34 research outputs found
Development and characterization of a microfluidic model of the tumour microenvironment
The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live ‘window’ into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device’s potential to enable more physiological in vitro drug screening
Petrographical and geochemical evidences for paragenetic sequence interpretation of diagenesis in mixed siliciclastic–carbonate sediments: Mozduran Formation (Upper Jurassic), south of Agh-Darband, NE Iran
The Upper Jurassic Mozduran Formation with a thickness of 420 m at the type locality is the most important gas-bearing reservoir in NE Iran. It is mainly composed of limestone, dolostone with shale and gypsum interbeds that grade into coarser siliciclastics in the easternmost part of the basin. Eight stratigraphic sections were studied in detail in south of the Agh-Darband area. These analyses suggest that four carbonate facies associations and three siliciclastic lithofacies were deposited in shallow marine to shoreline environments, respectively. Cementation, compaction, dissolution, micritization, neomorphism, hematitization, dolomitization and fracturing are diagenetic processes that affected these sediments.Stable isotope variations of δ18O and δ13C in carbonate rocks show two different trends. High depletion of δ18O and low variation of δ13C probably reflect increasing temperatures during burial diagenesis, while the higher depletion in carbon isotope values with low variations in oxygen isotopes are related to fresh water flushing during meteoric diagenesis. Negative values of carbon isotopes may have also resulted from organic matter alteration during penetration of meteoric water. Fe and Mn enrichment with depletion of δ18O also supports the contention that alteration associated with higher depletion in carbon isotope values with low variations in oxygen isotopes took place during meteoric diagenesis. The presence of bright luminescence indicates redox conditions during precipitation of calcite cement
A Bioinformatics Filtering Strategy for Identifying Radiation Response Biomarker Candidates
The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10) of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response
Hypoxic culture of bone marrow-derived mesenchymal stromal stem cells differentially enhances in vitro chondrogenesis within cell-seeded collagen and hyaluronic acid porous scaffolds
Melatonin suppresses senescence‐derived mitochondrial dysfunction in mesenchymal stem cells via the HSPA1L–mitophagy pathway
DIAGENESIS OF NON-MARINE PETROLEUM RESERVOIRS: THE NEOCOMIAN (LOWER CRETACEOUS) SHURIJEH FORMATION, KOPET-DAGH BASIN, NE IRAN
Characterization of Molecules Binding to the 70K N‑Terminal Region of Fibronectin by IFAST Purification Coupled with Mass Spectrometry
Fibronectin (Fn) is a large glycoprotein
present in plasma and
extracellular matrix and is important for many processes. Within Fn
the 70 kDa N-terminal region (70k-Fn) is involved in cell-mediated
Fn assembly, a process that contributes to embryogenesis, development,
and platelet thrombus formation. In addition, major human pathogens
including <i>Staphlycoccus aureus</i> and <i>Streptococcus
pyogenes</i> bind the 70k-Fn region by a novel form of protein–protein
interaction called β-zipper formation, facilitating bacterial
spread and colonization. Knowledge of blood plasma and platelet proteins
that interact with 70k-Fn by β-zipper formation is incomplete.
In the current study, we aimed to characterize these proteins through
affinity purification. For this affinity purification, we used a novel
purification technique termed immiscible filtration assisted by surface
tension (IFAST). The foundation of this technology is immiscible phase
filtration, using a magnet to draw paramagnetic particle (PMP)-bound
analyte through an immiscible barrier (oil or organic solvent) that
separates an aqueous sample from an aqueous eluting buffer. The immiscible
barrier functions to remove unbound proteins via exclusion rather
than dilutive washing used in traditional isolation methods. We identified
31 interactors from plasma, of which only seven were previously known
to interact with Fn. Furthermore, five proteins were identified to
interact with 70k-Fn from platelet lysate, of which one was previously
known. These results demonstrate that IFAST offers advantages for
proteomic studies of interacting molecules in that the technique requires
small sample volumes, can be done with high enough throughput to sample
multiple interaction conditions, and is amenable to exploratory mass
spectrometric and confirmatory immuno-blotting read-outs
Characterization of Molecules Binding to the 70K N‑Terminal Region of Fibronectin by IFAST Purification Coupled with Mass Spectrometry
Fibronectin (Fn) is a large glycoprotein
present in plasma and
extracellular matrix and is important for many processes. Within Fn
the 70 kDa N-terminal region (70k-Fn) is involved in cell-mediated
Fn assembly, a process that contributes to embryogenesis, development,
and platelet thrombus formation. In addition, major human pathogens
including <i>Staphlycoccus aureus</i> and <i>Streptococcus
pyogenes</i> bind the 70k-Fn region by a novel form of protein–protein
interaction called β-zipper formation, facilitating bacterial
spread and colonization. Knowledge of blood plasma and platelet proteins
that interact with 70k-Fn by β-zipper formation is incomplete.
In the current study, we aimed to characterize these proteins through
affinity purification. For this affinity purification, we used a novel
purification technique termed immiscible filtration assisted by surface
tension (IFAST). The foundation of this technology is immiscible phase
filtration, using a magnet to draw paramagnetic particle (PMP)-bound
analyte through an immiscible barrier (oil or organic solvent) that
separates an aqueous sample from an aqueous eluting buffer. The immiscible
barrier functions to remove unbound proteins via exclusion rather
than dilutive washing used in traditional isolation methods. We identified
31 interactors from plasma, of which only seven were previously known
to interact with Fn. Furthermore, five proteins were identified to
interact with 70k-Fn from platelet lysate, of which one was previously
known. These results demonstrate that IFAST offers advantages for
proteomic studies of interacting molecules in that the technique requires
small sample volumes, can be done with high enough throughput to sample
multiple interaction conditions, and is amenable to exploratory mass
spectrometric and confirmatory immuno-blotting read-outs
Directions in cardiovascular medical: the renin system in the diagnosis of hypertension
+51hlm.;28c
Transcutaneous treatment with vetdrop® sustains the adjacent cartilage in a microfracturing joint defect model in sheep
The significance of the adjacent cartilage in cartilage defect healing is not yet completely understood. Furthermore, it is unknown if the adjacent cartilage can somehow be influenced into responding after cartilage damage. The present study was undertaken to investigate whether the adjacent cartilage can be better sustained after microfracturing in a cartilage defect model in the stifle joint of sheep using a transcutaneous treatment concept (Vetdrop®).
Carprofen and chito-oligosaccharids were added either as single components or as a mixture to a vehicle suspension consisting of a herbal carrier oil in a water-in-oil phase. This mixture was administered onto the skin with the aid of a specific applicator during 6 weeks in 28 sheep, allocated into 6 different groups, that underwent microfracturing surgery either on the left or the right medial femoral condyle. Two groups served as control and were either treated intravenously or sham treated with oxygen only. Sheep were sacrificed and their medial condyle histologically evaluated qualitatively and semi-quantitatively according to 4 different scoring systems (Mankin, ICRS, Little and O’Driscoll).
The adjacent cartilage of animals of group 4 treated transcutaneously with vehicle, chito-oligosaccharids and carprofen had better histological scores compared to all the other groups (Mankin 3.3±0.8, ICRS 15.7±0.7, Little 9.0±1.4). Complete defect filling was absent from the transcutaneous treatment groups.
The experiment suggests that the adjacent cartilage is susceptible to treatment and that the combination of vehicle, chitooligosaccharids and carprofen may sustain the adjacent cartilage during the recovery period