Effects of genistein on insulin pathway-related genes in mouse differentiated myoblast C2C12 cell line: evidence for two independent modes of action

Introduction. Genistein (plant isoflavone) is a well-known anti-cancer drug with estrogenic-like properties. Genistein also regulates sugar and lipid metabolism; thus, it has anti-diabetic properties. The aim of the study was to evaluate in vitro effects of genistein on glucose transport, fatty acids oxidation, activation of PKB, and expression of genes related to insulin pathway in differentiated myoblast C2C12 mouse cell line. Material and methods. Differentiated myoblast C2C12 mouse cell line was used to assess the effects of different genistein concentrations on glucose transport and fatty acids oxidation measured by radioactivity technique, activation of PKB, and expression of selected genes related to insulin signaling pathway (IR-a, IR-b, IRS-1, PKB, GLUT-4, PP2A, SH-PTP2) at the mRNA and protein levels. Cells were incubated with various concentrations of genistein under standard conditions for 0–48 hours.Results. Genistein in low concentrations (0.1–1 μM) significantly increased glucose transport and decreased fatty acids oxidation in C2C12 cells after 48 h of incubation. High concentration of genistein (50 μM) had the opposite effect. Genistein stimulated PKB phosphorylation during the first 5–10 minutes of incubation. There was no significant impact on the protein expression of selected genes (IR-a, IR-b, IRS-1, PKB, GLUT-4, PP2A-Ca, ER-a and ER-b) after 48 h treatment. We observed inverse correlation between genistein concentration and the expression of SH-PTP2 protein. Genistein affected the expression pattern of mRNAs for genes related to the insulin pathway, however, not the expression of the encoded proteins. Conclusions. The results of this study showed that depending on the concentration and time of incubation genistein significantly affects glucose and lipid metabolism and at low concentration modifies expression patternof a few genes in C2C12 cells

Samotność idei? : społeczeństwo obywatelskie we współczesnym świecie

Publikacja recenzowana / Peer-reviewed publicationCelem niniejszej pracy jest próba przedstawienia kształtu obecnych relacji i stosunków między społeczeństwem obywatelskim a wspomnianymi ideami czy procesami społecznymi.Książka, którą oddajemy do rąk Czytelników jest zbiorem prac studialnych o zróżnicowanym poziomie analizy. Dla części autorów jest to próba pierwszej, samodzielnej pracy naukowo-badawczej, dla innych - kolejna okazja do podzielenia się przemyśleniami, ugruntowanymi wieloletnim doświadczeniem badawczym i studiami.Wszystkich połączyło i skłoniło do współpracy zainteresowanie tym samym - losem społeczeństwa obywatelskiego w zderzeniu z problemami współczesności

Cross-cultural adaptation and validation of the Polish version of the core outcome measures index for low back pain

PURPOSE: The Core Outcome Measures Index (COMI) is a short, multidimensional outcome scale validated for the use by patients with spinal disorders. It is a recommended instrument in the Spine Society of Europe Spine Tango Registry. The purpose of this study was to produce a cross-culturally adapted and validated Polish COMI. METHODS: The cross-cultural adaptation was carried out using the established guidelines. One-hundred and sixty-nine patients with chronic low back pain were enrolled, 89 took part in the reproducibility part of the study. Data quality, construct validity and reproducibility were assessed. RESULTS: The quality of data was very good with very few missing answers and modest floor effect. Reliability expressed as intraclass correlation coefficient (ICC) was 0.90 (95 % CI 0.85–0.93) for the overall COMI score and for most of the individual core items. The minimum detectable change (MDC(95%)) was 1.79. CONCLUSIONS: The Polish version of COMI showed a favorable reproducibility similar to that of previously tested language versions. The COMI scores correlated sufficiently with existing measures. This version of the COMI is a valuable instrument for the use by Polish-speaking patients with spinal disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00586-012-2607-2) contains supplementary material, which is available to authorized users

Fractalkine, sICAM-1 and Kynurenine Pathway in Restrictive Anorexia Nervosa–Exploratory Study

