The role of octamer binding transcription factors in glioblastoma multiforme.

A group of transcription factors (TF) that are master developmental regulators of the establishment and maintenance of pluripotency during embryogenesis play additional roles to control tissue homeostasis and regeneration in adults. Among these TFs, members of the octamer-binding transcription factor (OCT) gene family are well documented as major regulators controlling the self-renewal and pluripotency of stem cells isolated from different adult organs including the brain. In the last few years a large number of studies show the aberrant expression and dysfunction of OCT in different types of cancers including glioblastoma multiforme (GBM). GBM is the most common malignant primary brain tumor, and contains a subpopulation of undifferentiated stem cells (GSCs), with self-renewal and tumorigenic potential that contribute to tumor initiation, invasion, recurrence, and therapeutic resistance. In this review, we have summarized the current knowledge about OCT family in GBM and their crucial role in the initiation, maintenance and drug resistance properties of GSCs. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin.

The effect of a 10-week Nordic walking training program on the level of GH and LH in elderly women.

OBJECTIVE: The aim of this study was to determine the effect of a 10-week Nordic walking training program on resting growth hormone (GH) and luteinizing hormone (LH) blood concentrations and their relationships to the values of inflammatory, metabolic, and muscle injury parameters in postmenopausal women with overweight and obesity. METHODS: Thirty-two postmenopausal women with overweight or obesity (body mass index 30.5 ± 4.1 kg/m(2)), aged 59.6 ± 5.9 years were included in the investigation. Concentrations of GH, LH, C-reactive protein, total cholesterol, low density (LDL) and high density lipoprotein (HDL) cholesterol, triglycerides and albumin, as well as the plasma activity of muscle enzymes such as creatine kinase and lactate dehydrogenase, were examined before and after the participants finished a 10-week Nordic walking rehabilitation program. RESULTS: After a 10-week rehabilitation period in accordance with a Nordic walking program, significant increases in blood concentrations of GH (median 47.5%) and HDL cholesterol (on average by 0.1%) as well as a decrease in LH values (on average by 19%), total cholesterol, LDL cholesterol and triglycerides (all on a similar average by between 0.1 and 0.2%), creatine kinase (on average by 14%), lactate dehydrogenase (on average by 4%), C-reactive protein (on average by 24%), and body mass index (on average by 5.7%) were found. CONCLUSIONS: Nordic walking for postmenopausal women with overweight and obesity led to favorable hormonal responses, as well as improvement in muscle integrity and nutritional and inflammatory states, suggesting chronic, regular exercise as an effective tool in protecting against menopause-related catabolic processes.

Stress hyperglycaemia in patients with first myocardial infarction.

OBJECTIVE: To investigate the incidence of stress hyperglycaemia at first acute myocardial infarction (MI) with ST-segment elevation, occurrence of stress hyperglycaemia as a manifestation of previously undiagnosed abnormal glucose tolerance (AGT), and its relation to stress hormone levels. MATERIALS AND METHODS: The population of this prospective cohort study consisted of 243 patients. On admission glucose, adrenaline, noradrenaline and cortisol levels were measured. Patients without previously diagnosed diabetes (n = 204) underwent an oral glucose tolerance test on day 3 of hospitalisation and 3 months after discharge. RESULTS: Abnormal glucose tolerance at day 3 was observed in 92 (45.1%) patients without a previous diagnosis of diabetes mellitus and resolved after 3 months in 46 (50.0%) patients (p < 0.0001). Stress hyperglycaemia, defined as admission glycaemia ≥ 11.1 mmol/l, affected 34 (14.0%) study participants: 28 (54.9%) patients with diabetes vs. 3 (8.8%) subjects with newly detected impaired glucose intolerance (p < 0.00001) and 1 (2.2%) person with AGT at day 3 (p < 0.000001). Multivariable analysis identified elevated glycated haemoglobin (HbA(1c) ; p < 0.0000001), anterior MI (p < 0.05) and high admission cortisol concentration (p < 0.001), but not catecholamines, as independent predictors of stress hyperglycaemia. The receiver operating characteristic curve analysis revealed the optimal cut-off values of 8.2% for HbA(1c) and 47.7 µg/dl for admission cortisol with very good and sufficient diagnostic accuracies respectively. CONCLUSIONS: Newly detected AGT in patients with a first MI is transient in 50% of cases. Stress hyperglycaemia is a common finding in patients with a first MI with ST-segment elevation and diabetes mellitus, but is rarely observed in individuals with impaired glucose tolerance or transient AGT diagnosed during the acute phase of MI. The risk factors of stress hyperglycaemia occurrence include elevated HbA(1c) , anterior MI and high admission cortisol concentration.

