Impairment of vitamin e intestinal secretion in primary hypobetalipoproteinemias: mechanistics studies in a cell models

2020 ◽  
Vol 40 ◽  
pp. 415-416
Author(s):  
C. Bordat ◽  
M. Nowicki ◽  
C. Halimi ◽  
E. Reboul ◽  
N. Peretti
Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 121 ◽  
Author(s):  
Brian T. Burgess ◽  
Abigail M. Anderson ◽  
J. Robert McCorkle ◽  
Jianrong Wu ◽  
Frederick R. Ueland ◽  
...  

Objective: Despite the promise of PARP inhibitors (PARPi) for treating BRCA1/2 mutated ovarian cancer (OC), drug resistance invariably develops. We hypothesized rationale drug combinations, targeting key molecules in DNA repair pathways and the cell cycle may be synergistic and overcome acquired PARPi resistance. Methods: Drug sensitivity to PARPi alone and in combination with inhibitors of key DNA repair and cell cycle proteins, including ATR (VE-821), Chk1 (MK-8776), Wee1 (MK-1775), RAD51 (RI-1) was assessed in PARPi-sensitive (UWB1) and -resistant (UWB1-R) gBRCA1 mutant OC cell lines using a cell proliferation assay. The Bliss synergy model was used to estimate the two-drug combination effect and pharmacologic synergy (Bliss score ≥ 0) or antagonistic (Bliss score ≥ 0) response of the PARPi in combination with the inhibitors. Results: IC50 for olaparib alone was 1.6 ± 0.9 µM compared to 3.4 ± 0.6 µM (p = 0.05) for UWB1 and UWB1-R cells, respectively. UWB1-R demonstrated increased sensitivity to ATRi (p = 0.04) compared to UWB1. Olaparib (0.3–1.25 µM) and ATRi (0.8–2.5 µM) were synergistic with Bliss scores of 17.2 ± 0.2, 11.9 ± 0.6 for UWB1 and UWB1-R cells, respectively. Olaparib (0.3–1.25 µM) and Chk1i(0.05–1.25 µM) were synergistic with Bliss scores of 8.3 ± 1.6, 5.7 ± 2.9 for UWB1 and UWB1-R cells, respectively. Conclusions: Combining an ATRi or Chk1i with olaparib is synergistic in both PARPi-sensitive and -resistant BRCA1 mutated OC cell models, and are rationale combinations for further clinical development.


1965 ◽  
Vol 5 (01) ◽  
pp. 89-99
Author(s):  
S.M. Farouq Ali ◽  
C.D. Stahl

Abstract This investigation attempts to describe and simulate the alcohol displacement process by means of a cell model, as employed in chemical engineering practice. The proposed model is more simple than previously proposed models, and utilizes parameters chosen on a theoretical basis. The model successfully reproduced the formation of the stabilized bank and the breakthrough of alcohol, the latter depending on one of the model parameters, which may be correlated with the length of the porous medium. Moreover, the effects of the phase behavior of the liquid system involved, as observed in experimental studies, were reproduced. Several variations of the basic model were devised and tested on a digital computer. These included the cases in which:the actual value of fractional flow was used in cell-to-cell computations;the number of cells was varied within the same run; andincomplete rather than complete phase equilibrium was assumed within each cell. The proposed cell model clarifies the basic mechanism of the process. Detailed concentration profiles obtained for each cell, for instance, showed the mechanism of bank formation in relation to the phase behavior characteristics. The results obtained indicated a varying degree of phase equilibrium concommitant with changes in the velocities of the phases in an actual alcohol displacement. This condition was approximated by changing the number of cells during the simulation. Interesting information was obtained on the influence of path length on the efficiency of alcohol displacement, which has been the subject of some controversy. Certain limitations preclude the use of the proposed model as a substitute for experimental studies. The results obtained were, nevertheless, of value in interpreting the experimental results. Introduction During recent years considerable effort has been directed toward an understanding of alcohol displacement, the process whereby oil and water are recovered from a porous medium by the continuous injection of a solvent. The complex nature of the physical process involved has so far defied a complete mathematical treatment. Other methods of approach, amounting to an overall material balance, have been proposed, yielding useful information on certain aspects of the process. Taber et al, in particular, defined the displacement mechanism in terms of the phase behavior of the alcohol-oil-brine system involved. Wachmann reported a mathematical treatment of alcohol displacement subject to certain simplifying assumptions. Donohue proposed the use of a "cell model" for simulating alcohol displacement. The nature of the assumptions involved limited the utility of the model. The present work attempts to examine the variables involved in the simulation of alcohol displacement and discusses several possible versions of the basic cell model. Under certain conditions the model results are similar to the experimental results. In particular, the spontaneous formation of the stabilized bank and the effects of the system phase behavior were successfully reproduced. PREVIOUS WORK ON CELL MODELS Cell models and the theoretical plate concept are often used in solving chemical engineering problems in which an explicit mathematical solution may be difficult or impossible to obtain. Examples of such applications occur in distillation, gas-liquid chromatography, reactor technology, absorption, etc. In petroleum engineering, such a model was used by Attra to describe non-equilibrium gas drive, and by Higgins and Leighton to calculate sweep efficiency in water flooding. Aris and Amundsen pointed out the equivalence between the diffusion model and perfectly mixed cells connected in series. SPEJ P. 89ˆ


