Genetically Encoded Sensor Cells for the Screening of Glucocorticoid Receptor (GR) Effectors in Herbal Extracts.

Although in vitro sensors provide facile low-cost ways to screen for biologically active targets, their results may not accurately represent the molecular interactions in biological systems. Cell-based sensors have emerged as promising platforms to screen targets in biologically relevant environments. However, there are few examples where cell-based sensors have been practically applied for drug screening. Here, we used engineered cortisol-detecting sensor cells to screen for natural mimetics of cortisol. The sensor cells were designed to report the presence of a target through signal peptide activation and subsequent fluorescence signal translocation. The developed sensor cells were able to detect known biological targets from human-derived analytes as well as natural product extracts, such as deer antlers and ginseng. The multi-use capability and versatility to screen in different cellular environments were also demonstrated. The sensor cells were used to identify novel GR effectors from medicinal plant extracts. Our results suggest that decursin from dongquai had the GR effector function as a selective GR agonist (SEGRA), making it a potent drug candidate with anti-inflammatory activity. We demonstrated the superiority of cell-based sensing technology over in vitro screening, proving its potential for practical drug screening applications that leads to the function-based discovery of target molecules.

Rapid Screening of Glucocorticoid Receptor (GR) Effectors Using Cortisol-Detecting Sensor Cells.

Cortisol, a stress hormone, plays key roles in mediating stress and anti-inflammatory responses. As abnormal cortisol levels can induce various adverse effects, screening cortisol and cortisol analogues is important for monitoring stress levels and for identifying drug candidates. A novel cell-based sensing system was adopted for rapid screening of cortisol and its functional analogues under complex cellular regulation. We used glucocorticoid receptor (GR) fused to a split intein which reconstituted with the counterpart to trigger conditional protein splicing (CPS) in the presence of targets. CPS generates functional signal peptides which promptly translocate the fluorescent cargo. The sensor cells exhibited exceptional performance in discriminating between the functional and structural analogues of cortisol with improved sensitivity. Essential oil extracts with stress relief activity were screened using the sensor cells to identify GR effectors. The sensor cells responded to peppermint oil, and L-limonene and L-menthol were identified as potential GR effectors from the major components of peppermint oil. Further analysis indicated L-limonene as a selective GR agonist (SEGRA) which is a potential anti-inflammatory agent as it attenuates proinflammatory responses without causing notable adverse effects of GR agonists.

The Health Status of Informal Waste Collectors in Korea.

Background: A broad, holistic approach was performed among informal waste collectors (IWCs) in Korea to understand their complex multidimensional health and safety problems. Methods: In the quantitative study, a survey of IWCs was conducted at four junk shops in Gangbuk-gu, Seoul, and survey data were used to calculate age-standardized prevalence rates based on comparisons with the general population in Korea. A qualitative study was also performed to provide more details on IWCs' occupational and musculoskeletal injuries and depression. Results: In the quantitative study, the age-standardized prevalence rate (aSPR) of occupational injury was higher than that of the general standard population (aSPR: 10.42, 95% confidence interval (CI) 5.19-18.64) and that of blue-collar workers (aSPR: 4.65, 95% CI 2.32-8.32). Regarding musculoskeletal problems, compared to employed populations, the aSPRs of shoulder pain (aSPR: 2.63, 95% CI 1.60-4.06), wrist pain (aSPR: 3.33, 95% CI 1.33-6.86), knee pain (aSPR: 1.51, 95% CI 1.01-2.17), and ankle pain (aSPR: 3.54, 95% CI 1.14-8.26) were higher. Regarding psychological problems, depression (aSPR: 2.55, 95% CI 1.27-4.56) and suicidal or self-harm ideation (aSPR: 2.09, 95% CI 1.11-3.58) were higher compared to general populations. Through the qualitative study and case study on muscular problems, more details on the work environment problems of IWCs were obtained. Conclusions: IWCs are exposed to various occupational hazards and lack proper protection. They show a high prevalence of occupational injury, musculoskeletal disease, and depression.

Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean Multicenter Cancer Cohort.

BACKGROUND: The role of soybean products in gastric cancer risk is not clear in epidemiologic studies due to measurement error from dietary intake questionnaires and due to different degrees of bias according to study design. To examine the association between soybean products and gastric cancer risk, we measured phytoestrogen biological markers in a nested case-control study. METHODS: The study population was composed of 131 cases and 393 matched controls within the Korean Multicenter Cancer Cohort. The concentrations of the four biomarkers in the plasma samples were measured using time-resolved fluoroimmunoassay. Conditional and unconditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Median plasma concentrations of genistein (229 nmol/L for controls, 181.8 nmol/L for cases; P=0.07) and daidzein (131.2 nmol/L for controls, 80.5 nmol/L for cases; P=0.04) in cases were lower than in controls, whereas equol concentrations were similar. Compared with the reference group, gastric cancer risk decreased in the highest groups for genistein (OR, 0.54; 95% CI, 0.31-0.93) and daidzein (OR, 0.21; 95% CI, 0.08-0.58). Higher equol concentrations were associated with a decreased risk for gastric cancer (OR, 0.50; 95% CI, 0.27-0.90). The combination of the highest concentrations for each isoflavone category was associated with a 0.09-fold decreased risk for gastric cancer compared with the combination of the lowest concentrations for each category. There was no association between plasma lignan concentrations and gastric cancer. CONCLUSIONS: High serum concentrations of isoflavones were associated with a decreased risk for gastric cancer. IMPACT: These results suggest a beneficial effect of high soybean product intake for gastric cancer risk.