Mutagenesis of conserved region I in the DNA polymerase from human adenovirus serotype 2

The functional importance of the conserved region I (YGDTDSLF) found in several prokaryotic, eukaryotic, and viral DNA polymerases has been probed by site-directed mutagenesis of the adenovirus DNA polymerase (Ad Pol). Three different adenovirus-specific assays have been used to measure the in vitro activity of region I mutants of Ad Pol expressed in transiently transfected CMT-4 cells. In general, both conservative and nonconservative changes generally showed a greater than 5- to 10-fold reduction in activity in three different assays for activity. However, several replacements at the glycine residue showed activities closer to wild-type levels. For example, replacements of this glycine with cysteine (found in bacteriophage phi 29, another protein primed replication system), with serine, or with methionine had little effect on the activity observed in adenovirus-specific assays, such as initiation and elongation. These studies confirm the importance of this region of Ad Pol in specific initiation and elongation reactions on Ad DNA templates.     

Effect of biphenyl dimethyl dicarboxylate on the cellular and nonspecific immunosuppressions by ketoconazole in mice

The effect of biphenyl dimethyl dicarboxylate (PMC) on the cellular and nonspecific immunosuppressions by ketoconazole (KCZ) was investigated in ICR mice. PMC at a dose of 6 mg/kg was administered orally to mice daily for 14 consecutive days. KCZ was suspended in RPMI 1640 medium and orally administered at 160 mg/kg/day 2 hrs after the administration of PMC. Immune responses of the delayed-type hypersensitivity (DTH) reaction to sheep red blood cells (SRBC), phagocytic activity and natural killer (NK) cell activity were evaluated. DTH reaction to SRBC was enhanced to normal level by the combination of PMC and KCZ, compared with treatment of KCZ alone. In the combination of PMC and KCZ, as compared with the treatment of KCZ alone, there were also significant increases in activities of natural killer (NK) cells and phagocytes along with circulating leukocytes. These findings indicate that PMC shows a significant restoration from the immunotoxic status induced by KCZ.     

Diphenhydramine produces local cutaneous analgesia in response to dorsal skin noxious stimuli in the rat

Although diphenhydramine has been shown to produce longer duration of spinal block than lidocaine, few studies disclose its skin infiltrative anesthesia when compared with a long‐lasting local anesthetic, bupivacaine. The purpose of this study was to investigate whether diphenhydramine elicited cutaneous analgesia in comparison with bupivacaine. After inhibition of cutaneous trunci muscle reflex via subcutaneous injection of drugs in rats, we examined the local anesthetic effect of diphenhydramine and bupivacaine as infiltrative cutaneous analgesia in a dose‐dependent fashion. We showed that diphenhydramine, as well as bupivacaine displayed a dose‐dependent cutaneous analgesia in response to dorsal cutaneous noxious stimuli. The relative potency (50% effective dose) was bupivacaine (0.023 [0.013–0.035]%) > diphenhydramine (0.078 [0.068–0.091]%; P < 0.001). On an equipotent basis, diphenhydramine had a similar duration of action to bupivacaine. Neither local injection of saline nor intraperitoneal administration of a large dose of diphenhydramine or bupivacaine produced cutaneous analgesia (data not shown). We conclude that diphenhydramine is less potent than bupivacaine at producing cutaneous analgesia. At equipotent doses for infiltrative cutaneous analgesia, the duration of action of diphenhydramine is equal to that of bupivacaine.     

2-D08 treatment regulates C2C12 myoblast proliferation and differentiation via the Erk1/2 and proteasome signaling pathways

Journal of Muscle Research and Cell Motility - SUMOylation is one of the post-translational modifications that involves the covalent attachment of the small ubiquitin-like modifier (SUMO) to the...     