The link between the kynurenine pathway and immunomodulatory molecules—fractalkine and soluble intercellular adhesion molecule-1 (sICAM-1)—in anorexia nervosa (AN) remains unknown. Fractalkine, sICAM-1, tryptophan (TRP), kynurenine (KYN), neuroprotective kynurenic acid (KYNA), neurotoxic 3-OH-kynurenine (3-OH-KYN), and the expression of mRNA for kynurenine aminotransferases (KAT1-3) were studied in 20 female patients with restrictive AN (mostly drug-free, all during first episode of the disease) and in 24 controls. In AN, serum fractalkine, but not sICAM-1, KYNA, KYN, TRP or 3-OH-KYN, was higher; ratios TRP/KYN, KYN/KYNA, KYN/3-OH-KYN and KYNA/3-OH-KYN were unaltered. The expression of the gene encoding KAT3, but not of genes encoding KAT1 and KAT2 (measured in blood mononuclear cells), was higher in patients with AN. In AN, fractalkine positively correlated with TRP, while sICAM-1 was negatively associated with 3-OH-KYN and positively linked with the ratio KYN/3-OH-KYN. Furthermore, TRP and fractalkine were negatively associated with the body mass index (BMI) in AN. Expression of KAT1, KAT2 and KAT3 did not correlate with fractalkine, sICAM-1 or BMI, either in AN or control. Increased fractalkine may be an independent factor associated with the restrictive type of AN. Excessive physical activity probably underlies increased expression of KAT3 observed among enrolled patients. Further, longitudinal studies on a larger cohort of patients should be aimed to clarify the contribution of fractalkine and KAT3 to the pathogenesis of AN

Protocol for a multicenter, double-blind, randomized, placebo-controlled phase III trial of the inhaled Β2-adrenergic receptor agonist salbutamol for transient tachypnea of the newborn (the REFSAL trial)

BACKGROUND: Transient tachypnea of the newborn (TTN), which results from inadequate absorption of fetal lung fluid, is the most common cause of neonatal respiratory distress. Stimulation of β-adrenergic receptors enhances alveolar fluid absorption. Therefore, the β2-adrenergic receptor agonist salbutamol has been proposed as a treatment for TTN. This study aims to evaluate the efficacy and safety of salbutamol as supportive pharmacotherapy together with non-invasive nasal continuous positive airway pressure (NIV/nCPAP) for the prevention of persistent pulmonary hypertension of the newborn (PPHN) in infants with TTN. METHODS AND ANALYSIS: This multicenter, double-blind, phase III trial will include infants with a gestational age between 32 and 42 weeks who are affected by respiratory disorders and treated in eight neonatal intensive care units in Poland. A total of 608 infants within 24 h after birth will be enrolled and randomly assigned (1:1) to receive nebulized salbutamol with NIV or placebo (nebulized 0.9% NaCl) with NIV. The primary outcome is the percentage of infants with TTN who develop PPHN. The secondary outcomes are the severity of respiratory distress (assessed with the modified TTN Silverman score), frequency of need for intubation, duration of NIV and hospitalization, acid–base balance (blood pH, partial pressure of O(2) and CO(2), and base excess), and blood serum ionogram for Na(+), K(+), and Ca(2+). DISCUSSION: The Respiratory Failure with Salbutamol (REFSAL) study will be the first clinical trial to evaluate the efficacy and safety of salbutamol in the prevention of persistent pulmonary hypertension in newborns with tachypnea, and will improve short term outcomes. If successful, the study will demonstrate the feasibility of early intervention with NIV/nCPAP together with nebulized salbutamol in the management of TTN. ETHICS AND DISSEMINATION: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland on November 16, 2020 (decision number KB/190/2020). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. CLINICAL TRIAL REGISTRATION: It is registered at ClinicalTrials.gov NCT05527704, EudraCT 2020-003913-36; Protocol version 5.0 from 04/01/2022

External validation of the Ruptured Arteriovenous Malformation Grading Scale (RAGS) in a multicenter adult cohort

While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales

Cross-cultural adaptation and validation of the Polish version of the Core Outcome Measures Index for low back pain

PURPOSE: The Core Outcome Measures Index (COMI) is a short, multidimensional outcome scale validated for the use by patients with spinal disorders. It is a recommended instrument in the Spine Society of Europe Spine Tango Registry. The purpose of this study was to produce a cross-culturally adapted and validated Polish COMI. METHODS: The cross-cultural adaptation was carried out using the established guidelines. One-hundred and sixty-nine patients with chronic low back pain were enrolled, 89 took part in the reproducibility part of the study. Data quality, construct validity and reproducibility were assessed. RESULTS: The quality of data was very good with very few missing answers and modest floor effect. Reliability expressed as intraclass correlation coefficient (ICC) was 0.90 (95 % CI 0.85–0.93) for the overall COMI score and for most of the individual core items. The minimum detectable change (MDC(95%)) was 1.79. CONCLUSIONS: The Polish version of COMI showed a favorable reproducibility similar to that of previously tested language versions. The COMI scores correlated sufficiently with existing measures. This version of the COMI is a valuable instrument for the use by Polish-speaking patients with spinal disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00586-012-2607-2) contains supplementary material, which is available to authorized users