Combined Effect of Body Mass Index and Waist Circumference in Predicting Nonalcoholic Fatty Liver Disease.

Background: Body mass index (BMI) and waist circumference (WC) are the most widely used anthropometric indices for identifying obesity. This study aimed to compare and clarify the usefulness of BMI, WC, and the combination of these two indicators in predicting nonalcoholic fatty liver disease (NAFLD). Methods: This cross-sectional study included 15,267 Korean adults. We defined four obesity categories using BMI and WC as follows: BMI nonobese and WC nonobese (BNWN); BMI obese and WC nonobese (BOWN); BMI nonobese and WC obese (BNWO); and BMI obese and WC obese (BOWO). Analysis of variance was used to compare fatty liver severity across each category. The odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated using multiple logistic regression. Results: Compared with BNWN, participants with BNWO were 3.235 (95% CI: 2.774-3.773) times more likely and participants with BOWN were 2.344 (95% CI: 2.045-2.687) times more likely to have NAFLD. Participants with BNWO had higher OR for NAFLD than those with BOWN. Moreover, BOWO participants had the highest OR of 4.788 (95% CI: 4.350-5.270) for NAFLD among all obesity categories. Conclusion: Combined obesity classification by BOWO is the most reliable indicator for NAFLD presence in Korean adults.

Triglyceride Glucose-Waist Circumference (TyG-WC) Is a Reliable Marker to Predict Non-Alcoholic Fatty Liver Disease.

The triglyceride and glucose index (TyG index), a marker of insulin resistance, is positively associated with NAFLD. Modified TyG indices, combining body composition markers including body-mass index (BMI) or waist circumference (WC) with the TyG index, are reported to enhance predictability of insulin resistance. This study aimed to compare the usefulness of modified TyG indices for predicting NAFLD with the TyG index and fatty liver index (FLI). This cross-sectional study included 12,757 Korean adults. The TyG index and FLI were calculated using established formulas, and TyG-BMI and TyG-WC were calculated as TyG × BMI and TyG × WC, respectively. All measures were divided into quartiles. NAFLD severity (grade 0-3) was compared using ANOVA by quartiles of each index. Odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated using a multiple logistic regression analysis. ROC and AUROC analyses were performed to compare the predictability of NAFLD using WC, BMI, TyG, TyG-BMI, TyG-WC, and FLI. A higher TyG index, TyG-BMI, TyG-WC, and FLI were associated with a higher grade of NAFLD. ORs (CIs) for NAFLD increased in all indices, especially in TyG-WC (39.251 (31.304-49.215)) and FLI (38.937 (31.145-48.678)). AUROC was 0.848 (0.840-0.855) for TyG-WC and 0.850 (0.842-0.857) for FLI. TyG-WC is a reliable indicator for the presence of NAFLD in Korean adults.

Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis.

BACKGROUND: Milbemycins, produced from Streptomyces hygroscopicus subsp. aureolacrimosus and Streptomyces bingchenggensis, are 16-membered macrolides that share structural similarity with avermectin produced from Streptomyces avermitilis. Milbemycins possess strong acaricidal, insecticidal, and anthelmintic activities but low toxicity. Due to the high commercial value of the milbemycins and increasing resistance to the avermectins and their derivatives, it is imperative to develop an efficient combinatorial biosynthesis system exploiting an overproduction host strain to produce the milbemycins and novel analogs in large quantities. RESULTS: The respective replacement of AveA1 and AveA3 (or module 7 in AveA3) of the avermectin polyketide synthase (PKS) in the avermectin high-producing strain S. avermitilis SA-01 with MilA1 and MilA3 (or module 7 in MilA3) of the milbemycin PKS resulted in the production of milbemycins A3, A4, and D in small amounts and their respective C5-O-methylated congener milbemycins B2, B3, and G as major products with total titers of approximately 292 mg/l. Subsequent inactivation of the C5-O-methyltransferase AveD led to a production of milbemycins A3/A4 (the main components of the commercial product milbemectin) in approximately 225 and 377 mg/l in the flask and 5 l fermenter culture, respectively, along with trace amounts of milbemycin D. CONCLUSIONS: We demonstrated that milbemycin biosynthesis can be engineered in the avermectin-producing S. avermitilis by combinatorial biosynthesis with only a slight decrease in its production level. Application of a similar strategy utilizing higher producing industrial strains will provide a more efficient combinatorial biosynthesis system based on S. avermitilis for further enhanced production of the milbemycins and their novel analogs with improved insecticidal potential.