Frequency of Consumption of Whole Fruit,Not Fruit Juice,Is Associated with Reduced Prevalence of Obesity in Korean Adults

BackgroundFruit consumption is known to be beneficial to health. However, the health benefits of fruit juice are controversial due to its high sugar content.ObjectivesTo examine the associations of frequency of consumption of whole fruit and fruit juice with obesity and metabolic syndrome.DesignThis cross-sectional study used data from the 2012-2015 Korea National Health and Nutrition Examination Survey.ParticipantsA total of 10,460 adults (4,082 men and 6,378 women) aged 19 to 64 years were included in the study.Main outcome measuresFrequency of consumption of whole fruit and fruit juice was evaluated using a food frequency questionnaire, and dietary sugar intake was calculated using a 24-hour recall. Obesity and abdominal obesity were determined using body mass index and waist circumference, respectively. Metabolic syndrome was defined on the basis of the National Cholesterol Education Program Adult Treatment Panel III.Statistical analyses performedMultiple logistic regression analysis was performed to examine the associations between frequency of whole fruit or fruit juice consumption and obesity and metabolic syndrome abnormalities.ResultsThe percentage of participants who consumed whole fruit daily was 32.6%, whereas 52.3% consumed fruit juice rarely. The average intake of total sugars was 14.9% of total energy, which was within the recommend range (<20% of total energy) for Koreans. Consuming whole fruit ≥1 time/day was associated with reduced prevalence of obesity, abdominal obesity, and elevated blood pressure compared with consuming whole fruit ≤1 time/wk. However, frequency of fruit juice consumption showed no association with obesity, abdominal obesity, and metabolic syndrome.ConclusionsFrequency of whole fruit consumption was associated with reduced prevalence of obesity and metabolic syndrome abnormalities among Korean adults with average total sugar intake within the recommended range.     

Effectiveness and safety of single transseptal ablation for atrial fibrillation in real‐word practice

BackgroundWe have previously reported that unilateral groin‐single transseptal (ST) ablation in patients with paroxysmal atrial fibrillation (AF) was safe and significantly reduced patient discomfort compared with bilateral groin‐double transseptal (DT) ablation.HypothesisIn the present study, we hypothesized that ST ablation would be as effective and safe as DT ablation in real‐world practice like previous study. Among the 1765 consecutive patients in the Yonsei AF ablation cohort from October 2015 to January 2020, 1144 patients who underwent radiofrequency ablation were included for the analysis. Among them, 450 underwent ST ablation and 694 underwent DT ablation.ResultsThe total procedure time, ablation time, and fluoroscopy time were longer in the ST group than in the DT group (p < .05 for all). The hospital stay after catheter ablation was 1.3 ± 1.1 days which was longer in DT group than ST group (p = .001). No significant difference was observed in the complication rate (p = .263) and AF‐free survival rate (log‐rank p = .19) between the groups. However, after excluding patients who used antiarrhythmic drugs when AF recurred, the AF‐free survival rates were lower in the DT group than in the ST group before and after propensity score matching (log‐rank p = .026 and .047, respectively).ConclusionAlthough the ST approach increases the procedure time compared with the DT approach owing to the need for more frequent catheter exchanges, the ST approach is a feasible and safe strategy for AF ablation in terms of rhythm outcomes and risk of complications.     

Hypoxia drives transient site-specific copy gain and drug-resistant gene expression

Copy number heterogeneity is a prominent feature within tumors. The molecular basis for this heterogeneity remains poorly characterized. Here, we demonstrate that hypoxia induces transient site-specific copy gains (TSSGs) in primary, nontransformed, and transformed human cells. Hypoxia-driven copy gains are not dependent on HIF1α or HIF2α; however, they are dependent on the KDM4A histone demethylase and are blocked by inhibition of KDM4A with a small molecule or the natural metabolite succinate. Furthermore, this response is conserved at a syntenic region in zebrafish cells. Regions with site-specific copy gain are also enriched for amplifications in hypoxic primary tumors. These tumors exhibited amplification and overexpression of the drug resistance gene CKS1B, which we recapitulated in hypoxic breast cancer cells. Our results demonstrate that hypoxia provides a biological stimulus to create transient site-specific copy alterations that could result in heterogeneity within tumors and cell populations. These findings have major implications in our understanding of copy number heterogeneity and the emergence of drug resistance genes in cancer.