Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)

Influence of hyperinsulinemic – hypoglycemic clamp on induced platelet aggregation, activity of physiological anticoagulants and von Willebrand factor in patients with type I diabetes

Background. Intensive glycaemic control in patients with type 1 diabetes may lead to hypoglycaemia and thus increase the risk of cardiovascular and cerebrovascular events. Platelet activation and/or decreased activity of physiological anticoagulants during hypoglycaemia may play a role in the development of cardiovascular or cerebrovascular complications. Aims. To investigate induced platelet activity, the activity of physiological anticoagulants, and the von Wil-lebrand factor in patients with type 1 diabetes with the hyperinsulinaemichypoglycaemic clamp. Materials and methods. We examined 11 patients with type 1 diabetes without macro- and micro-vascular complications (6 males, 5 females, mean age 23.7 5.6 years, A1C 9.7 2.3%). Induced platelet aggregation, physiological anticoagulants (Protein S, Protein C, AT III) and the von Willebrand factor were studied at hyperglycaemic, euglycaemic, and hypoglycaemic stages during use of a hyperinsulinaemic (1 mU/kg/min) hypoglycaemic clamp. Results. Platelet aggregation to all agonists increased significantly during the hypoglycaemic stage, compared with the euglycaemic or hyperglycaemic stages. There was no difference in platelet aggregation between the euglycaemic and hyperglycaemic stages. Platelet aggregation to all agonists increased during the hypoglycaemic stage compared with the hyperglycaemic period: thrombin23.9%, ADP30.6%, arachidonic acid30.9%, collagen69.4% and ristocetin70.8%. During hypoglycaemia aggregation to ADP, arachidonic acid and collagen remained within normal limits (upper quartile); aggregation to thrombin was significantly above normal limits and aggregation to ristocetin remained significantly below lower limits. Protein S activity was significantly increased during hypoglycaemia compared with euglycaemia (p = 0.046) and hyperglycaemia (p = 0.046). Antithrombin-III activity decreased significantly at the euglycaemic and hypoglycaemic stages, compared with the hyperglycaemic period, but still remained significantly elevated above the upper threshold. Protein C and vWf activity did not change significantly. Conclusions. In patients with type 1 diabetes platelet aggregation and protein S activity increases significantly at the hypoglycaemic stage of the hyperinsulinaemichypoglycaemic clamp. Platelet activation is directly caused by hypoglycaemia and not by decreasing glucose levels. Increased protein S activity is a compensatory response to platelet activation

I-MOVE multicentre case–control study 2010/11 to 2014/15 : is there within-season waning of influenza type/subtype vaccine effectiveness with increasing time since vaccination?

Influenza vaccines are currently the best method available to prevent seasonal influenza infection. In most European countries one dose (or two doses for children) of seasonal vaccine is given from September to December to the elderly and other target groups for vaccination. In Europe, influenza seasons can last until mid-May (1), and it is expected that vaccination conveys protection on the individual for the duration of the season. In 13/15 reviewed studies on the length of vaccine-induced protection among the elderly, using anti-haemagglutination antibody titres as a proxy for seroprotection levels, seroprotection rates lasted at least >4 months after vaccination (2). However in the 2011-12 influenza season various studies in Europe reported a decrease in influenza vaccine effectiveness (VE) against A(H3N2) over time within the season (3–5). In the United States, a decrease in VE against A(H3N2) with time since vaccination was suggested in the 2007-8 influenza season (6). The observed decrease of VE over time can be explained by viral change (notably antigenic drift) occurring in the season. Drift in B viruses may be slower than in A viruses (7), and A(H3N2) viruses undergo antigenic drift more frequently than A(H1N1)pdm09 viruses (8). The decrease of VE over time can also be explained by a waning of the immunity conferred by the vaccine independently from viral changes. If vaccine-induced protection wanes more rapidly during the season, then depending on the start and duration of the influenza season, the decline of VE may cause increases in overall incidence, hospitalisations and deaths. Changes to vaccination strategies (timing and boosters) may be needed. As anti-haemagglutination antibody titres are not well defined as a correlate of protection (9,10), vaccine efficacy (as measured in trials) or vaccine effectiveness observational studies may be one way to measure vaccine-induced protection. These studies require a large sample size to model VE by time since vaccination and currently, most of the seasonal observational studies lack the precision required to provide evidence for waning immunity. In this study we pooled data across five post-pandemic seasons (2010/11-2014/15) from the I-MOVE (Influenza - Monitoring Vaccine Effectiveness) multicentre case control studies (1,3,11,12), to obtain a greater sample size to study the effects of time since vaccination on influenza type/subtype-specific VE. We measure influenza type/subtype-specific VE by time since vaccination for the overall season, but also in the early influenza phase; under the hypothesis that virological changes are fewer in the early season, but waning of the vaccine effect should be present regardless of time within the influenza phase

Electrochemical degradation of Diclofenac on catalysts based on CNT and M/CNT modified electrodes

Diclofenac (DCF) - a nonsteroidal anti-inflammatory drug - is one of the most frequently detected pharmaceutical compounds in the aquatic environment. Because of its negative effects on public health and environment, this emerging pollutant monitoring and removal from wastewater are of high importance. Electrochemical oxidation has attracted growing interest in the last years, due to its versatility, high efficiency and environment compatibility.Electrochemical oxidation of DCF has been studied using multiwalled carbon nanotubes (CNT) and monometallic catalysts based on carbon nanotubes (M/CNT), at different pH media. The electroreactivity of DCF on modified electrodes and the kinetic parameters of the redox reactions were determined using cyclic voltammetry. Electrodegradation of DCF in aqueous medium was carried out using long-term electrolyses. The products of these electrolyses were identified and quantified by HPLC-MS, GC-MS, HPLC-UV-RID and IC.BioTecNorte (operation NORTE-01-0145-FEDER-000004) and “AIProcMat@N2020 -Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”, NORTE-01-0145-FEDER- 000006, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work also has been funded by national funds (FCT, Fundação para a Ciência e a Tecnologia), through the projects: PTDC/AAGTEC/5269/2014, Centre of Chemistry (UID/QUI/00686/2013 and UID/QUI/0686/2016) and LSRE-LCM (POCI-01-0145-FEDER-006984)info:eu-repo/semantics/publishedVersio

Neustonic versus epiphytic bacteria of eutrophic lake and their biodegradation ability on deltamethrin

This study evaluated biodegradation of the insecticide deltamethrin (1 μg l−1) by pure cultures of neustonic (n = 25) and epiphytic (n = 25) bacteria and by mixed cultures (n = 1), which consisted of a mixture of 25 bacterial strains isolated from the surface microlayer (SM ≈ 250 μm) and epidermis of the Common Reed (Phragmites australis, (Cav.) Trin. ex Steud.) growing in the littoral zone of eutrophic lake Chełmżyńskie. Results indicate that neustonic and epiphytic bacteria are characterized by a similar average capacity to degrade deltamethrin. After a 15-day incubation, bacteria isolated from the surface microlayer reduced the initial concentration of deltamethrin by 60%, while the average effectiveness of the bacteria found on the Common Reed equaled 47%

Regulation of Lipogenesis by Glucocorticoids and Insulin in Human Adipose Tissue

Patients with glucocorticoid (GC) excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc) and omental (om) adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM) of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes

Taxonomic distribution and origins of the extended LHC (light-harvesting complex) antenna protein superfamily

<p>Abstract</p> <p>Background</p> <p>The extended light-harvesting complex (LHC) protein superfamily is a centerpiece of eukaryotic photosynthesis, comprising the LHC family and several families involved in photoprotection, like the LHC-like and the photosystem II subunit S (PSBS). The evolution of this complex superfamily has long remained elusive, partially due to previously missing families.</p> <p>Results</p> <p>In this study we present a meticulous search for LHC-like sequences in public genome and expressed sequence tag databases covering twelve representative photosynthetic eukaryotes from the three primary lineages of plants (Plantae): glaucophytes, red algae and green plants (Viridiplantae). By introducing a coherent classification of the different protein families based on both, hidden Markov model analyses and structural predictions, numerous new LHC-like sequences were identified and several new families were described, including the red lineage chlorophyll <it>a/b</it>-binding-like protein (RedCAP) family from red algae and diatoms. The test of alternative topologies of sequences of the highly conserved chlorophyll-binding core structure of LHC and PSBS proteins significantly supports the independent origins of LHC and PSBS families via two unrelated internal gene duplication events. This result was confirmed by the application of cluster likelihood mapping.</p> <p>Conclusions</p> <p>The independent evolution of LHC and PSBS families is supported by strong phylogenetic evidence. In addition, a possible origin of LHC and PSBS families from different homologous members of the stress-enhanced protein subfamily, a diverse and anciently paralogous group of two-helix proteins, seems likely. The new hypothesis for the evolution of the extended LHC protein superfamily proposed here is in agreement with the character evolution analysis that incorporates the distribution of families and subfamilies across taxonomic lineages. Intriguingly, stress-enhanced proteins, which are universally found in the genomes of green plants, red algae, glaucophytes and in diatoms with complex plastids, could represent an important and previously missing link in the evolution of the extended LHC protein superfamily.</p