Role Of Changes In Expression Research Articles

Development of prednisone resistance in naïve canine lymphoma: Longitudinal evaluation of NR3C1α, ABCB1, and 11β-HSD mRNA expression.

Prednisone resistance develops rapidly and essentially universally when dogs with lymphoma are treated with corticosteroids. We investigated naturally occurring mechanisms of prednisone resistance in seven dogs with naïve multicentric lymphoma, treated with oral prednisone; four dogs were administered concurrent cytotoxic chemotherapy. Expression of NR3C1α, ABCB1 (formerly MDR1), 11β-HSD1, and 11β-HSD2 mRNA was evaluated in neoplastic lymph nodes by real-time RT-PCR. Changes of expression levels at diagnosis and at time of clinical resistance to prednisone were compared longitudinally using a Wilcoxon signed-rank test. Clinical resistance to prednisone was observed after a median of 68days (range: 7-348days) after initiation of treatment. Relative to pretreatment samples, prednisone resistance was associated with decreased NR3C1α expression in biopsies of all dogs with high-grade lymphoma (six dogs, p=.031); one dog with indolent T-zone lymphoma had increased expression of NR3C1α. Resistance was not consistently associated with changes in ABCB1, 11β-HSD1, or 11β-HSD2 expression. Decreased expression of the glucocorticoid receptor (NR3C1α) may play a role in conferring resistance to prednisone in dogs with lymphoma. Results do not indicate a broad role for changes in expression of ABCB1, 11β-HSD1, and 11β-HSD2 in the emergence of prednisone resistance in lymphoma-bearing dogs.

Effect of alterations in apoptotic pathway on development of metabolic syndrome in patients with psoriasis vulgaris.

An increase in the incidence of metabolic syndrome (MetS) has been identified in patients with psoriasis. To evaluate the role of changes in expression of apoptosis activators [B-cell lymphoma (Bcl)-2-like protein 4 (BAX), cytochrome c (cytC) and caspase-3 (CASP3)] and apoptosis inhibitors [Bcl-2, survivin, cyclin D1 (CCND1), superoxide dismutase (SOD), catalase 3 (CAT), glutathione synthetase (GS), heat shock protein (Hsp)27, Hsp60, Hsp70 and Hsp90] on development of MetS in patients with psoriasis vulgaris. Fifty patients with psoriasis were enrolled; 25 had MetS. Twenty-five healthy people and 25 people with only MetS were included as a control group. Serum fasting blood glucose, urea, creatinine, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, thyroid-stimulating hormone, fraction of thyroxine, fasting insulin and highly sensitive C-reactive protein levels were measured. Expression of BAX, cytC, CASP3, Bcl-2, survivin, CCND1, SOD, CAT, GS, and Hsp27, Hsp60, Hsp70 and Hsp90 were measured in peripheral blood. Clinical activation of patients with psoriasis was calculated using Psoriasis Area and Severity Index scores. In patients with MetS there was an increase in expression of genes for cytC, survivin and Hsp27, Hsp60 and Hsp90, and a decrease in expression of CCND1. Furthermore, expression levels of CCND1 were identified to be an independent risk factor for MetS development in patients with psoriasis. The increase in expression of survivin and Hsp27, Hsp60 and Hsp90, and the decrease in CCND1 expression may be important mechanisms in the development of MetS in patients with psoriasis.

Gene-Expression Changes Caused by Inbreeding Protect Against Inbreeding Depression in Drosophila

We present a transcriptomic analysis aimed at investigating whether the changes in gene expression that occur under inbreeding generally reduce or enhance inbreeding depression. Discerning between these two alternatives can be addressed only when both changes in expression due to inbreeding and to inbreeding depression are estimated simultaneously. We used Affymetrix 2.0 arrays to study the changes in gene expression associated with both inbreeding and inbreeding depression for fitness in four sets of inbred sublines of Drosophila melanogaster. We found that for most genes showing changes in expression associated with inbreeding, the least depressed sublines were those showing the largest departures in expression from that of the outbred control. This suggests a pattern consistent with a protective role of expression changes against inbreeding effects, and would reveal a new dimension of the transcriptomics of inbreeding. The variation in depression observed could then be due not only to the genetic damages primarily originating that depression, but also possibly to differences in the ability to carry out the appropriate adjustments in gene expression to cope with the inbreeding. We also found that these expression changes with a putative protective role against inbreeding effects show a clear specificity on RNA synthesis and splicing and energy derivation functions.

Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats

Aim of the study We investigated the preventive effect of Momordica charantia Linn. (Cucurbitaceae) fruit, commonly known as bitter melon, on hyperglycemia and insulin resistance in rats fed with a fructose-enriched diet. Materials and methods First, rats were divided randomly into two groups: the control group was fed with control diet, whereas the experimental group was fed with a 60% high-fructose diet for 8 weeks. After the first 6 weeks, the fructose-treated rats were further subdivided into six groups and were orally fed with or without Momordica charantia L. or rosiglitazone (ROS) for 2 weeks while rats were still on fructose diet. Results We demonstrated that bitter melon was effective in ameliorating the fructose diet-induced hyperglycemia, hyperleptinemia, hyperinsulinemia, and hypertriglyceridemia as well as in decreasing the levels of free fatty acid (FFA) ( P < 0.001, P < 0.05, P < 0.05, P < 0.05, P < 0.05, respectively). Bitter melon reversed fructose diet-induced hypoadiponectinemia ( P < 0.05), which provides a therapeutic advantage to insulin resistance in improving insulin sensitivity. Additionally, bitter melon decreased the weights of epididymal ( P < 0.05) and retroperitoneal white adipose tissue (WAT) ( P < 0.05). Bitter melon increased the expression of peroxisome proliferator-activated receptor γ (PPARγ) in white adipose tissue (WAT). Conversely, bitter melon decreased the expression of leptin in WAT. Furthermore, we demonstrate that bitter melon significantly increases the mRNA expression and protein of glucose transporter 4 (GLUT4) in skeletal muscle. Conclusions This study demonstrates, for the first time, the beneficial effects of two different extracts of bitter melon on insulin resistance in rats fed a high-fructose diet thereby producing evidence of the role of changes in expression of PPARγ and GLUT4.