Regulation of cytochrome P450 mRNA expression in primary porcine hepatocytes by selected secondary plant metabolites from chicory (Cichorium intybus L.)

Chicory (Cichorium intybus) has been shown to induce enzymes of pharmacokinetic relevance (cytochrome P450; CYP). The aim of this study was to investigate the effects of selected secondary plant metabolites with a global extract of chicory root, on the expression of hepatic CYP mRNA (1A2, 2A19, 2C33, 2D25, 2E1 and 3A29), using primary porcine hepatocytes. Of the tested secondary plant metabolites, artemisinin, scoparone, lactucin and esculetin all induced increased expression of specific CYPs, while esculin showed no effect. In contrast, a global extract of chicory root decreased the expression of CYP1A2, 2C33, 2D25 and 3A29 at high concentrations. The results suggest that purified secondary metabolites from chicory affect CYP expression and thereby might affect detoxification in general, and that global extracts of plants can have effects different from individual components

An update on immune checkpoint therapy for the treatment of lynch syndrome

During the recent years, immune checkpoint-based therapy has proven highly effective in microsatellite instable (MSI) solid tumors irrespective of organ site. MSI tumors are associated with a defective mismatch repair (MMR) system and a highly immune-infiltrative tumor microenvironment—both characteristics of Lynch syndrome. Lynch syndrome is a multi-tumor syndrome that not only confers a high risk of colorectal and endometrial cancer but also cancer in, eg the upper urinary tract, ovaries, and small bowel. Since the genetic predisposition for Lynch syndrome are pathogenic variants in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2, most of the Lynch syndrome cancers show MMR deficiency, MSI, and activation of the immune response system. Hence, Lynch syndrome cancer patients may be optimal candidates for immune checkpoint-based therapies. However, molecular differences have been described between sporadic MSI tumors (developed due to MLH1 promoter hypermethylation) and Lynch syndrome tumors, which may result in different treatment responses. Furthermore, the response profile of the rare Lynch syndrome cases may be masked by the more frequent cases of sporadic MSI tumors in large clinical trials. With this review, we systematically collected response data on Lynch syndrome patients treated with FDA- and EMA-approved immune checkpoint-based drugs (pembrolizumab, atezolizumab, durvalumab, avelumab, ipilimumab, and nivolumab) to elucidate the objective response rate and progression-free survival of cancer in Lynch syndrome patients. Herein, we report Lynch syndrome-related objective response rates between 46 and 71% for colorectal cancer and 14–100% for noncolorectal cancer in unselected cohorts as well as an overview of the Lynch syndrome case reports. To date, no difference in the response rates has been reported between Lynch syndrome and sporadic MSI cancer patients

School-related mediators in social inequalities in smoking: a comparative cross-sectional study of 20,399 adolescents

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the associations between social inequalities and daily smoking among 13 and 15 year olds, and to determine the role of students' academic achievement and school satisfaction in these associations.</p> <p>Methods</p> <p>HBSC is an international study including adolescents from 32 countries in Europe, Israel, and North America. The present study was based on information from 20,399 adolescents from Denmark, Sweden, Norway, Finland and the United Kingdom. Data were analysed by regression models.</p> <p>Results</p> <p>The initial analyses showed significant inequality in daily smoking in all countries except for Sweden. When adjusted for the mediating role of academic achievement, estimates were attenuated, but remained significant in three countries.</p> <p>Conclusion</p> <p>The study found social inequality in daily smoking in Denmark, Sweden, Norway, Finland and United Kingdom, as well as inequalities in students' academic achievement and school satisfaction. The analyses also showed that above average academic achievement was associated with lower OR of smoking. Teachers and politicians may find this information useful, and allocate resources to give higher priority to a supportive environment in schools especially for children and adolescents in lower social groups. Subsequently this prioritisation might contribute to reducing smoking in this group.</p

Association between Hashimoto's Thyroiditis and Thyroid Cancer in 64,628 Patients