Metabolic engineering of rational screened Saccharopolyspora spinosa for the enhancement of spinosyns A and D production.

Spinosyns A and D are potent ingredient for insect control with exceptional safety to non-target organisms. It consists of a 21-carbon tetracyclic lactone with forosamine and tri-O-methylated rhamnose which are derived from S-adenosylmethionine. Although previous studies have revealed the involvement of metK1 (S-adenosylmethionine synthetase), rmbA (glucose-1-phosphate thymidylyltransferase), and rmbB (TDP-D-glucose-4, 6-dehydratase) in the biosynthesis of spinosad, expression of these genes into rational screened Saccharopolyspora spinosa (S. spinosa MUV) has not been elucidated till date. In the present study, S. spinosa MUV was developed to utilize for metabolic engineering. The yield of spinosyns A and D in S. spinosa MUV was 244 mg L(-1) and 129 mg L(-1), which was 4.88-fold and 4.77-fold higher than that in the wild-type (50 mg L(-1) and 27 mg L(-1)), respectively. To achieve the better production; positive regulator metK1-sp, rmbA and rmbB genes from Streptomyces peucetius, were expressed and co-expressed in S. spinosa MUV under the control of strong ermE* promoter, using an integration vector pSET152 and expression vector pIBR25, respectively. Herewith, the genetically engineered strain of S. spinosa MUV, produce spinosyns A and D up to 372/217 mg L(-1) that is 7.44/8.03-fold greater than that of wild type. This result demonstrates the use of metabolic engineering on rationally developed high producing natural variants for the production.

Characterization of the structure and immunostimulatory activity of a vaccine adjuvant, de-O-acylated lipooligosaccharide.

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. LPS elicits strong immunopathological responses during bacterial infection, and the lipid A moiety of LPS is responsible for this immunostimulatory activity. Lipid A exerts its biological activity by sending signals via TLR4 present on immune cells, and TLR4 agonists have been a target for vaccine adjuvant. Previously, we demonstrated an adjuvant activity of deacylated lipooligosaccharide (dLOS) to viral and bacterial antigens. In this study, we characterized the chemical structure of dLOS and evaluated its immunostimulatory activity on mouse and human immune cells in comparison with monophosphoryl lipid A (MPL). dLOS consists of the R3-type core, a glucosamine disaccharide with two phosphate groups, and two N-linked acyl groups [corrected], and two N-linked acyl groups. dLOS was similar to MPL in induction of cytokine production in mouse peritoneal macrophages, but was a more potent activator in human monocytes and dendritic cells (DCs). Results of an analysis of allogeneic T cell responses revealed that dLOS induces Th1, Th2, and Th17-type immune responses in a dose-dependent manner. The immunostimulatory activities of dLOS were completely abrogated in TLR4(-/-) mice, which confirms its TLR4-dependency. These results suggest that in the presence of the core oligosaccharide, O-linked acyl groups of LPS are dispensable for activating the TLR4 signaling pathway. dLOS did not cause any pathological effects or death at 0.25, 0.5, or 1 mg per kg body weight in mice in the acute toxicity tests. This result suggests that dLOS has a low toxicity. dLOS should be considered for further development as a safe and effective adjuvant for human vaccines.

Effects of coenzyme Q10 on arterial stiffness, metabolic parameters, and fatigue in obese subjects: a double-blind randomized controlled study.

