The impact of emulsion droplet size on in vitro lipolysis rate and in vivo plasma uptake kinetics of triglycerides and vitamin D3 in rats

2021 ◽  
Author(s):  
Morten J. Dille ◽  
Tuna Baydin ◽  
Kåre A. Kristiansen ◽  
Kurt I. Draget
Keyword(s):  
Vitamin D ◽  
Droplet Size ◽  
Vitamin D3 ◽  
Uptake Kinetics ◽  
Emulsion Droplet ◽  
In Vitro Lipolysis ◽  
The Impact ◽  
Kinetics Of

Emulsions with smaller droplets are more rapidly lipolyzed in the intestine, resulting in increased uptake to plasma of triglycerides. However, the uptake of vitamin D3 from the same emulsions is not significantly affected by droplet size.

scholarly journals Dietary compounds as potential modulators of microRNA expression in psoriasis

2019 ◽  
Vol 10 ◽  
pp. 204062231986480 ◽  
Author(s):  
Hristina Kocic ◽  
Giovanni Damiani ◽  
Bojana Stamenkovic ◽  
Michael Tirant ◽  
Andrija Jovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Omega 3 ◽  
Experimental Conditions ◽  
Keratinocyte Proliferation ◽  
Methyl Donors ◽  
Beneficial Effects ◽  
Small Noncoding Rnas ◽  
The Impact

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between ‘good and bad’ miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other ‘omics’, may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.

scholarly journals The calcium ionophore A23187 is a potent stimulator of the vitamin D3-25 hydroxylase in hepatocytes isolated from normocalcaemic vitamin D-depleted rats

1988 ◽  
Vol 255 (1) ◽  
pp. 91-97 ◽  
Author(s):  
N Benbrahim ◽  
C Dubé ◽  
S Vallieres ◽  
M Gascon-Barré
Keyword(s):  
Vitamin D ◽  
Enzyme Activity ◽  
Serum Calcium ◽  
Vitamin D3 ◽  
Ionophore A23187 ◽  
Potent Stimulator ◽  
Group 2 ◽  
Group 1

The role played by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and/or by calcium on the C-25 hydroxylation of vitamin D3 (D3) was studied in hepatocytes isolated from D-depleted rats which were divided into four treatment groups: Group 1 served as controls, Group 2 received calcium gluconate, Groups 3 and 4 were infused with 1,25(OH)2D3 at 7 and 65 pmol/24 h x 7 days respectively. The treatments normalized serum calcium in all but the controls which remained hypocalcaemic, while serum 1,25(OH)2D3 remained low in Groups 1 and 2 but increased to physiologic and supraphysiologic levels in Groups 3 and 4. The data show that basal D3-25 hydroxylase activities were not significantly affected by any of the treatments. Addition of CaCl2, EGTA, or Quin-2 in vitro revealed that relative to basal values, EGTA strongly inhibited the enzyme activity in all groups (P less than 0.0001), except in G 1; Quin-2 and CaCl2 had no significant effect on the activity of the enzyme in any of the groups. Addition of 1,25(OH)2D3 or A23187 in vitro in the presence of CaCl2 revealed that 1,25(OH)2D3 did not significantly affect enzyme activity, while A23187 was found to stimulate its activity in vitamin D-depleted animals, but most specifically in Group 2 (P less than 0.001); low serum calcium (Group 1) dampened (P less than 0.01), and 1,25(OH)2D3 treatment in vivo totally blunted (P less than 0.001) the response to A23187. The data suggest that 1,25(OH)2D3 supplementation in vivo has per se little or no effect on the basal D3-25 hydroxylase activity. The data show, however, that the magnitude of the response to various challenges in vitro is greatly influenced by the conditioning in vivo of the animals. They also show that A23187 can be a potent stimulator of the enzyme activity, which allowed us to demonstrate a significant reserve for the C-25 hydroxylation of D3 which is well expressed in hepatocytes obtained from D-depleted calcium-supplemented rats.

scholarly journals Vitamin D as a Primer for Oncolytic Viral Therapy in Colon Cancer Models

2020 ◽  
Vol 21 (19) ◽  
pp. 7326
Author(s):  
Sang-In Kim ◽  
Shyambabu Chaurasiya ◽  
Anthony K. Park ◽  
Seonah Kang ◽  
Jianming Lu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Vitamin D ◽  
Human Colon ◽  
Oncolytic Viruses ◽  
Human Colon Cancer ◽  
Oncolytic Viral Therapy ◽  
Viral Therapy ◽  
The Impact

Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D analogue as an adjunct to oncolytic viral therapy for colon cancer. While vitamin D (VD) has historically been viewed as anti-viral, our in vitro investigations using human colon cancer cell lines showed that VD does not directly inhibit replication of recombinant chimeric poxvirus CF33. VD did restrict growth in HT29 but not HCT116 human colon cancer cells. In vivo investigations using HCT116 and HT29 xenograft models of colon cancer demonstrated that a VD analogue, calcipotriol, was additive with CF33-based viral therapy in VD-responsive HT29 but not in HCT116 tumors. Analyses of RNA-sequencing and gene expression data demonstrated a downregulation in the Jak-STAT signaling pathway with the addition of VD to viral therapy in HT29 models suggesting that the anti-inflammatory properties of VD may enhance the effects of viral therapy in some models. In conclusion, VD may prime oncolytic viral therapy in certain colon cancers.

scholarly journals A mathematical investigation into the uptake kinetics of nanoparticles in vitro

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254208
Author(s):  
Hannah West ◽  
Fiona Roberts ◽  
Paul Sweeney ◽  
Simon Walker-Samuel ◽  
Joseph Leedale ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Differential Equations ◽  
Mixed Culture ◽  
Uptake Kinetics ◽  
Multiphase System ◽  
Chemotherapy Drugs ◽  
Culture Model ◽  
The Impact ◽  
Kinetics Of

Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs. Here we develop a mathematical model to simulate the uptake of polymersomes via endocytosis, a process by which polymersomes bind to the cell surface before becoming internalised by the cell where they then break down, releasing their contents which could include chemotherapy drugs. We focus on two in vitro configurations relevant to the testing and development of cancer therapies: a well-mixed culture model and a tumour spheroid setup. Our mathematical model of the well-mixed culture model comprises a set of coupled ordinary differential equations for the unbound and bound polymersomes and associated binding dynamics. Using a singular perturbation analysis we identify an optimal number of ligands on the polymersome surface which maximises internalised polymersomes and thus intracellular chemotherapy drug concentration. In our mathematical model of the spheroid, a multiphase system of partial differential equations is developed to describe the spatial and temporal distribution of bound and unbound polymersomes via advection and diffusion, alongside oxygen, tumour growth, cell proliferation and viability. Consistent with experimental observations, the model predicts the evolution of oxygen gradients leading to a necrotic core. We investigate the impact of two different internalisation functions on spheroid growth, a constant and a bond dependent function. It was found that the constant function yields faster uptake and therefore chemotherapy delivery. We also show how various parameters, such as spheroid permeability, lead to travelling wave or steady-state solutions.

scholarly journals Effect of 1α,25(OH)2 Vitamin D3 in Mutant P53 Glioblastoma Cells: Involvement of Neutral Sphingomyelinase1

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3163
Author(s):  
Samuela Cataldi ◽  
Cataldo Arcuri ◽  
Andrea Lazzarini ◽  
Irina Nakashidze ◽  
Francesco Ragonese ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Survival Rates ◽  
P53 Mutation ◽  
Surgical Approaches ◽  
Mutant P53 ◽  
Glioblastoma Cells ◽  
Ceramide Content

Glioblastoma is one the most aggressive primary brain tumors in adults, and, despite the fact that radiation and chemotherapy after surgical approaches have been the treatments increasing the survival rates, the prognosis of patients remains poor. Today, the attention is focused on highlighting complementary treatments that can be helpful in improving the classic therapeutic approaches. It is known that 1α,25(OH)2 vitamin D3, a molecule involved in bone metabolism, has many serendipidy effects in cells. It targets normal and cancer cells via genomic pathway by vitamin D3 receptor or via non-genomic pathways. To interrogate possible functions of 1α,25(OH)2 vitamin D3 in multiforme glioblastoma, we used three cell lines, wild-type p53 GL15 and mutant p53 U251 and LN18 cells. We demonstrated that 1α,25(OH)2 vitamin D3 acts via vitamin D receptor in GL15 cells and via neutral sphingomyelinase1, with an enrichment of ceramide pool, in U251 and LN18 cells. Changes in sphingomyelin/ceramide content were considered to be possibly responsible for the differentiating and antiproliferative effect of 1α,25(OH)2 vitamin D in U251 and LN18 cells, as shown, respectively, in vitro by immunofluorescence and in vivo by experiments of xenotransplantation in eggs. This is the first time 1α,25(OH)2 vitamin D3 is interrogated for the response of multiforme glioblastoma cells in dependence on the p53 mutation, and the results define neutral sphingomyelinase1 as a signaling effector.

