Advances in the use of 3D colorectal cancer models for novel drug discovery.

Introduction: Colorectal cancer (CRC) is one of the most common and deadly tumors worldwide. CRC and models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. However, two-dimensional (2D) culture systems are considered too simple and do not represent the complex nature of the human tumor.

Neurochemical Modifications in the Hippocampus, Cortex and Hypothalamus of Mice Exposed to Long-Term High-Fat Diet.

Metabolic syndrome and diabetes impact brain function and metabolism. While it is well established that rodents exposed to diets rich in saturated fat develop brain dysfunction, contrasting results abound in the literature, likely as result of exposure to different high-fat diet (HFD) compositions and for varied periods of time. In the present study, we investigated alterations of hippocampal-dependent spatial memory by measuring Y-maze spontaneous alternation, metabolic profiles of the hippocampus, cortex and hypothalamus by H magnetic resonance spectroscopy (MRS), and levels of proteins specific to synaptic and glial compartments in mice exposed for 6 months to different amounts of fat (10, 45, or 60% of total energy intake).

Non-invasive diagnosis and metabolic consequences of congenital portosystemic shunts in C57BL/6 J mice.

This study demonstrates the suitability of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) for the imaging of congenital portosystemic shunts (PSS) in mice, a vascular abnormality in which mesenteric blood bypasses the liver and is instead drained directly to the systemic circulation. The non-invasive diagnosis performed in tandem with other experimental assessments permits further characterization of liver, whole-body and brain metabolic defects associated with PSS. Magnetic resonance measurements were performed in a 26-cm, horizontal-bore, 14.

Increased hepatic fatty acid polyunsaturation precedes ectopic lipid deposition in the liver in adaptation to high-fat diets in mice.

Objective: We monitored hepatic lipid content (HLC) and fatty acid (FA) composition in the context of enhanced lipid handling induced by a metabolic high-fat diet (HFD) challenge and fasting.

Materials And Methods: Mice received a control diet (10% of kilocalories from fat, N = 14) or an HFD (45% or 60% of kilocalories from fat, N = 10 and N = 16, respectively) for 26 weeks. A subset of five mice receiving an HFD (60% of kilocalories from fat) were switched to the control diet for the final 7 weeks.

Sexual dimorphism in hepatic lipids is associated with the evolution of metabolic status in mice.

Ectopic lipid accumulation in the liver is implicated in metabolic disease in an age- and sex-dependent manner. The role of hepatic lipids has been well established within the scope of metabolic insults in mice, but has been insufficiently characterized under standard housing conditions, where age-related metabolic alterations are known to occur. We studied a total of 10 male and 10 female mice longitudinally.

Technical and experimental features of Magnetic Resonance Spectroscopy of brain glycogen metabolism.

In the brain, glycogen is a source of glucose not only in emergency situations but also during normal brain activity. Altered brain glycogen metabolism is associated with energetic dysregulation in pathological conditions, such as diabetes or epilepsy. Both in humans and animals, brain glycogen levels have been assessed non-invasively by Carbon-13 Magnetic Resonance Spectroscopy (C-MRS) in vivo.

Characterization of hepatic fatty acids in mice with reduced liver fat by ultra-short echo time (1)H-MRS at 14.1 T in vivo.

Alterations in the hepatic lipid content (HLC) and fatty acid composition are associated with disruptions in whole body metabolism, both in humans and in rodent models, and can be non-invasively assessed by (1)H-MRS in vivo. We used (1)H-MRS to characterize the hepatic fatty-acyl chains of healthy mice and to follow changes caused by streptozotocin (STZ) injection. Using STEAM at 14.

Oral administration of peptides and proteins: nanoparticles and cyclodextrins as biocompatible delivery systems.

This review discusses drawbacks to peptide and protein oral formulations related to these drugs' chemical and physical instability. Means used to overcome such limitations are mentioned and discussed in parallel with manufacturing considerations, metabolism, absorption mechanisms and the efflux systems that peptides and proteins experience as they travel through the gastrointestinal tract. Special focus is given to the use of delivery systems based on nanoparticles and cyclodextrins.