BACKGROUND: The incidence of thyroid cancer (TC) is increasing although explanatory causes are lacking. A link between cancer and inflammation is well documented but unclear for autoimmune thyroid diseases and TC. We aimed to systematically review the association between Hashimoto’s thyroiditis (HT) and papillary, follicular, medullary, anaplastic thyroid carcinoma, and thyroid lymphoma (TL). METHODS: PubMed, OVID Medline, Google Scholar, and the Cochrane Library were searched from 1955 to 2016. The inclusion criteria were age >18 years, ≥20 cases of HT or TC. We collectively examined the incidence of HT in TC and of TC in HT. RESULTS: We identified 36 studies (64,628 subjects) published between 1955 and 2016 from 13 countries. We found a relative risk (RR) of HT among papillary thyroid cancer (PTC) of 2.36 [95% confidence intervals (CIs) 1.55–3.29, p < 0.001], an RR of PTC among HT of 1.40 (95% CI 1.07–1.85, p = 0.016), and an RR of TL among HT of 9.74 (95% CI 3.93–24.13, p < 0.001). CONCLUSION: We report an association between HT and PTC and between HT and TL. No association was found between HT and follicular, medullary, or anaplastic thyroid cancer

Self-Reported Health as Predictor of Allostatic Load and All-Cause Mortality: Findings From the Lolland-Falster Health Study

Objectives: The aim was to determine the association between self-reported health (SRH), allostatic load (AL) and mortality.Methods: Data derived from the Lolland-Falster Health Study undertaken in Denmark from 2016–2020 (n = 14,104). Median follow-up time for death was 4.6 years where 456 participants died. SRH was assessed with a single question and AL by an index of ten biomarkers. Multinomial regression analysis were used to examine the association between SRH and AL, and Cox regression to explore the association between SRH, AL and mortality.Results: The risk of high AL increased by decreasing level of SRH. The ratio of relative risk (RRR) of having medium vs. low AL was 1.58 (1.11–2.23) in women reporting poor/very poor SRH as compared with very good SRH. For men it was 1.84 (1.20–2.81). For high vs. low AL, the RRR was 2.43 (1.66–3.56) in women and 2.96 (1.87–4.70) in men. The hazard ratio (HR) for all-cause mortality increased by decreasing SRH. For poor/very poor vs. very good SRH, the HR was 6.31 (2.84–13.99) in women and 3.92 (2.12–7.25) in men.Conclusion: Single-item SRH was able to predict risk of high AL and all-cause mortality

Naturvidenskabelige undersøgelser af mursten i Sorø Klosterkirke – sortering af mursten

Faculty surveys of bricks in Sorø Abbey – sorting of bricksBy Kaare Lund Rasmussen, Christina Andersenand Thomas BertelsenSmall samples have been procured with hammer and chisel from the bricks in the crowns of the walls in the medieval church of the Cistercian monastery of Sorø, Denmark. The samples have been subjected to three types of analyses: magnetic susceptibility, thermoluminescence sensitivity, and for the first time colour measurements. The colour measurements were performed with a handheld Minolta CM-2600d photo spectrometer yielding very precise colours in the 1976 CIE colour system (L*,a*,b*). Extensive sorting of bricks according to colour seems to have been a common feature in the vast group of Danish late medieval building projects where the varying colours of bricks were used as decoration. Genuine patterns seem to be a phenomenon of eastern Denmark with Roskilde Cathedral’s Chapel of the Three Kings from about 1460 as the noblest representative (fig. 13). Masonry with belts of bricks of contrasting colours also occurs, while arches of alternating red and dark bricks appear across the country (fig. 14). The most common type of decoration, however, was red façades with evenly spread dark bricks. This might seem coincidental but the absence of this feature in the interior walls underlines its role as a deliberate facade décor. Possibly, bricks were also sorted by colour when the building of the Abbey Church of Sorø was commenced shortly after the founding of the abbey in 1161. Only small parts of the original façade of the church have been preserved, for example the gable of the northern transept, which is a well-balanced blend of red and dark bricks (see fig. 15, p. 118). In contrast, the interior walls above the vaulting are built of much more monochrome bricks, which points to a deliberate wish for polychrome façades