The influence of lipid droplet size on the oral bioavailability of vitamin D2encapsulated in emulsions: an in vitro and in vivo study

2017 ◽  
Vol 8 (2) ◽  
pp. 767-777 ◽  
Author(s):  
L. Salvia-Trujillo ◽  
B. Fumiaki ◽  
Y. Park ◽  
D. J. McClements
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Health Effects ◽  
Droplet Size ◽  
Oral Bioavailability ◽  
Functional Foods ◽  
Adverse Health Effects ◽  
Lipid Droplet Size

Vitamin D deficiency is prevalent in some populations leading to adverse health effects, and therefore there is a need to supplement functional foods and beverages with this important micronutrient.

scholarly journals Impact of real-time shedding on binding kinetics of membrane-remaining L-selectin to PSGL-1

2019 ◽  
Vol 316 (5) ◽  
pp. C678-C689 ◽  
Author(s):  
Shuang Peng ◽  
Shen-Bao Chen ◽  
Lin-Da Li ◽  
Chun-Fang Tong ◽  
Ning Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Real Time ◽  
Jurkat Cells ◽  
Binding Kinetics ◽  
Time Dependent ◽  
Intact Cells ◽  
The Impact ◽  
Kinetics Of

L-selectin shedding induced by various cytokines is crucial in activating neutrophils (PMNs) in inflammatory cascade. While the real-time shedding in vivo lasts ~10 min after PMN activation, the impact of time-dependent shedding on binding kinetics of membrane-remaining L-selectins to its ligands is poorly understood at transient or steady state. Here, we developed an in vitro L-selectin shedding dynamics approach, together with competitive assays of cell adhesion, and proposed a theoretical model for quantifying the impact of real-time shedding on the binding kinetics of membrane-remaining L-selectins to P-selectin glycoprotein ligand-1 (PSGL-1). Our data indicated that the extent of L-selectin shedding on PMA activation is higher, but the terminating time is longer for Jurkat cells than those for human PMNs. Meanwhile, fMLF or IL-8 stimulation yields the longer terminating time than that on PMA stimulation but results in a similar shedding extent for PMNs. L-selectin shedding reduces L-selectin-PSGL-1-mediated cell adhesion in three ways: decreasing membrane-anchored L-selectins, increasing soluble L-selectins competitively binding to ligands, and presenting conformational alteration of membrane-remaining L-selectins themselves. Compared with those on intact cells, the binding affinities of membrane-remaining L-selectin-PSGL-1 pairs were all enhanced at initial and lowered at the late shedding phase for both PMN and Jurkat cells even with varied transition time points. The rolling velocities of both PMNs and Jurkat cells were increased following mechanically or biochemically induced shedding of L-selectin under shear flow. These findings help to further our understanding of the function of time-dependent L-selectin shedding during the inflammation cascade.

scholarly journals Vitamin D Incorporation in Foods: Formulation Strategies, Stability, and Bioaccessibility as Affected by the Food Matrix

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1989
Author(s):  
Vera Lavelli ◽  
Paolo D’Incecco ◽  
Luisa Pellegrino
Keyword(s):  
Vitamin D ◽  
Skin Pigmentation ◽  
Industrial Processing ◽  
Global Health Issue ◽  
Free Vitamin D ◽  
In Vitro Bioaccessibility ◽  
Processing And Storage ◽  
The Impact

Inadequate intake of vitamin D is a global health issue related to severe diseases, mainly involving subjects with dark skin pigmentation, patients affected by malnutrition, malabsorption syndromes, or obesity, and elderly people. Some foods fortified with vitamin D have been tested in vivo, but fortification strategies with a global outreach are still lacking. This review is focused on food fortification with vitamin D, with the aim to collect information on (a) formulation strategies; (b) stability during processing and storage; and (c) in vitro bioaccessibility. Approaches to add vitamin D to various foods were analyzed, including the use of free vitamin D, vitamin D loaded in simple and double nanoemulsions, liposomes, casein micelles, and protein nanocapsules. Numerous studies were reviewed to elucidate the impact of food technologies on vitamin D’s stability, and mechanisms that lead to degradation were identified—namely, acid-catalyzed isomerization, radical-induced oxidation, and photo-oxidation. There is, however, a lack of kinetic data that allow for the prediction of vitamin D’s stability under industrial processing conditions. The roles that lipids, proteins, fibers, and antioxidants play in vitamin bioaccessibility have been clarified in various studies, while future needs include the design of specific food matrices that simultaneously achieve a balance between the long-term stability, bioaccessibility and, ultimately, in vivo functionality of vitamin D.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

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