2021 ◽  
Author(s):  
Brie Sorrenson ◽  
Waruni C Dissanayake ◽  
Fengyun Hu ◽  
Kate L Lee ◽  
Peter R Shepherd

The presence of adherens junctions and the associated protein β-catenin are requirements for the development of glucose stimulated insulin secretion (GSIS) in β-cells. Evidence indicates that modulation of β-catenin function in response to changes in glucose levels can modulate the levels of insulin secretion from β-cells but the role of β-catenin phosphorylation in this process has not been established. We find that a Ser552Ala version of β-catenin attenuates glucose stimulated insulin secretion indicating a functional role for Ser552 phosphorylation of β-catenin in insulin secretion. This is associated with alterations F/G actin ratio  but not  transcriptional activity of β-catenin.   Both glucose and GLP-1 stimulated phosphorylation of the serine 552 residue on β-catenin.  We investigated the possibility that an EPAC-PAK1 pathway might be involved in this phosphorylation event.  We find that reduction in PAK1 levels using siRNA attenuates both glucose and GLP-1 stimulated phosphorylation of β-catenin Ser552 and the effects of these on insulin secretion in β-cell models. Further, both the EPAC inhibitor ESI-09 and the PAK1 inhibitor IPA3 do the same in both β-cell models and mouse islets. Together this identifies phosphorylation of β-catenin at Ser552 as part of a cell signalling mechanism linking nutrient and hormonal regulation of β-catenin to modulation of  insulin secretory capacity of β-cells and indicates this phosphorylation event is regulated downstream of EPAC and PAK1 in β-cells.


Polymers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1847
Author(s):  
Pooyan Makvandi ◽  
Caterina Caccavale ◽  
Francesca Della Sala ◽  
Stefania Zeppetelli ◽  
Rosanna Veneziano ◽  
...  

Hyaluronic acid (HA) promotes wound healing, and, accordingly, formulations based on HA have been widely used in regenerative medicine. In addition, naturally derived compounds, e.g., plant-based extracts and vitamin E, have exhibited antioxidant activity. In this study, a formulation containing hyaluronic acid, vitamin E, raspberry extract, and green tea was developed for potential topical applications, targeting wound healing. Rheological analysis was performed along with antioxidant and biological studies. The rheological characterization showed that the HA-based formulation is a thixotropic platform and possesses higher mechanical properties than the control formulation. To evaluate the wound healing potential of the formulation, an in vitro “wound healing” assay was carried out using human derived fibroblasts (HDF) with a cell-free gap on the tissue culture dish. The formulation showed better wound healing ability than the control formulation.


1933 ◽  
Vol 17 (2) ◽  
pp. 211-235 ◽  
Author(s):  
Lewis G. Longsworth

The differential equations which describe the simultaneous diffusion of water and a salt in a cell model have been formulated and solved. The equations have been derived from the general laws which describe diffusion processes, thereby furnishing a physical interpretation for the constants which enter into the theory. The theoretical time curves for the two diffusing substances are in good agreement with the experimentally determined curves and accurately reproduce all of the essential characteristics of the experiment.


