Aerogels from Cellulose Phosphates of Low Degree of Substitution: A TBAF·H2O/DMSO Based Approach.

Biopolymer aerogels of appropriate open-porous morphology, nanotopology, surface chemistry, and mechanical properties can be promising cell scaffolding materials. Here, we report a facile approach towards the preparation of cellulose phosphate aerogels from two types of cellulosic source materials. Since high degrees of phosphorylation would afford water-soluble products inappropriate for cell scaffolding, products of low DSP (ca. 0.2) were prepared by a heterogeneous approach. Aiming at both i) full preservation of chemical integrity of cellulose during dissolution and ii) utilization of specific phase separation mechanisms upon coagulation of cellulose, TBAF·H2O/DMSO was employed as a non-derivatizing solvent. Sequential dissolution of cellulose phosphates, casting, coagulation, solvent exchange, and scCO2 drying afforded lightweight, nano-porous aerogels. Compared to their non-derivatized counterparts, cellulose phosphate aerogels are less sensitive towards shrinking during solvent exchange. This is presumably due to electrostatic repulsion and translates into faster scCO2 drying. The low DSP values have no negative impact on pore size distribution, specific surface (SBET ≤ 310 m2 g-1), porosity (Π 95.5-97 vol.%), or stiffness (Eρ ≤ 211 MPa cm3 g-1). Considering the sterilization capabilities of scCO2, existing templating opportunities to afford dual-porous scaffolds and the good hemocompatibility of phosphorylated cellulose, TBAF·H2O/DMSO can be regarded a promising solvent system for the manufacture of cell scaffolding materials.

Independent Predictors for Higher Postoperative Pain Intensity During Recovery After Open Thoracic Surgery: A Retrospective Analysis in 621 Patients.

Objective: To evaluate two standard procedure-specific pain regimens and to assess independent predictors for higher pain intensity after thoracic surgery. Methods: Patients received either oral opioid analgesia (Opioid Group) or epidural analgesia and were then bridged to systemic opioid analgesia (EDA + O Group) in this retrospective observational study. Medical history, discharge letters, anesthetic protocols, and pain protocols were evaluated in 621 patients after open thoracotomy and assessed with a stepward back elimination in a multivariate logistic regression model. Results: Data of 621 thoracotomies in 2014 were analyzed, 309 patients in the Opioid Group and 312 patients in the EDA + O Group. Pain scores at rest and on coughing were significantly lower in the EDA + O Group on postoperative days (PODs) 1-4 (P < 0.001). Stepwise backward elimination in multivariate logistic regression identified preexisting pain disease (P = 0.034), no epidural analgesia (P < 0.001), opioids in preoperative pain therapy (P < 0.001), and antidepressant medication (P = 0.003) as independent risk factors for higher pain intensity at rest on PODs 1-4. Same on PODs 5-8 with regard to opioids in preoperative pain therapy (P < 0.001) and antidepressant medication (P = 0.018). Moreover, on PODs 5-8, male gender had a lower risk (P < 0.003) for pain, and preexisting musculosceletal disease had a lower risk for more postoperative pain (P = 0.009). On coughing, male gender and younger age proved to have a lower risk for postoperative pain on PODs 1-8 and on PODs 1-4, respectively. Opioids in preexisting pain therapy and antidepressant medication were identified as risk factors for pain on PODs 1-8 on coughing, and pain disease was identified as a risk factor for more pain on PODs 1-4 (P = 0.041). Moreover, preexisting cardiac disease indicated more pain on PODs 1-4 (P = 0.05), and musculoskeletal disease and neurological disease indicated more pain on PODs 5-8 (P = 0.041, and P = 0.023). Conclusions: We present data on independent risk factors for higher pain intensity during recovery after thoracotomy. The lack of postoperative epidural analgesia, female gender, preexisting opioid pain therapy, and chronic pain are the strongest risk factors for higher pain intensity. Antidepressant medication was identified as an independent risk factor at rest and on coughing on all PODs. Study limitations: The study design is retrospective.

Influence of capillary bridge formation onto the silica nanoparticle interaction studied by grand canonical Monte Carlo simulations.

Adhesion forces between nanoparticles strongly depend on the amount of adsorbed condensed water from ambient atmosphere. Liquid water forms bridges in the cavities separating the particles, giving rise to the so-called capillary forces which in most cases dominate the van der Waals and long-range electrostatic interactions. Capillary forces promote the undesirable agglomeration of particles to large clusters, thereby hindering the flowability of dry powders in process containers. In process engineering macroscopic theories based on the Laplace pressures are used to estimate the strength of the capillary forces. However, especially for low relative humidity and when the wetting of rough or small nanoparticles is studied, those theories can fail. Molecular dynamic simulations can help to give better insight into the water-particle interface. The simulated force versus distance curve as well as adhesion forces and the adsorption isotherm for silica nanoparticles at varying relative humidity will be discussed in comparison to experiments, theories, and simulations.

Discovery of novel regulatory peptides by reverse pharmacology: spotlight on chemerin and the RF-amide peptides metastin and QRFP.

