The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma

AbstractTo test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity

Hypoglycemic effects of vanadium on alloxan monohydrate induced diabetic dogs

The hypoglycemic effects after oral administration of vanadium have been studied previously in many species such as rats, mice and even humans. However, there has been no prior report on the glucose lowering effect of vanadium on diabetic dogs. Therefore, the purpose of this study was to evaluate the hypoglycemic effects of oral vanadium on diabetic dogs. Diabetes mellitus in the dogs studied was induced by alloxan monohydrate intravenous injection. The dogs were divided into two groups, one was the diabetic control (DC) group (n = 4) and the other was the vanadium treated (DV) group (n = 6). Fresh water was supplied to the dogs in the DC group, but sodium metavanadate solution (0.1~0.2 mg/ml) was given to the dogs in DV group from one week after the alloxan injection. The fasting glucose levels, fructosamine and serum chemistry profiles were compared between the two groups weekly for three weeks. The fasting blood glucose levels in DV group were significantly lower than those in the DC group (p < 0.01). Fructosamine levels in the DV group were also lower than those in the DC group (p < 0.05). The serum chemistry profiles were not significantly different in comparisons between the two groups. However, the cholesterol levels were significantly lower in the DV group compared to the DC group (p < 0.05). Our findings showed that oral vanadium administration had a hypoglycemic effect on chemically induced diabetic dogs

Occurrence of patulin in various fruit juices from South Korea: An exposure assessment

This research article published by Springer Nature Switzerland AG., 2010To determine patulin in various fruit juices, high performance liquid chromatography (HPLC) method was optimized and validated. For validation of HPLC method, a linearity, accuracy, precision, detection limit, and quantification limit were determined. Linearity (R2 = 0.99995), accuracy (96.1–115.7%), precision (3.31–9.52), detection limit (6 ng/mL), and quantification limit (8 ng/mL) were in agreement with performance criteria for patulin as set by the European Commission hence proved that HPLC can be used to detect patulin in fruit juices. After validation, the method was applied to estimate the prevalence of patulin in fruit juices (apple, grape, and orange juices). Nine samples (12.5%, 3 apple, 2 orange, and 4 grape juices) of 72 samples were positive for patulin in the range 2.8 to 30.9 ng/mL. According to the monitoring results, daily intake was estimated to be 0.17 ng/kg BW/day which was lower than the provisional maximum tolerable daily intake (0.4 μg/kg) established by Joint Expert Committee on Food Additives. These results indicate that the detection method coincides with the performance criteria and is appropriate for analysis of patulin, and continuous monitoring of patulin in various fruit juices from Korea is necessary

Generation and analysis of large-scale expressed sequence tags (ESTs) from a full-length enriched cDNA library of porcine backfat tissue

BACKGROUND: Genome research in farm animals will expand our basic knowledge of the genetic control of complex traits, and the results will be applied in the livestock industry to improve meat quality and productivity, as well as to reduce the incidence of disease. A combination of quantitative trait locus mapping and microarray analysis is a useful approach to reduce the overall effort needed to identify genes associated with quantitative traits of interest. RESULTS: We constructed a full-length enriched cDNA library from porcine backfat tissue. The estimated average size of the cDNA inserts was 1.7 kb, and the cDNA fullness ratio was 70%. In total, we deposited 16,110 high-quality sequences in the dbEST division of GenBank (accession numbers: DT319652-DT335761). For all the expressed sequence tags (ESTs), approximately 10.9 Mb of porcine sequence were generated with an average length of 674 bp per EST (range: 200–952 bp). Clustering and assembly of these ESTs resulted in a total of 5,008 unique sequences with 1,776 contigs (35.46%) and 3,232 singleton (65.54%) ESTs. From a total of 5,008 unique sequences, 3,154 (62.98%) were similar to other sequences, and 1,854 (37.02%) were identified as having no hit or low identity (<95%) and 60% coverage in The Institute for Genomic Research (TIGR) gene index of Sus scrofa. Gene ontology (GO) annotation of unique sequences showed that approximately 31.7, 32.3, and 30.8% were assigned molecular function, biological process, and cellular component GO terms, respectively. A total of 1,854 putative novel transcripts resulted after comparison and filtering with the TIGR SsGI; these included a large percentage of singletons (80.64%) and a small proportion of contigs (13.36%). CONCLUSION: The sequence data generated in this study will provide valuable information for studying expression profiles using EST-based microarrays and assist in the condensation of current pig TCs into clusters representing longer stretches of cDNA sequences. The isolation of genes expressed in backfat tissue is the first step toward a better understanding of backfat tissue on a genomic basis

Immunogenicity and Safety of Trivalent Inactivated Influenza Vaccine: A Randomized, Double-Blind, Multi-Center, Phase 3 Clinical Trial in a Vaccine-Limited Country