2019 ◽  
Vol 15 (3) ◽  
pp. 215-224
Author(s):  
Mohammad Farnush

Background:: Various models are used for brain tumors modeling. To our knowledge, no earlier work has been done on modeling the heterogeneous brain tumor that causes dizziness. However, specifying a cell using a model is not new. Unlike all earlier works in this regard, which consider analog or analog-CPU computers in the cell model, the model presented in this work fully utilizes processor computers. Materials and Methods:: The purpose of this study is to offer a comprehensive approach for heterogeneous modeling of brain tumor cells. The model uses a brain tumor cell in Matlab and Simulink 3D software. Two heterogeneous models are presented for brain tumor cells: the imagebased cell model and computer-generated cell model. The image-based cell model is obtained through the figure altering on X-ray or ocular figures by recognizing the dissimilar states in the tumors. Results:: The computer-generated cell model works based on locating computer produced aggregate cells into tumors. Some subdivisions for both the image-based and computer-generated cell models are presented as well. Conclusion:: The positive and negative points of the image-based cell models and computergenerated cell models some scientific advices are presented in this work. Generally, the imagebased cell models could offer analytical facts for each state, but they are expensive and timeconsuming; besides, their performance is heavily influenced by deformation techniques. The computer-generated cell model, on the other hand, provides a higher cost of production and simplicity, but its main contribution is the overall performance and accuracy.


1993 ◽  
Vol 85 (5) ◽  
pp. 629-635 ◽  
Author(s):  
K. J. Lindley ◽  
D. P. R. Muller ◽  
P. J. Milla

1. A vicious cycle of malabsorption and malnutrition has been implicated in the pathogenesis of protracted diarrhoeal disease in infancy. Vitamin E deficiency is common in malnourished infants with protracted diarrhoea. We have studied the effects of chronic vitamin E deficiency on small-inestinal secretion and absorption in the rat. 2. Weanling rats were fed vitamin E-sufficient or -deficient diets for 21 weeks. Jejunal function was studied in vitro in an Ussing chamber after this period. 3. Steady-state isotopic flux experiments in unstimulated tissues demonstrated net Na+ and Cl−secretion in vitamin E-deficient jejuna but net Na+ and Cl− absorption in vitamin E-sufficient jejuna. 4. Basal intestinal short-circuit current was the same in both groups. 5. Cyclic nucleotide and maximal non-neuronal acetylcholine-mediated electrogenic secretion were increased in vitamin E-deficient jejuna. 6. Exogenous 5-hydroxytryptamine (serotonin) induced a smaller increment in electrogenic secretion in vitamin E-deficient jejuna. 7. Vitamin E-deficient jejuna were less responsive to exogenous noradrenaline, resulting in a smaller α2-adrenergic-mediated decrease in intestinal short-circuit current. 8. Fasting for 72 h produced a greater increment in intestinal short-circuit current in vitamin E-deficient jejuna. 9. Chronic vitamin E deficiency is prosecretory in the small intestine and may predispose to the perpetuation of protracted diarrhoeal diseases.


Author(s):  
M. Arif Hayat

Although it is recognized that niacin (pyridine-3-carboxylic acid), incorporated as the amide in nicotinamide adenine dinucleotide (NAD) or in nicotinamide adenine dinucleotide phosphate (NADP), is a cofactor in hydrogen transfer in numerous enzyme reactions in all organisms studied, virtually no information is available on the effect of this vitamin on a cell at the submicroscopic level. Since mitochondria act as sites for many hydrogen transfer processes, the possible response of mitochondria to niacin treatment is, therefore, of critical interest.Onion bulbs were placed on vials filled with double distilled water in the dark at 25°C. After two days the bulbs and newly developed root system were transferred to vials containing 0.1% niacin. Root tips were collected at ¼, ½, 1, 2, 4, and 8 hr. intervals after treatment. The tissues were fixed in glutaraldehyde-OsO4 as well as in 2% KMnO4 according to standard procedures. In both cases, the tissues were dehydrated in an acetone series and embedded in Reynolds' lead citrate for 3-10 minutes.


Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.


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