Reverse pharmacology is a screening technology that matches G protein-coupled receptors (GPCRs) with unknown cognate ligands in cell-based screening assays by detection of agonist-induced signaling pathways. One decade spent pursuing orphan GPCR screening by this technique assigned over 30 ligand/receptor pairs and revealed previously known or novel undescribed ligands, mostly of a peptidic nature. In this review, we describe the discovery, characterization of the structural composition, biological function, physiological role and therapeutic potential of three recently identified peptidic ligands. These are metastin, QRFP in a context of five RF-amide genes described in humans and the chemoattractant, chemerin. Metastin was initially characterized as a metastasis inhibitor. Investigations using ligand/receptor pairing revealed that metastin was involved in a variety of physiological processes, including endocrine function during pregnancy and gonad development. The novel RF-amide QRFP is implicated in food intake and aldosterone release from the adrenal cortex in the rat. Chemerin, first described as TIG2, is upregulated in tazarotene-treated psoriatic skin. By GPCR screening, bioactive chemerin was isolated from ovarial carcinoma fluid as well as hemofiltrate. Characterization as a chemoattractant for immature dendritic cells and analysis of the expression profile of metastin and its receptor suggested a physiological role of chemerin as a mediator of the immune response, inflammatory processes and bone development.

Identification and functional characterization of hemorphins VV-H-7 and LVV-H-7 as low-affinity agonists for the orphan bombesin receptor subtype 3.

1. The human orphan G-protein coupled receptor bombesin receptor subtype 3 (hBRS-3) was screened for peptide ligands by a Ca(2+)mobilization assay resulting in the purification and identification of two specific ligands, the naturally occurring VV-hemorphin-7 (VV-H-7) and LVV-hemorphin-7 (LVV-H-7), from human placental tissue. These peptides were functionally characterized as full agonists with unique specificity albeit low affinity for hBRS-3 compared to other bombesin receptors. 2. VV-H-7 and LVV-H-7 induced a dose-dependent response in hBRS-3 overexpressing CHO cells, as well as in NCI-N417 cells expressing the hBRS-3 endogenously. The affinity of VV-H-7 was higher in NCI-N417 cells compared to overexpressing CHO cells. In detail, the EC(50) values were 45+/-15 microM for VV-H-7 and 183+/-60 microM for LVV-H-7 in CHO cells, and 19+/-6 microM for VV-H-7 and 38+/-18 microM for LVV-H-7 in NCI-N417 cells. Other hemorphins had no effect. Gastrin-releasing peptide (GRP) and neuromedin B (NMB) showed similar EC(50) values of 13-20 microM (GRP) and of 1-2 microM (NMB) on both cell lines. 3. Structure-function analysis revealed that both the N-terminal valine and the C-terminal phenylalanine residues of VV-H-7 are critical for the ligand-receptor interaction. 4. Endogenous hBRS-3 in NCI-N417 activated by VV-H-7 couples to phospholipase C resulting in changes of intracellular calcium, which is initially released from an inositol trisphosphate (IP(3))-sensitive store followed by a capacitive calcium entry from extracellular space. 5. VV-H-7-induced hBRS-3 activation led to phosphorylation of p42/p44-MAP kinase in NCI-N417 cells, but did not stimulate cell proliferation. In contrast, phosphorylation of focal adhesion kinase (p125(FAK)) was not observed.

A three-step purification strategy for isolation of hamster TIG2 from CHO cells: characterization of two processed endogenous forms.

We have recently isolated a bioactive, circulating protein of human tazarotene-induced gene-2 (TIG2) as the natural ligand of the orphan receptor ChemR23. Here we describe a simplified method for the isolation of hamster TIG2 protein from Chinese hamster ovary (CHO) cell supernatant. Using a heparin-affinity column followed by two reversed phase chromatography steps resulted in the isolation of pure biologically active material. Two processed bioactive forms of Chinese hamster TIG2 were identified by Edman sequencing and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) mass fingerprint analysis, representing the amino acid residues T20 to F156, and T20 to A155 of the 163 amino acid propeptide. Comparison with the predicted aa-sequence indicates a mutation or modification within the C-terminal end of the peptide.

Simulation of Forces between Humid Amorphous Silica Surfaces: A Comparison of Empirical Atomistic Force Fields.

Atmospheric humidity strongly influences the interactions between dry granular particles in process containers. To reduce the energy loss in industrial production processes caused by particle agglomeration, a basic understanding of the dependence of particle interactions on humidity is necessary. Hence, in this study, molecular dynamic simulations were carried out to calculate the adhesion between silica surfaces in the presence of adsorbed water. For a realistic description, the choice of force field is crucial. Because of their frequent use and transferability to biochemical systems, the Clay and CWCA force fields were investigated with respect to their ability to describe the water-silica interface in comparison to the more advanced Reax force field, ab initio calculations, and experiments.

Aerogels from unaltered bacterial cellulose: application of scCO2 drying for the preparation of shaped, ultra-lightweight cellulosic aerogels.

Bacterial cellulose produced by the gram-negative bacterium Gluconacetobacter xylinum was found to be an excellent native starting material for preparing shaped ultra-lightweight cellulose aerogels. The procedure comprises thorough washing and sterilization of the aquogel, quantitative solvent exchange and subsequent drying with supercritical carbon dioxide at 40 degrees C and 100 bar. The average density of the obtained dry cellulose aerogels is only about 8 mg x cm(-3) which is comparable to the most lightweight silica aerogels and distinctly lower than all values for cellulosic aerogels obtained from plant cellulose so far. SEM, ESEM and nitrogen adsorption experiments at 77 K reveal an open-porous network structure that consists of a comparatively high percentage of large mesopores and smaller macropores.