Influenza vaccines are the primary method for controlling influenza and its complications. This study was conducted as a phase 3, randomized, double-blind, controlled, multi-center trial at seven university hospitals to evaluate the immunogenicity and safety of an inactivated, split, trivalent influenza vaccine (GC501, Green Cross Corporation, Yongin, Korea), which was newly manufactured in Korea in 2008. Between September 21 and 26, a total of 329 healthy subjects were recruited for the immunogenicity analysis, while 976 subjects were enrolled for the safety analysis. The GC501 vaccine met both FDA and EMEA criteria with ≥ 80% of subjects achieving post-vaccination titers ≥ 40 for all three subtypes, even in the elderly. The vaccine was well tolerated with only mild systemic and local adverse events. In summary, GC501 showed excellent immunogenicity and a good safety profile in both young adults and the elderly. The licensure of GC501 might be an important basis in preparation for the future influenza pandemic

Characteristics of Nasal Resonance and Perceptual Rating in Prelingual Hearing Impaired Adults

ObjectivesResonance problems in hearing impaired (HI) individuals have been described as aspects of nasality. However, there are limitations in being able to explain the range of resonance problems. Therefore, this study suggests a perceptual rating that will effectively explain the characteristics of resonance problems in HI individuals.MethodsNasalance scores were obtained from 32 subjects in each of HI and normal hearing (NH) groups using a nasometer. The subjects were categorized into groups based on normal and abnormal nasalance ranges. The abnormal nasalance range group was further divided into hyper-, hypo-, and mixed-nasal groups. Nasalance scores were based the individuals performance in a series of passage and syllable tasks. The perceptual rating was evaluated using a newly introduced tool, 'vertical focus of resonance' (VFR), which focuses on the resonance energy in the frontal, throat, pharyngeal and nasal locations.ResultsThe NH group demonstrated a significantly lower nasalance score in the oral coupling and passage tasks than the HI group. Based on the results of nasalance correlation analysis, the HI group showed highly significant correlations between syllable and passage tasks, as contrasted with the NH group. There were significant differences in VFR between the nasalance types in both the NH and the HI groups.ConclusionThe HI hyper-nasal group showed tendencies of velopharyngeal opening, as opposed to the HI hypo-nasal group which showed tendencies of velopharyngeal closure. The HI mixed-nasal group showed inappropriate coordination of velopharyngeal function. In the HI group, the results of VFR showed that the air flow and the resonance energy were not released from the cavity of resonance. The suggested VFR tool explains the focusing characteristics of resonance energy within a continuation of speech sound regardless of the phonetic environment. Therefore, VFR may be a useful tool in explaining the deviant resonance patterns of HI individuals

Effects of grape pomace on the antioxidant defense system in diet-induced hypercholesterolemic rabbits

The effects of grape seeds extract and grape peels extract prepared from grape pomace on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue were investigated in rabbits fed on high cholesterol diet. New Zealand white rabbits were divided as follows ; 1) NOR (normal group); 2) CHOL (cholesterol group); 3) GSH (cholesterol + grape seed extract group); 4) GPE (cholesterol + grape peel extract); 5) GSP (cholesterol + grape seed powder); 6) GPP (cholesterol + grape peel powder); 7) GE (cholesterol + grape seed and peel extract); 8) GP (cholesterol + grape seed and peel powder). Eight groups of rabbits were studied for 8 weeks. At the end of the experimental period, rabbits were sacrificed and the liver tissue were removed. Then, GSH, GPx, GST, CAT and MDA in the liver were measured. In liver tissues, total glutathione contents (GSH), glutathione peroxidase (GPx) and catalase (CAT) activity, which was significantly higher by grape seed extract supplementation. The level of malondialdehyde (MDA) was lower in the serum of rabbits fed grape seed extract or grape peel powder plus cholesterol than in the serum of rabbits fed cholesterol alone. It is therefore likely that grape seed extract prepared from grape pomace functioned as antioxidants in vivo, negating the effects of the oxidative stress induced by 1% cholesterol diet. The grape seed extract was found effective in converting the oxidized glutathione into reduced glutathione, and in removing H2O2 that is created by oxidative stress. The grape peel powder was found to have small influence on reduced glutathione content, CAT and GPX activity, but it increased GST activity in liver tissues, resulting in promoting the combination of lipid peroxide and glutathione (GSH), and further, lowering the formation of lipid peroxide in the serum. Therefore, grape pomace (grape seed extract and grape peel powder) supplementation is considered to activate the antioxidant enzyme system and prevent damage with hypercholesterolemia

Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.

Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines and patient-derived tumor organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast cancer development through downregulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring of NELF-E-associated chromatin partners as a function of EMT and a co-option of NELF-E with the key EMT transcription factor SLUG. Accordingly, loss of NELF-E leads to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identify the histone acetyltransferase, KAT2B, as a key functional target of NELF-E-SLUG. Genetic and pharmacological inactivation of KAT2B ameliorate the expression of EMT markers, phenocopying NELF ablation. Elevated expression of NELF-E and KAT2B is associated with poorer prognosis in breast cancer patients, highlighting the clinical relevance of our findings. Taken together, we uncover a crucial role of the NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis