Biochemical and cellular consequences of lumiflavin-induced riboflavin depletion in human epithelial cells

Riboflavin is an essential component of the human diet, with an established role for its derivative cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), in oxidative metabolism. It has previously been demonstrated that luminal but not systemic riboflavin depletion leads to a dysregulation of normal gastrointestinal development. It is hypothesised that riboflavin depletion of intestinal cells in culture interrupts cell signalling pathways, with associated adverse functional effects. The overall aim was to develop and characterise an intestinal cell model of riboflavin depletion using the structural analogue of riboflavin, lumiflavin, which inhibits riboflavin uptake, and to assess the role of riboflavin on cell signalling. A model of riboflavin depletion was established in three intestinal cell lines, (Caco-2, HCT116 and HT29) through treatment with lumiflavin. Intracellular flavin concentrations and glutathione reductase activation coefficient (GRAC) were measured as markers of riboflavin status. Intracellular ATP concentration, the generation of reactive oxygen species (ROS), clonogenicity and apoptotic DNA fragmentation were determined. Effects of riboflavin depletion on cell signalling were examined in only Caco-2 cells. Changes in the phosphorylation of amino acid residues were determined as an indicator of effects on cell signalling, using western blot and high content analysis (HCA). Isobaric tagging for relative and absolute quantitation (iTRAQ) was used for phosphoprotein profiling, followed by validation of the findings by western blot. HCA and flow cytometry were used to determine changes in the cell cycle. Cell growth was inhibited by lumiflavin in all three cell lines, in a concentration-dependent manner. Intracellular flavin status was significantly decreased in all cell lines by 48 hours. Riboflavin depletion by lumiflavin led to a significant reduction in intracellular ATP concentration and an enhanced generation of ROS in all cell lines. A cell-specific irreversible loss of proliferative ability was observed. The effect of riboflavin depletion on oxidative stress and disruption of energy generation may have contributed to the observed effects on cell proliferation. There was no effect of lumiflavin on apoptotic DNA fragmentation in any cell line. Lumiflavin resulted in changes in the global phosphorylation of tyrosine by 3-6 hours, before biochemical riboflavin depletion was evident. Significant changes in mRNA processing and apoptosis pathways were found. Lumiflavin seemed to suppress cell signalling. Lumiflavin also caused arrest of cells in S phase with a subsequent G2/M phase block. In conclusion, riboflavin depletion of intestinal cells by lumiflavin had biochemical and functional consequences. Alterations in cell signalling and arrest in S phase with induction of apoptosis in response to lumiflavin may be causative of adverse consequences on intestinal cell proliferation

Tai Chi for Lower Urinary Tract Symptoms and Quality of Life in Elderly Patients with Benign Prostate Hypertrophy: A Randomized Controlled Trial

Tai chi exercise has been recommended as suitable for the improvement of health in the elderly. The purpose of this study was to investigate the effects of tai chi on lower urinary tract symptoms (LUTSs), quality of life (QoL), and sex hormone levels in patients with benign prostate hypertrophy (BPH). The elderly patients with BPH were randomized to receive tai chi or usual care. Fifty-six participants were randomized into either the tai chi group (n = 28) or the control group (n = 28). After 12 weeks of treatment, the tai chi group showed significant improvement in LUTS and QoL. There was a significant effect of tai chi on testosterone but no significant effect on insulin or glucose. No serious adverse events were observed during the study period. In conclusion, our results suggest that 12 weeks of tai chi may improve LUTS and QoL in elderly patients with BPH

Importance of lactic acid bacteria in Asian fermented foods

Lactic acid bacteria play important roles in various fermented foods in Asia. Besides being the main component in kimchi and other fermented foods, they are used to preserve edible food materials through fermentation of other raw-materials such as rice wine/beer, rice cakes, and fish by producing organic acids to control putrefactive microorganisms and pathogens. These bacteria also provide a selective environment favoring fermentative microorganisms and produce desirable flavors in various fermented foods. This paper discusses the role of lactic acid bacteria in various non-dairy fermented food products in Asia and their nutritional and physiological functions in the Asian diet

Autonomous control of terminal erythropoiesis via physical interactions among erythroid cells

AbstractIn vitro erythropoiesis has been studied extensively for its application in the manufacture of transfusable erythrocytes. Unfortunately, culture conditions have not been as effective as in vivo growth conditions, where bone marrow macrophages are known to be a key regulator of erythropoiesis. This study focused on the fact that some erythroblasts are detached from macrophages and only contact other erythroblasts. We hypothesized that additional factors regulate erythroblasts, likely through either physical contact or secreted factors. To further elucidate these critical factors, human erythroblasts derived from cord blood were cultured at high density to mimic marrow conditions. This growth condition resulted in a significantly increased erythroid enucleation rate and viability. We found several novel contact-related signals in erythroblasts: intercellular adhesion molecule-4 (ICAM-4) and deleted in liver cancer-1 (DLC-1). DLC-1, a Rho-GTPase-activating protein, has not previously been reported in erythroid cells, but its interaction with ICAM-4 was demonstrated here. We further confirmed the presence of a secreted form of human ICAM-4 for the first time. When soluble ICAM-4 was added to media, cell viability and enucleation increased with decreased nuclear dysplasia, suggesting that ICAM-4 is a key factor in contact between cells. These results highlight potential new mechanisms for autonomous control of erythropoiesis. The application of these procedures to erythrocyte manufacturing could enhance in vitro erythrocyte production for clinical use

Toxic epidermal necrolysis induced by lamotrigine treatment in a child

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children

The Dendritic magnetic avalanches in carbon-free MgB2_2 thin films with and without a deposited Au layer

From the magneto optics images (MOI), the dendritic magnetic avalanche is known to appear dominantly for thin films of the newly discovered MgB$_2$. To clarify the origin of this phenomenon, we studied in detail the MOI of carbon-free MgB$_2$ thin films with and without a deposited gold layer. The MOI indicated carbon contamination was not the main source of the avalanche. The MOI clearly showed that the deposition of metallic gold deposition on top of a MgB$_2$ thin film improved its thermal stability and suppressed the sudden appearance of the dendritic flux avalanche. This is consistent with the previous observation of flux noise in the magnetization.Comment: 9 pages, 4 figeure

Radiomics and imaging genomics in precision medicine

“Radiomics,” a field of study in which high-throughput data is extracted and large amounts of advanced quantitative imaging features are analyzed from medical images, and “imaging genomics,” the field of study of high-throughput methods of associating imaging features with genomic data, has gathered academic interest. However, a radiomics and imaging genomics approach in the oncology world is still in its very early stages and many problems remain to be solved. In this review, we will look through the steps of radiomics and imaging genomics in oncology, specifically addressing potential applications in each organ and focusing on technical issues