The nuclear DICER-circular RNA complex drives the deregulation of the glioblastoma cell microRNAome.

The assortment of cellular microRNAs ("microRNAome") is a vital readout of cellular homeostasis, but the mechanisms that regulate the microRNAome are poorly understood. The microRNAome of glioblastoma is substantially down-regulated in comparison to the normal brain. Here, we find malfunction of the posttranscriptional maturation of the glioblastoma microRNAome and link it to aberrant nuclear localization of DICER, the major enzymatic complex responsible for microRNA maturation. Analysis of DICER's nuclear interactome reveals the presence of an RNA binding protein, RBM3, and of a circular RNA, circ2082, within the complex. Targeting of this complex by knockdown of circ2082 results in the restoration of cytosolic localization of DICER and widespread derepression of the microRNAome, leading to transcriptome-wide rearrangements that mitigate the tumorigenicity of glioblastoma cells in vitro and in vivo with correlation to favorable outcomes in patients with glioblastoma. These findings uncover the mechanistic foundation of microRNAome deregulation in malignant cells.

[A model for medical care of gestational diabetes]. / Model opieki nad ciezarna chora na cukrzyçe.

Our approach to taking care of 122 diabetic pregnant women was presented. At first, they were hospitalized in the Pathological Pregnancy Ward. An intensive insulin therapy (human insulin) was initiated and all the patients were educated. The pregnant appeared as an outpatient every fortnight within the first part of pregnancy and every seven to ten days in the second one. They were hospitalized for a few days in 12th and 24th week of pregnancy and from 36th/37th week until delivery. Unfortunately, their first arrival to our center was too late, usually with diabetes out of control. There were 3 miscarriages (2.4%), 111 newborns were in a satisfactory condition (91%), 4 died (3.3%), congenital malformations were found in four others (3.3%). A successful course of pregnancy was dependent upon a proper care taken of patients early enough, good cooperation with them and related with it satisfactory metabolic control of diabetes.

[Von Willebrand factor in hemodialysed patients with chronic renal failure]. / Czynnik von Willebranda u chorych hemodializowanych z powodu przewleklej niewydolnosci nerek.

The aim of the work was to evaluate the von Willebrand factor antigen (vWF Ag) concentration in the blood plasma of hemodialysed patients with chronic renal failure. The study was performed in the group of 43 patients (means aged 42.8 years) with chronic renal failure dialysed means 4 hours 3 times a week. The blood was obtained before and after hemodialyze and in 11 patients additionally after 1 year of systematic hemodialyze. The control group consisted of 51 healthy volunteers means aged 35.6 years. In the citric blood plasma concentration of vWF Ag was determined using immunosorbed enzyme-linked assay (ELISA). In the blood plasma of patients with chronic renal failure significantly higher concentration of vWF Ag than in controls was observed. 4-hours and 1-year dialyze did not influence the level of vWF Ag in patients with chronic renal failure.

Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320.

PTEN (Phosphatase and tensin homolog deleted on chromosome 10) expression in stromal fibroblasts suppresses epithelial mammary tumours, but the underlying molecular mechanisms remain unknown. Using proteomic and expression profiling, we show that Pten loss from mammary stromal fibroblasts activates an oncogenic secretome that orchestrates the transcriptional reprogramming of other cell types in the microenvironment. Downregulation of miR-320 and upregulation of one of its direct targets, ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2) are critical events in Pten-deleted stromal fibroblasts responsible for inducing this oncogenic secretome, which in turn promotes tumour angiogenesis and tumour-cell invasion. Expression of the Pten-miR-320-Ets2-regulated secretome distinguished human normal breast stroma from tumour stroma and robustly correlated with recurrence in breast cancer patients. This work reveals miR-320 as a critical component of the Pten tumour-suppressor axis that acts in stromal fibroblasts to reprogramme the tumour microenvironment and curtail tumour progression.