Synergy between paclitaxel plus an exogenous methyl donor in the suppression of murine demyelinating diseases

2007 ◽  
Vol 13 (5) ◽  
pp. 596-609 ◽  
Author(s):  
FG Mastronardi ◽  
H. Tsui ◽  
S. Winer ◽  
DD Wood ◽  
T. Selvanantham ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Combination Therapy ◽  
Clinical Signs ◽  
Demyelinating Diseases ◽  
Model Systems ◽  
Methyl Donor ◽  
Negative Balance ◽  
Vitro Model

Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol®) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously described combination of IFN-beta/ B12CN, whose clinical usefulness is transient because of IFN-neutralising antibodies, not observed (or expected) with the present drug combination. This report provides a mechanistic foundation for the development of a new therapeutic strategy in humans with MS. Multiple Sclerosis 2007; 13: 596-609. http://msj.sagepub.com

scholarly journals Imaging cell biology in live animals: Ready for prime time

2013 ◽  
Vol 201 (7) ◽  
pp. 969-979 ◽  
Author(s):  
Roberto Weigert ◽  
Natalie Porat-Shliom ◽  
Panomwat Amornphimoltham
Keyword(s):  
Cell Biology ◽  
Cancer Biology ◽  
In Vitro Model ◽  
Time Lapse ◽  
Living Cells ◽  
Model Systems ◽  
Prime Time ◽  
Vitro Model

Time-lapse fluorescence microscopy is one of the main tools used to image subcellular structures in living cells. Yet for decades it has been applied primarily to in vitro model systems. Thanks to the most recent advancements in intravital microscopy, this approach has finally been extended to live rodents. This represents a major breakthrough that will provide unprecedented new opportunities to study mammalian cell biology in vivo and has already provided new insight in the fields of neurobiology, immunology, and cancer biology.

Biological Responses of Fibroblasts to Cyclic Stretching: A Novel Culture Model Study

2000 ◽  
Author(s):  
James H.-C. Wang ◽  
David Stone ◽  
Fengyan Jia ◽  
Chris Celechovsky ◽  
Savio L.-Y. Woo
Keyword(s):  
Control Cell ◽  
Model Systems ◽  
Cell Alignment ◽  
Experimental Conditions ◽  
Cyclic Stretching ◽  
Biological Responses ◽  
Model Study ◽  
Vitro Model

Abstract Because of the advantage of better control of experimental conditions, in vitro model systems have been developed to examine the effects of mechanical loading on cells. Previous studies have shown that cyclic stretching causes cells to change orientation, proliferation and gene expression (Buck et al., 1980; Wang et al., 1995; Leung et al., 1976). However, one drawback of these model systems is that they are unable to control cell alignment and shape, and in addition, some provide heterogeneous strains to cells during stretching (See review by Schaffer, 1994). Consequently, cellular responses in these systems may not be similar to those in vivo. For example, tendon and ligament fibroblasts align with collagen fibers in vivo and are hence subjected to stretching along the tissue long axis. In contrast, in many existing systems, cells either randomly orient or orient away from the stretching direction.

Mechanism of glucose sensing in the small intestine

2003 ◽  
Vol 31 (6) ◽  
pp. 1140-1142 ◽  
Author(s):  
J. Dyer ◽  
S. Vayro ◽  
S.P. Shirazi-Beechey
Keyword(s):  
Glucose Transporter ◽  
Glucose Sensor ◽  
Cell Function ◽  
Glucose Sensing ◽  
Model Systems ◽  
Luminal Membrane ◽  
Sense And Respond ◽  
Vitro Model

Sensing nutrients is a fundamental task for all living cells. For most eukaryotic cells glucose is a major source of energy, having significant and varied effects on cell function. Interest in identifying mechanisms by which cells sense and respond to variations in glucose concentration has increased recently. The epithelial cells lining the intestinal tract are exposed, from the luminal domain, to an environment with continuous and massive fluctuations in the levels of dietary monosaccharides. Enterocytes therefore have to sense and respond to the significant changes in the levels of luminal sugars, and regulate the expression of the intestinal glucose transporter (Na+/glucose co-transporter, SGLT1) accordingly. Our data, using a combination of in vivo and in vitro model systems, suggest that glucose in the lumen of the intestine is sensed by a glucose sensor residing on the external face of the enterocyte luminal membrane. Glucose binds to the sensor and generates an intracellular signal leading to enhancement in the expression of SGLT1. The generated signal is independent of glucose metabolism and is likely to operate via a G-protein-coupled receptor and cAMP/protein kinase A signalling cascade.

