Regulatory feedback loop between T3 and microRNAs in renal cancer.

microRNAs, short non-coding RNAs, influence key physiological processes, including hormonal regulation, by affecting the expression of genes. In this study we hypothesised that the expression of microRNAs targeting thyroid hormone pathway genes may be in turn regulated by thyroid hormone signalling. It is known that the expression of DIO1, a gene contributing to triiodothyronine (T3) signalling, is regulated by miR-224. Thus, we analysed mutual regulation between triiodothyronine pathway and miR-224/miR-452/GABRE cluster. Firstly, we found that miR-452 directly regulates the expression of thyroid hormone receptor TRß1 in renal cancer cells. In turn, the expression of miR-224/452/GABRE cluster and other microRNAs targeting TRß1 was influenced by T3 treatment and/or TR silencing. miR-452 expression correlated with intracellular T3 concentrations in renal tumours. In conclusion, we propose a new mechanism of feedback regulation, by which in renal cancer microRNAs regulate the expression of T3 pathway genes, while T3 in turn regulates expression of microRNAs.

In the era of the universal use of statins dyslipidemia's are still common in heart transplant recipients: a cross-sectional study.

BACKGROUND: Statins are used in orthotopic heart transplant (OHT) recipients to avoid acute rejection episodes (ARE) during the first year after surgery and coronary vasculopathy (CAV) thereafter as established in prospective randomized trials, yielding the grounds for the universal use of this group of drugs. The aim of the study was to describe the occurrence of dyslipidemias among OHT recipients after introduction of guidelines suggesting the use of statins in all individuals able to tolerate this therapy. METHODS: Medical records of all OHT recipients undergoing routine clinical checkups between January and June 2010 were screened for the presence of dyslipidemia: total cholesterol>5 mmol/L; low-density lipoprotein (LDL)-cholesterol>3 mmol/L; triglycerides>1.65 mmol/L; high-density lipoprotein (HDL)<1 mmol/L in the serum. The study group consisted of 322 subjects including 265 males and 57 females of overall mean age of 53.6±12 and 7±4 years after OHT. There was coronary artery disease (CAD) before OHT in 113 (35%). The average number of ARE was 1.9±1.9 and CAV was diagnosed in 77 (24%) patients. There were 247 (77%) patients on statins. We analyzed clinical, ultrasound, and biochemical evaluations to characterize subjects with dyslipidemias. RESULTS: At least one dyslipidemia was observed among 212 (66%) including hypercholesterolemia in 121 (38%), high LDL in 135 (42%), hypertriglyceridemia in 110 (34%), and low HDL in 48 (15%) patients. The subjects with dyslipidemia were prone to be older, to have CAD before OHT, and to be hypertensive, overweight, and obese, as well as display an higher HbA1C when diabetic. They were treated less frequently with tacrolimus but showed higher drug levels, and more often were prescribed everolimus. CONCLUSIONS: Despite almost universal use of statins, dyslipidemias were present in 2/3 of OHT recipients. It was related to typical atherosclerotic risk factors; however, the influence of immunosuppressants seemed to also be significant.

Cell-mediated immune reactions in measles.

Cell-mediated reactions in measles cases, in direct contacts and healthy children were tested. Indices of phytohaemagglutinin-stimulated blastic transformation and leukocyte migration inhibition were evaluated. Positive reactions were found in the first and second weeks after manifestation of clinical symptoms. The application of glucocorticosteroids in clinical complications resulted in delayed and reduced leukocyte migration inhibition. Studies on seronegative contacts suggested that positive cell-mediated reactions may appear before manifestation of clinical symptoms.