This study investigated the effects of coenzyme Q(10) supplementation on metabolic parameters, inflammatory markers, arterial stiffness, and fatigue in obese subjects. We performed a randomized, double-blind, placebo-controlled, single-center study on 51 obese subjects with a body mass index (BMI) of ≥25 kg/m(2). Subjects were randomized into either a coenzyme Q(10) (200 mg/day) group (n = 26, BMI = 27.9 ± 2.3 kg/m(2), age = 42.7 ± 11.3 years) or a placebo group (n = 25, BMI = 26.8 ± 2.8 kg/m(2), age = 41.3 ± 11.2 years) for a 12-week study. We collected anthropometric measurements, blood for laboratory testing, brachial-ankle pulse wave velocity (baPWV) as an indicator of arterial stiffness, and responses to a fatigue severity scale (FSS) questionnaire at the initial (0 week) and final (12 weeks) visits. A total of 36 subjects successfully completed the study protocol. Serum coenzyme Q(10) levels increased significantly from 0.65 ± 0.27 µg/mL to 1.20 ± 0.38 µg/mL in the coenzyme Q(10) group (P < .001). Oral administration of coenzyme Q(10) did not significantly affect lipid profiles, oxidative and inflammatory markers [including lipoprotein (a), oxidized low-density lipoprotein level, C-reactive protein, and white blood cell count], or baPWV. The mean FSS score decreased significantly from 40.1 to 33.1 in the coenzyme Q(10) group (P = .017), but no significant change was seen in the placebo group (P = .464). However, the extents of the change in mean FSS score between the placebo and coenzyme Q(10) groups were not significantly different (P = .287). In conclusion, we found no evidence that coenzyme Q(10) affects fatigue index, arterial stiffness, metabolic parameters, or inflammatory markers.

The major catalase gene (katA) of Pseudomonas aeruginosa PA14 is under both positive and negative control of the global transactivator OxyR in response to hydrogen peroxide.

The adaptive response to hydrogen peroxide (H(2)O(2)) in Pseudomonas aeruginosa involves the major catalase, KatA, and OxyR. However, neither the molecular basis nor the relationship between the aforementioned proteins has been established. Here, we demonstrate that the transcriptional activation of the katA promoter (katAp) in response to H(2)O(2) was abrogated in the P. aeruginosa PA14 oxyR null mutant. Promoter deletion analyses revealed that H(2)O(2)-mediated induction was dependent on a region of DNA -76 to -36 upstream of the H(2)O(2)-responsive transcriptional start site. This region harbored the potential operator sites (OxyR-responsive element [ORE]) of the Escherichia coli OxyR binding consensus. Deletion of the entire ORE not only abolished H(2)O(2)-mediated induction but also elevated the basal transcription, suggesting the involvement of OxyR and the ORE in both transcriptional activation and repression. OxyR bound to the ORE both in vivo and in vitro, demonstrating that OxyR directly regulates the katAp. Three distinct mobility species of oxidized OxyR were observed in response to 1 mM H(2)O(2), as assessed by free thiol trapping using 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid. These oxidized species were not observed for the double mutants with mutations in the conserved cysteine (Cys) residues (C199 and C208). The uninduced transcription of katAp was elevated in an oxyR mutant with a mutation of Cys to serine at 199 (C199S) and even higher in the oxyR mutant with a mutation of Cys to alanine at 199 (C199A) but not in oxyR mutants with mutations in C208 (C208S and C208A). In both the C199S and the C208S mutant, however, katAp transcription was still induced by H(2)O(2) treatment, unlike in the oxyR null mutant and the C199A mutant. The double mutants with mutations in both Cys residues (C199S C208S and C199A C208S) did not differ from the C199A mutant. Taken together, our results suggest that P. aeruginosa OxyR is a bona fide transcriptional regulator of the katA gene, sensing H(2)O(2) based on the conserved Cys residues, involving more than one oxidation as well as activation state in vivo.