92 research outputs found

    Chemoenzymatic Synthesis of Glycosylated Macrolactam Analogues of the Macrolide Antibiotic YC‐17

    Full text link
    YC‐17 is a 12‐membered ring macrolide antibiotic produced from Streptomyces venezuelae ATCC 15439 and is composed of the polyketide macrolactone 10‐deoxymethynolide appended with D‐desosamine. In order to develop structurally diverse macrolactam analogues of YC‐17 with improved therapeutic potential, a combined approach involving chemical synthesis and engineered cell‐based biotransformation was employed. Eight new antibacterial macrolactam analogues of YC‐17 were generated by supplying a novel chemically synthesized macrolactam aglycone to S. venezuelae mutants harboring plasmids capable of synthesizing several unnatural sugars for subsequent glycosylation. Some YC‐17 macrolactam analogues were active against erythromycin‐resistant bacterial pathogens and displayed improved metabolic stability in vitro. The enhanced therapeutic potential demonstrated by these glycosylated macrolactam analogues reveals the unique potential of chemoenzymatic synthesis in antibiotic drug discovery and development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/1/adsc_201500250_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/2/2697_ftp.pd

    Lifestyle, dietary habits and consumption pattern of male university students according to the frequency of commercial beverage consumptions

    Get PDF
    Because excessive consumption of sugar-sweetened beverages may reduce the quality of nutritional intake, this study examined the consumption patterns of commercial beverages, lifestyle, dietary habits, and perception of sweet taste. Participants were 407 male university students in Kyeonggido, Korea, and information was collected by self-administered questionnaire. Among them, 58 nonsmokers volunteered to participate in the taste test. Participants were divided into three groups according to the frequency of commercial beverage consumptions: 120 rare (< 1 serving/week), 227 moderate (1-3 servings/week) and 133 frequent (> 3 servings/week) consumption groups. More subjects from the rare consumption group chose water, tea, and soy milk, and more from the frequent consumption group chose carbonated soft drinks and coffee (P = 0.031) as their favorite drinks. Frequent consumption group consumed fruit juice, coffee, and sports and carbonated soft drinks significantly more often (P = 0.002, P = 0.000, P = 0.000, respectively), but not milk and tea. Frequent consumption group consumed beverages casually without a specific occasion (P = 0.000) than rare consumption group. Frequent drinking of commercial beverages was associated with frequent snacking (P = 0.002), meal skipping (P = 0.006), eating out (P = 0.003), eating delivered foods (P = 0.000), processed foods (P = 0.001), and sweets (P = 0.002), and drinking alcoholic beverages (P = 0.029). Frequent consumption group tended to have a higher threshold of sweet taste without reaching statistical significance. The results provide information for developing strategies for evidence-based nutrition education program focusing on reducing consumption of unnecessary sugar-sweetened commercial beverages

    Independent effect of body mass index variation on amyloid-β positivity

    Get PDF
    ObjectivesThe relationship of body mass index (BMI) changes and variability with amyloid-β (Aβ) deposition remained unclear, although there were growing evidence that BMI is associated with the risk of developing cognitive impairment or AD dementia. To determine whether BMI changes and BMI variability affected Aβ positivity, we investigated the association of BMI changes and BMI variability with Aβ positivity, as assessed by PET in a non-demented population.MethodsWe retrospectively recruited 1,035 non-demented participants ≥50 years of age who underwent Aβ PET and had at least three BMI measurements in the memory clinic at Samsung Medical Center. To investigate the association between BMI change and variability with Aβ deposition, we performed multivariable logistic regression. Further distinctive underlying features of BMI subgroups were examined by employing a cluster analysis model.ResultsDecreased (odds ratio [OR] = 1.68, 95% confidence interval [CI] 1.16–2.42) or increased BMI (OR = 1.60, 95% CI 1.11–2.32) was associated with a greater risk of Aβ positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI variability. A greater BMI variability (OR = 1.73, 95% CI 1.07–2.80) was associated with a greater risk of Aβ positivity after controlling for age, sex, APOE e4 genotype, years of education, hypertension, diabetes, baseline BMI, and BMI change. We also identified BMI subgroups showing a greater risk of Aβ positivity.ConclusionOur findings suggest that participants with BMI change, especially those with greater BMI variability, are more vulnerable to Aβ deposition regardless of baseline BMI. Furthermore, our results may contribute to the design of strategies to prevent Aβ deposition with respect to weight control

    Suppression of CFTR-mediated Cl- Secretion of Airway Epithelium in Vitamin C-deficient Mice

    Get PDF
    Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (ΔIsc,amil), cAMP-dependent Cl- secretion (ΔIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (ΔIsc,ATP). In mice exposed to 98% PO2 for 36 hr, ΔIsc,forsk decreased, ΔIsc,amil and ΔIsc,ATP was not affected. In gulo(-/-) mice, both ΔIsc,forsk and ΔIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid

    Tristetraprolin inhibits the growth of human glioma cells through downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor mRNAs

    Get PDF
    Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3&apos; untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma
    corecore