Generation of Inducible BCL11B Knockout in TAL1/LMO1 Transgenic Mouse T Cell Leukemia/Lymphoma Model.

The B-cell CLL/lymphoma 11B gene (BCL11B) plays a crucial role in T-cell development, but its role in T-cell malignancies is still unclear. To study its role in the development of T-cell neoplasms, we generated an inducible BCL11B knockout in a murine T cell leukemia/lymphoma model. Mice, bearing human oncogenes TAL BHLH Transcription Factor 1 (TAL1; SCL) or LIM Domain Only 1 (LMO1), responsible for T-cell acute lymphoblastic leukemia (T-ALL) development, were crossed with BCL11B floxed and with CRE-ER/lox mice. The mice with a single oncogene BCL11Bflox/floxCREtg/tgTAL1tg or BCL11Bflox/floxCREtg/tgLMO1tg were healthy, bred normally, and were used to maintain the mice in culture. When crossed with each other, >90% of the double transgenic mice BCL11Bflox/floxCREtg/tgTAL1tgLMO1tg, within 3 to 6 months after birth, spontaneously developed T-cell leukemia/lymphoma. Upon administration of synthetic estrogen (tamoxifen), which binds to the estrogen receptor and activates the Cre recombinase, the BCL11B gene was knocked out by excision of its fourth exon from the genome. The mouse model of inducible BCL11B knockout we generated can be used to study the role of this gene in cancer development and the potential therapeutic effect of BCL11B inhibition in T-cell leukemia and lymphoma.

Effects of Bitter Melon and a Chromium Propionate Complex on Symptoms of Insulin Resistance and Type 2 Diabetes in Rat Models.

Trivalent chromium (Cr) and bitter melon (Momordica charantia L., BM) have been shown to independently interact with the insulin signaling pathway leading to improvements in the symptoms of insulin resistance and diabetes in some animal models and human subjects. The aim of this study was to examine whether the combination of the two nutritional supplements could potentially have additive effects on treating these conditions in high-fat-fed streptozotocin (STZ)-induced diabetic rats. The experiment was conducted with 110 male Wistar rats divided into eleven groups and fed either a control or high-fat diet for 7 weeks. Half of the rats on the high-fat diet were injected with STZ (30 mg/kg body mass) to induce diabetes. The high-fat (HF) diets were then supplemented with a combination of Cr (as chromium(III) propionate complex, Cr3: either 10 or 50 mg Cr/kg diet) and bitter melon (lyophilized whole fruit: either 10 or 50 g/kg diet) for 6 weeks. After termination of the experiment, blood and internal organs were harvested for blood biochemical, hematological, and mineral (Cr) analyses using appropriate analytical methods. It was found that neither Cr(III) nor BM was able to significantly affect blood indices in HF and diabetic rats, but BM tended to improve body mass gain, blood glucose, and LDL cholesterol values, but decreased Cr content in the liver and kidneys of the Cr-co-supplemented type 2 diabetic model of rats. Supplementary Cr(III) had no appreciable effect on glucose and lipid metabolism in high-fat-fed STZ-induced diabetic rats. Supplementary BM fruit powder had some observable effects on body mass of high-fat-fed rats; these effects seem to be dampened when BM was co-administered with Cr. Cr(III) and BM appear to act as nutritional antagonists when both administered in food, probably due to binding of Cr by the polyphenol-type compounds present in the plant material. Graphical Abstract.

Protein and folic acid content in the maternal diet determine lipid metabolism and response to high-fat feeding in rat progeny in an age-dependent manner.

