17β-Estradiol up-regulates UDP-glucuronosyltransferase 1A9 expression via estrogen receptor α

AbstractUDP-glucuronosyltransferase 1A9 (UGT1A9) is a major phase II enzyme responsible for elimination of drugs and endogenous molecules. Clinical data have shown increased elimination of UGT1A9 substrates in pregnant women or oral contraceptive users, but the role of estrogen in the regulation of UGT1A9 expression remains unknown. In this study, we investigated the effect of 17β-estradiol (E2) on UGT1A9 expression and the role of ERα in the transcriptional regulation of UGT1A9. E2 significantly increased UGT1A9 promoter activity in HepG2 cells in the presence of ERα. UGT1A9 induction by E2 was abrogated by antiestrogen ICI182,780 in HepG2 cells that constitutively express ERα. Results from transient transfection of ERα mutants into HepG2 cells demonstrated that mutation at DNA-binding domain of ERα abrogates increased UGT1A9 promoter activity by E2. Deletion and mutation assays of UGT1A9 promoter revealed a putative ERE located within −2262/−1987 region. Examination of healthy human liver tissues revealed significantly higher UGT1A9 expression in women as compared to men. Together, these findings provide a mechanistic basis for the previous clinical reports and may shed a light on identifying sources for inter-individual variability in UGT1A9-mediated drug metabolism

EFFECTS OF LANDING HEIGHT ON LOWER EXTREMITY JOINT BIOMECHANICS DURING UNILATERAL AND BILATERAL LANDINGS

The aim of this study was to examine the lower extremity kinematics and kinetics during landing phase, in response to the effects of landing height during unilateral and bilateral landing. Ten young healthy male subjects (age: 26.1±1.8yr, height: 183.2±4.4cm, weight: 76.1±6.9kg) participated in this study. Each subject performed the unilateral and bilateral landing from a 30cm and 45cm wooden platform. The results showed the peak vertical ground reaction force (PVGRF) was increased during unilateral landing and at greater landing height (

The Genome Sequence of 'Mycobacterium massiliense' Strain CIP 108297 Suggests the Independent Taxonomic Status of the Mycobacterium abscessus Complex at the Subspecies Level

Members of the Mycabacterium abscessus complex are rapidly growing mycobacteria that are emerging as human pathogens. The M. abscassus complex was previously composed of three species, namely M. abscessus sensu strict, 'M. massiliense', and M. bolletii', In 2011, 'M. massiliense' and 'M. bolletre' were united and reclassified as a single subspecies within M. abscessus: M. abscessus subsp. bolletii. However, the placement of 'M. massiliense' Within the boundary of M. abscessus subsp. balletii remains highly controversial with regard to clinical aspects. In this study, we revisited the taxonomic status of members of the M. abscessus complex based on comparative analysis of he whole-genome sequences of 53 strains, The genome sequence of the previous type strain of 'Mycobacterium massiliense' (CIP 108297) was determined using next-generation sequencing. The genome tree based on average nucleotide identity (AN I) values supported the differentiation of M. bolletii' and M. massiliense' at the subspecies level. The genome tree also clearly illustrated that 'M. bolletil' and 'M. massiliense' form a distinct phylogenetic clade within the radiation of the M. abscessus complex. The genomic distances observed in this study suggest that the current M. abscessus subsp. bolletii taxon should be divided into two subspecies, M. abscessus subsp. massiliense subsp. nov. and M. abscessus subsp. bolletii, to correspondingly accommodate the previously known 'M. assiliense' and 'M. bolletii' strains.

Effect of 5-alpha Reductase Inhibitor on Storage Symptoms in Patients with Benign Prostatic Hyperplasia

Purpose Many patients with benign prostatic hyperplasia (BPH) have storage symptoms. The aim of this study was to evaluate the effects of treatment with a 5-alpha reductase inhibitor (5ARI) on storage symptoms in patients with BPH. Methods This study was conducted in 738 patients with lower urinary tract symptoms secondary to BPH. Patients with a prostate volume of higher than 30 mL on the transrectal ultrasound were classified into two groups: group A, in which an alpha blocker was solely administered for at least 12 months, and group B, in which a combination treatment regimen of an alpha blocker plus 5ARI was used. This was followed by an analysis of the changes in parameters such as the total International Prostate Symptom Score (IPSS), voiding symptom subscore, and storage symptom subscore between the two groups. In addition, we examined whether there was a significant difference between the two groups in the degree of change in storage symptoms between before and after the pharmacological treatment. Results Of the 738 men, 331 had a prostate volume ≥30 mL, including 150 patients in group A and 181 patients in group B. Total IPSS, the voiding symptom subscore, and the storage symptom subscore were significantly lower after treatment than before treatment in both groups (P<0.05). A comparison of the degree of change between before and after treatment, however, showed no significant differences in the storage symptom subscore between the two groups (P>0.05). Conclusions Alpha blocker and 5ARI combination treatment is effective for patients with BPH including storage symptoms. However, 5ARI does not exert a significant effect on storage symptoms in BPH patients

Autosomal Recessive Multiple Epiphyseal Dysplasia in a Korean Girl Caused by Novel Compound Heterozygous Mutations in the DTDST (SLC26A2) Gene

Multiple epiphyseal dysplasia is caused by heterogenous genotypes involving more than six genes. Recessive mutations in the DTDST gene cause a phenotype of recessive multiple epiphyseal dysplasia (rMED). The authors report a 9-yr old Korean girl with the rMED phenotype having novel compound heterozygous mutations in the DTDST gene, which were inherited from both parents. This is the first Korean rMED case attributed to DTDST mutations, and expands the spectrum of diseases caused by DTDST mutations

Time-resolved pathogenic gene expression analysis of the plant pathogen Xanthomonas oryzae pv. oryzae

Virulence of wild-type and mutant Xoo strains on rice. (DOCX 16 kb

Examining the links between burnout and suicidal ideation in diverse occupations

IntroductionIt is uncertain whether burnout is associated with suicidal ideation among workers not in health care services. The aim of this study was to identify how burnout and suicidal ideation are linked among employees in various occupations and whether depression affects this link.MethodsThis cross-sectional study collected data from 12,083 participants aged 19–65 years from 25 companies and public institutions who underwent workplace mental health screening. Burnout and depression were assessed using both the Oldenburg Burnout Inventory and the Center for Epidemiologic Studies Depression Scale. Suicidal ideation was assessed by a self-rated questionnaire from the Korea National Health and Nutrition Examination Survey.ResultsExhaustion but not the cynicism dimension of burnout was associated with increased odds of suicidal ideation after adjustment for depression and other covariates (odds ratio [OR] = 1.47, 95% CI = 1.26–1.72). The association of exhaustion with suicidal ideation was significant in both depressed (OR = 1.36, 95% CI = 1.14–1.61) and not depressed (OR = 1.77, 95% CI = 1.13–2.76) participants. In exhausted participants, insufficient job control, an unfavorable occupational climate, low educational level, and depression were associated with increased odds of suicidal ideation.ConclusionExhaustion is linked with risk of suicidal ideation in employees not in health care service, regardless of depression status. Exhausted employees, particularly those having poor job resources, should be recognized as an at-risk group