scholarly journals Author Correction: The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nagasuryaprasad Kotikalapudi ◽  
Samuel Joshua Pragasam Sampath ◽  
Sinha Sukesh Narayan ◽  
Bhonde R. ◽  
Harishankar Nemani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
In Vitro Model ◽  
Model Systems ◽  
Mesenchymal Stem Cell Therapy ◽  
Preclinical Diabetes ◽  
Vitro Model

Morphological effects of sulfur mustard on a human skin equivalent

1991 ◽  
Vol 49 ◽  
pp. 78-79
Author(s):  
J.P. Petrali ◽  
S.B. Oglesby ◽  
T.A. Justus
Keyword(s):  
Human Skin ◽  
Sulfur Mustard ◽  
Athymic Nude Mouse ◽  
Skin Equivalent ◽  
Model Systems ◽  
Cells In Culture ◽  
Vitro Model ◽  
Human Skin Equivalent

We have previously reported morphological correlates of sulfur mustard (HD) toxicity in several model systems: the human skin grafted athymic nude mouse; the hairless guinea pig; and human cells in culture. We are now describing HD effects in a human skin equivalent, TESTSKIN®, and comparing these effects with those already reported for animal models and cells in culture. The human skin equivalent (HSE) is used here as an organotypic in vitro model system to bridge the knowledge gap between HD effects in monotypic cells in culture and animal in vivo effects. Additionally, HSE allowed study of HD toxicity which circumvented the concern of using human biopsied tissue.

scholarly journals Study of the l-Phenylalanine Ammonia-Lyase Penetration Kinetics and the Efficacy of Phenylalanine Catabolism Correction Using In Vitro Model Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 383
Author(s):  
Lyubov Dyshlyuk ◽  
Stanislav Sukhikh ◽  
Svetlana Noskova ◽  
Svetlana Ivanova ◽  
Alexander Prosekov ◽  
...  
Keyword(s):  
Phenylalanine Ammonia Lyase ◽  
In Vitro Model ◽  
High Efficiency ◽  
Tumor Regression ◽  
Liver Cells ◽  
Model Systems ◽  
In Vivo Studies ◽  
Vitro Model

The kinetics of l-phenylalanine ammonia-lyase (PAL) penetration into the monolayer of liver cells after its release from capsules was studied. The studies showed the absence of the effect of the capsule shell based on plant hydrocolloids on the absorption of l-phenylalanine ammonia-lyase in systems simulating the liver surface. After 120 min of incubation, in all variants of the experiment, from 87.0 to 96.8% of the enzyme penetrates the monolayer of liver cells. The combined analysis of the results concludes that the developed encapsulated form of l-phenylalanine ammonia-lyase is characterized by high efficiency in correcting the disturbed catabolism of phenylalanine in phenylketonuria, which is confirmed by the results of experiments carried out on in vitro model systems. PAL is approved for the treatment of adult patients with phenylketonuria. The encapsulated l-phenylalanine ammonia-lyase form can find therapeutic application in the phenylketonuria treatment after additional in vitro and in vivo studies, in particular, the study of preparation safety indicators. Furthermore, it demonstrated high efficacy in tumor regression and the treatment of tyrosine-related metabolic disorders such as tyrosinemia. Several therapeutically valuable metabolites biosynthesized by PAL via its catalytic action are included in food supplements, antimicrobial peptides, drugs, amino acids, and their derivatives. PAL, with improved pharmacodynamic and pharmacokinetic properties, is a highly effective medical drug.

scholarly journals Liver-derived cell lines from cavefish Astyanax mexicanus as an in vitro model for studying metabolic adaptation

2022 ◽  
Author(s):  
Jaya Krishnan ◽  
Yan Wang ◽  
Olga Kenzior ◽  
Huzaifa Hassan ◽  
Luke Olsen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cost Effective ◽  
Science Research ◽  
Model Systems ◽  
Metabolic Adaptation ◽  
Astyanax Mexicanus ◽  
Surface Dwelling ◽  
Vitro Model

Cell lines have become an integral resource and tool for conducting biological experiments ever since the Hela cell line was first developed (1). They not only allow detailed investigation of molecular pathways but are faster and more cost-effective than most in vivo approaches. The last decade saw many emerging model systems strengthening basic science research. However, lack of genetic and molecular tools in these newer systems pose many obstacles. Astyanax mexicanus is proving to be an interesting new model system for understanding metabolic adaptation. To further enhance the utility of this system, we developed liver-derived cell lines from both surface-dwelling and cave-dwelling morphotypes. In this study, we provide detailed methodology of the derivation process along with a comprehensive biochemical and molecular characterization of the cell lines, which reflects key metabolic traits of cavefish adaptation. We anticipate these cell lines to become a useful resource for the Astyanax community as well as researchers investigating fish biology, comparative physiology, and metabolism.

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