Maternal diet during gestation can exert a long-term effect on the progeny's health by programming their developmental scheme and metabolism. The aim of this study is to analyze the influence of maternal diet on lipid metabolism in 10- and 16-week-old rats. Pregnant dams were fed one of four diets: a normal protein and normal folic acid diet (NP-NF), a protein-restricted and normal folic acid diet (PR-NF), a protein-restricted and folic-acid-supplemented diet (PR-FS), or a normal protein and folic-acid-supplemented diet (NP-FS). We also tested whether prenatal nutrition determines the reaction of an organism to a postweaning high-fat diet. Blood biochemistry and biometrical parameters were evaluated. The expression patterns of PPARα, PPARγ, and LXRα in the liver and adipose tissue were examined by real-time PCR. In the 10-week-old, rats folic acid supplementation of the maternal diet was associated with reduced circulating glucose and total cholesterol concentrations (P < 0.01 and P < 0.001, respectively). Neither prenatal diets nor postnatal feeding affected blood insulin concentrations. In the 16-week-old rats, body weight, abdominal fat mass and central adiposity were reduced in the progeny of the folic acid-supplemented dams (P < 0.01, P < 0.001 and P < 0.01, respectively). Maternal protein restriction had no effect on biometry or blood biochemical parameters. Folic acid supplementation of the maternal diet was associated with reduced expression of PPARα, PPARγ, and LXRα in the liver (P < 0.001). Reduced protein content in the maternal diet was associated with increased PPARα mRNA level in the liver (P < 0.001) and reduced LXRα in adipose tissue (P < 0.01). PPARα and PPARγ transcription in the liver, as well as LXRα transcription in adipose tissue, was also dependent on interaction effects between prenatal and postnatal diet compositions. PPARγ transcription in the liver was correlated with the abdominal fat mass, body weight, and calorie intake, while PPARγ transcription in adipose tissue was correlated with reduced body weight and calorie intake. Total serum cholesterol concentration was correlated with LXRα transcription in the liver. Folic acid supplementation of the maternal diet may have favorable effects for lipid metabolism in the progeny, but these effects are modified by the postnatal diet and age. Furthermore, the expression of LXRα, PPARα, and PPARγ in the liver and adipose tissue largely depends on the protein and folic acid content in the maternal diet during gestation. However, the altered transcription profile of these key regulators of lipid metabolism does not straightforwardly explain the observed phenotype.

Discrepancy between clinical and histological effects of DHA supplementation in a rat model of pouchitis.

Docosahexaenoic acid (DHA) potentially modulates inflammatory processes. Therefore, the aim of this study was to determine the influence of DHA supplementation on the expression of intestinal inflammation and nutritional status in rats which have undergone restorative proctocolectomy. Twenty-four Wistar rats were operated. After the induction of pouchitis, animals were randomly divided into a control group (CG) and supplementation groups receiving respectively a semi-synthetic diet without or with DHA (in a lower or higher dose, respectively known as the lower dose, LD, and higher dose, HD, groups) for six weeks. Selected nutritional parameters were assessed. Histopathological and immunohistochemical analysis of pouch mucosa specimens was also performed. The effectiveness of feeding and quality of stools were significantly better in the HD group than in the CG. The intensity of inflammation (Moskovitz scale) was higher in HD and LD than in CG (p = 0.03 and p = 0.0006, respectively). Nevertheless, pouch adaptation (Laumonier scale) was more significant in LD than in CG (p = 0.007). On the other hand, tissue expression of IL-1α and IL-10 was higher in HD and LD than in CG (IL-1α, p = 0.009 and p = 0.05, respectively; IL-10, p = 0.04 for both). DHA supplementation has no impact on body weight gain. Yet it seems that it may improve the effectiveness of nutrition and stool quality in rats which have undergone restorative proctocolectomy. Simultaneously, it increases the intensity of pouch adaptation and inflammation. The specificity of observed changes is not clear. However, it may imply potential modulation of inflammatory processes of pouch mucosa.

Inulin supplementation in rat model of pouchitis.

Available data indicates potential effectiveness of prebiotic therapy in alleviating inflammation and prolonging the remission in inflammatory bowel disease. Documented successes of such therapies were the basis for this study. So far, there is no data related to the effectiveness of inulin application in symptomatic or severe pouchitis in humans or in animal model. The aim of the study was to determine the effect of inulin supplementation on the expression of intestinal inflammation and feeding efficiency in rats with induced pouchitis. Twenty-four Wistar rats were operated. After induction of pouchitis animals were randomly divided into control and supplementation groups receiving, respectively, semi-synthetic diet with or without inulin (in a lower (LD) or higher (HD) dose: 2.5 % or 5 % of total dietary content of mass) for a period of 6 weeks. Selected nutritional parameters were assessed throughout the study. Histopathological and immunohistochemical analysis of pouch mucosa specimens was also performed. The energy intake, weight gain, feeding efficiency, quality of stools were comparable in all studied groups. The intensity of inflammation (Moskovitz scale) and adaptive changes (Laumonier scale) did not differ between compared groups. The tissue expression of pro- and anti-inflammatory interleukins (IL-1α, IL-6, IL-10 and IL-12) was not different either. Inulin supplementation does not improve the quality of stools or the expression of intestinal inflammation in rats with induced pouchitis. It has no impact on the intensity of pouch adaptation or on feeding efficiency.