99 research outputs found
Molecular mechanism of basic calcium phosphate crystal-induced activation of human fibroblasts: Role of nuclear factor κB, activator protein 1, and protein kinase C
Synovial fluid basic calcium phosphate (BCP) crystals are markers of severe joint degeneration in osteoarthritis. BCP crystals cause mitogenesis of articular cells and stimulate matrix metalloprotease production, thus promoting degradation of articular tissues. Previous work suggested that BCP crystal-induced cell activation required intracellular crystal dissolution, induction of proto-oncogene expression, and activation of signal transduction pathways involving protein kinase C and mitogen-activated protein kinases. Here we further elucidate the mechanisms of BCP crystal-induced cell activation as BCP crystals activate transcription factors nuclear factor κB and activator protein I in human fibroblasts. We confirm the role of protein kinase C in BCP crystal-induced mitogenesis in human fibroblasts. In contrast, we demonstrate that BCP crystals do not activate signal transduction pathways involving protein tyrosine kinases or phosphatidylinositol 3-kinase. These data further define the mechanism of cell activation by BCP crystals and confirm its selectivity, an observation that may have therapeutic implications
Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins
Water and water-mediated interactions determine thermodynamic and kinetics of
protein folding, protein aggregation and self-assembly in confined spaces. To
obtain insights into the role of water in the context of folding problems, we
describe computer simulations of a few related model systems. The dynamics of
collapse of eicosane shows that upon expulsion of water the linear hydrocarbon
chain adopts an ordered helical hairpin structure with 1.5 turns. The structure
of dimer of eicosane molecules has two well ordered helical hairpins that are
stacked perpendicular to each other. As a prelude to studying folding in
confined spaces we used simulations to understand changes in hydrophobic and
ionic interactions in nano droplets. Solvation of hydrophobic and charged
species change drastically in nano water droplets. Hydrophobic species are
localized at the boundary. The tendency of ions to be at the boundary where
water density is low increases as the charge density decreases. Interaction
between hydrophobic, polar, and charged residue are also profoundly altered in
confined spaces. Using the results of computer simulations and accounting for
loss of chain entropy upon confinement we argue and then demonstrate, using
simulations in explicit water, that ordered states of generic amphiphilic
peptide sequences should be stabilized in cylindrical nanopores
A novel enzymatically-mediated drug delivery carrier for bone tissue engineering applications: combining biodegradable starch-based microparticles and differentiation agents
In many biomedical applications, the performance
of biomaterials depends largely on their degradation
behavior. For instance, in drug delivery applications, the
polymeric carrier should degrade under physiological
conditions slowly releasing the encapsulated drug. The aim
of this work was, therefore, to develop an enzymaticmediated
degradation carrier system for the delivery of
differentiation agents to be used in bone tissue engineering
applications. For that, a polymeric blend of starch with
polycaprolactone (SPCL) was used to produce a microparticle
carrier for the controlled release of dexamethasone
(DEX). In order to investigate the effect of enzymes on the
degradation behavior of the developed system and release
profile of the encapsulated osteogenic agent (DEX), the
microparticles were incubated in phosphate buffer solution
in the presence of a-amylase and/or lipase enzymes (at
physiological concentrations), at 37 C for different periods
of time. The degradation was followed by gravimetric
measurements, scanning electron microscopy (SEM) and
Fourier transformed infrared (FTIR) spectroscopy and the
release of DEX was monitored by high performance liquid
chromatography (HPLC). The developed microparticles
were shown to be susceptible to enzymatic degradation, as observed by an increase in weight loss and porosity with
degradation time when compared with control samples
(incubation in buffer only). For longer degradation times,
the diameter of the microparticles decreased significantly
and a highly porous matrix was obtained. The in vitro
release studies showed a sustained release pattern with
48% of the encapsulated drug being released for a period of
30 days. As the degradation proceeds, it is expected that
the remaining encapsulated drug will be completely
released as a consequence of an increasingly permeable
matrix and faster diffusion of the drug. Cytocompatibility
results indicated the possibility of the developed microparticles
to be used as biomaterial due to their reduced
cytotoxic effects
Factor XIIIA-expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking
Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% of cases. Molecular aberrations in lung adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances in LUSC have not materialized. However, immune checkpoint inhibitors in sub-populations of LUSC patients have led to exciting responses. Using computational analyses of The Cancer Genome Atlas, we identified a subset of LUSC tumors characterized by dense infiltration of inflammatory monocytes (IMs) and poor survival. With novel, immunocompetent metastasis models, we demonstrated that tumor cell derived CCL2-mediated recruitment of IMs is necessary and sufficient for LUSC metastasis. Pharmacologic inhibition of IM recruitment had substantial anti-metastatic effects. Notably, we show that IMs highly express Factor XIIIA, which promotes fibrin cross-linking to create a scaffold for LUSC cell invasion and metastases. Consistently, human LUSC samples containing extensive cross-linked fibrin in the microenvironment correlated with poor survival
Two Types of Planning in Neighborhoods
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68338/2/10.1177_0739456X8400300209.pd
Bases teóricas e experimentais de fatores relacionados com a disponibilidade de potássio do solo às plantas usando trigo como referência
Efeito da temperatura ambiente sobre o desempenho e as características de carcaça de frangos de corte dos 22 aos 42 dias
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
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