cell pellet cultures. These effects were associated with the elevated activity of matrix metalloproteinases as well as the increased expression of several inflammatory cytokines. ROS activated different signaling pathways including PI3K/Akt and MAPK/ERK which are known to be involved in OA initiation and progression. Utilizing the presented bioreactor system, an OA in vitro model based on the generation of ROS was developed that enables the further investigation of ROS effects on cartilage degradation but can also be used as a versatile tool for anti-oxidative drug testing.
Soil moisture is a key modifier of runoff generation from rainfall excess, including during extreme precipitation events associated with Atmospheric Rivers (ARs). This paper presents a new, publicly ...available dataset from a soil moisture monitoring network in Northern California's Russian River Basin, designed to assess soil moisture controls on runoff generation under AR conditions. The observations consist of 2‐min volumetric soil moisture at 19 sites and 6 depths (5, 10, 15, 20, 50, and 100 cm), starting in summer 2017. The goals of this monitoring network are to aid the development of research applications and situational awareness tools for Forecast‐Informed Reservoir Operations at Lake Mendocino. We present short analyses of these data to demonstrate their capability to characterize soil moisture responses to precipitation across sites and depths, including time series analysis, correlation analysis, and identification of soil saturation thresholds that induce runoff. Our results show strong inter‐site Pearson's correlations (>0.8) at the seasonal timescale. Correlations are strong (>0.8) during events with high antecedent soil moisture and during drydown periods, and weak (<0.5) otherwise. High event runoff ratios are observed when antecedent soil moisture thresholds are exceeded, and when antecedent runoff is high. Although local heterogeneity in soil moisture can limit the utility of point source data in some hydrologic model applications, our analyses indicate three ways in which soil moisture data are valuable for model design: (1) sensors installed at 6 depths per location enable us to identify the soil depth below which evapotranspiration and saturation dynamics change, and therefore choose model soil layer depths, (2) time series analysis indicates the role of soil moisture processes in controlling runoff ratio during precipitation, which hydrologic models should replicate, and (3) spatial correlation analysis of the soil moisture fluctuations helps identify when and where distributed hydrologic modelling may be beneficial.
We present a publicly available, high‐resolution soil moisture dataset from Russian River Basin in California designed to assess soil moisture controls on runoff generation under atmospheric river conditions. Analyses of the results demonstrate that: (1) Multi‐depth sensors are valuable for identifying which depths show differences in evapotranspiration and soil saturation dynamics, (2) Understanding the factors influencing event runoff ratio during a precipitation event enables us to design evaluation techniques and indicates soil moisture processes that distributed hydrologic models should replicate.
Abstract Short-duration, high-intensity rainfall in Southern California, often associated with narrow cold-frontal rainbands (NCFR), threaten life and property. While the mechanisms that drive NCFRs ...are relatively well understood, their regional characteristics, specific contribution to precipitation hazards, and their predictability in the western United States have received little research attention relative to their impact. This manuscript presents observations of NCFR physical processes made during the Atmospheric River Reconnaissance field campaign on 2 February 2019 and investigates the predictability of the observed NCFR across spatiotemporal scales and forecast lead time. Dropsonde data collected along transects of an atmospheric river (AR) and its attendant cyclone during rapid cyclogenesis, and radiosonde observations during landfall 24 h later, are used to demonstrate that a configuration of the Weather Research and Forecasting (WRF) Model skillfully reproduces the physical processes responsible for the development and maintenance of the impactful NCFR. Ensemble simulations provide quantitative uncertainty information on the representation of these features in numerical weather prediction and instill confidence in the utility of WRF as a forecast guidance tool for short- to medium-range prediction of mesoscale precipitation processes in landfalling ARs. This research incorporates novel data and methodologies to improve forecast guidance for NCFRs impacting Southern California. While this study focuses on a single event, the outlined approach to observing and predicting high-impact weather across a range of spatial and temporal scales will support regional water management and hazard mitigation, in general.
Management of infected wounds is one of the most costly procedures in the health care sector. Burn wounds are of significant importance due to the high infection risk that can possibly lead to severe ...consequences such as sepsis. Because antibiotic wound treatments have caused increasing antibiotic resistance in bacteria, there is currently a strong need for alternative strategies. Therefore, we developed new antimicrobial wound dressings consisting of pH-responsive human serum albumin/silk fibroin nanocapsules immobilized onto cotton/polyethylene terephthalate (PET) blends loaded with eugenol, which is an antimicrobial phenylpropanoid. Ultrasound-assisted production of eugenol-loaded nanocapsules resulted in particle sizes (hydrodynamic radii) between 319.73 ± 17.50 and 574.00 ± 92.76 nm and zeta potentials ranging from −10.39 ± 1.99 mV to −12.11 ± 0.59 mV. Because recent discoveries have indicated that the sweat glands contribute to wound reepithelialisation, release studies of eugenol were conducted in different artificial sweat formulas that varied in pH. Formulations containing 10% silk fibroin with lower degradation degree exhibited the highest release of 41% at pH 6.0. After immobilization, the functionalized cotton/PET blends were able to inhibit 81% of
Staphylococcus aureus
and 33% of
Escherichia coli
growth. Particle uniformity, silk fibroin concentration, and high surface-area-to-volume ratio of the produced nanocapsules were identified as the contributing factors leading to high antimicrobial activities against both strains. Therefore, the production of antimicrobial textiles using nanocapsules loaded with an active natural compound that will not contribute to antibiotic resistance is seen as a potential future alternative to commercially available antiseptic wound dressings.
New antimicrobial pH-responsive wound dressings consisting of immobilized human serum albumin/silk fibroin nanocapsules were developed.
Introduction
Emotional intelligence (EI) is associated with a range of positive health, wellbeing, and behavioral outcomes. The present article describes the development and validation of an online ...training program for increasing EI abilities in adults. The training program was based on theoretical models of emotional functioning and empirical literature on successful approaches for training socioemotional skills and resilience.
Methods
After an initial design, programming, and refinement process, the completed online program was tested for efficacy in a sample of 326 participants (72% female) from the general population. Participants were randomly assigned to complete either the EI training program (
n
= 168) or a matched placebo control training program (
n
= 158). Each program involved 10-12 hours of engaging online content and was completed during either a 1-week (
n
= 175) or 3-week (
n
= 151) period.
Results
Participants who completed the EI training program showed increased scores from pre- to post-training on standard self-report (i.e., trait) measures of EI (relative to placebo), indicating self-perceived improvements in recognizing emotions, understanding emotions, and managing the emotions of others. Moreover, those in the EI training also showed increased scores in standard performance-based (i.e., ability) EI measures, demonstrating an increased ability to strategically use and manage emotions relative to placebo. Improvements to performance measures also remained significantly higher than baseline when measured six months after completing the training. The training was also well-received and described as helpful and engaging.
Discussion
Following a rigorous iterative development process, we created a comprehensive and empirically based online training program that is well-received and engaging. The program reliably improves both trait and ability EI outcomes and gains are sustained up to six months post-training. This program could provide an easy and scalable method for building emotional intelligence in a variety of settings.
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