Friedrichsenkloster5453

00, p = 0.91). Advanced adenomas (OR1.05, p = 0.63) and serrated polyps (RR1.03, p = 0.63) were also not significantly inversely associated with Vit-D supplementation. Our study shows that Vit-D does not seem to have a role in the chemoprevention of colorectal neoplasms. However, additional well-designed studies are needed in order to draw safe conclusions. A potentially beneficial role of Vit-D supplementation in CRC primary prevention in individuals with severe vitamin D deficiency as well in the primary prevention of early-onset CRC, requires further investigation.

The healthy migrant and salmon bias hypotheses stipulate that those who are healthier are more likely to migrate (a selection effect) and unhealthy migrants have a greater tendency to return to their origin communities than healthier migrants. It remains unclear whether the hypotheses are relevant for mental health, although they have robust evidence for physical health. The current study expands the theoretical foundation underlying these hypotheses by exploring the impact of migration status on depression among the middle-aged and older population in China.

Longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013, 2015 and 2018 were used. Participants were divided into three groups, non-migrants, permanent migrants, and return-migrants according to their migration status. The Chinese version of 10-item Center for Epidemiologic Studies Depression Scale was used to assess clinically relevant depressive symptoms. Incidence were estimated by each migration status and lly among permanent migrants who have migrated and converted Hukou from their original registration place to their current residence.The myocardial fibrosis in response to myocardial infarction (MI) is closely related to the dysbalance of endothelial-to-mesenchymal transition (EndMT). Although numerous reports indicate that α7 nicotinic acetylcholine receptor (α7nAChR) activates the cholinergic anti-inflammatory pathway (CAP) to regulate the magnitude of inflammatory responses, the role of α7nAChR in myocardial fibrosis, as well as the underlying mechanisms, have not been elucidated. In this study, we evaluated cardiac function, fibrosis, and EndMT signaling using a mouse model of MI and interleukin (IL)-1β-induced human cardiac microvascular endothelial cells (HCMECs). In vivo, α7nAChR deletion increased cardiac dysfunction, exacerbated the cardiac inflammatory response, and NF-κB activation, and enhanced EndMT, as shown by higher expression levels of fibroblast markers (FSP-1, α-SMA, collagen I, Snail) and decreased levels of the FGFR1, glucocorticoid receptor (GR) and endothelial marker (CD31) compared to wild-type mice. In vitro, the pharmacological activation of α7nAChR with PNU282987 significantly inhibited IL-1β-induced EndMT, as shown by a reduced transition to the fibroblast-like phenotype and the expression of fibrotic markers. Moreover, the IL-1β-mediated activation of NF-κB pathway was suppressed by PNU282987. This anti-EndMT effect of α7nAChR was associated with regulation of Snail. Furthermore, Western blot analysis further revealed that the GR antagonist RU38486 could partially counteract the effect of PNU282987 on NF-κB expression. In conclusion, our results show that α7nAChR is involved in cardiac fibrosis by inhibiting EndMT, providing a novel approach to the treatment of MI.Skeletal muscle development and regeneration is governed by the combined action of Myf5, MyoD, Mrf4 and MyoG, also known as the myogenic regulatory factors (MRFs). These transcription factors are expressed in a highly spatio-temporal restricted manner, ensuring the significant functional and metabolic diversity observed between the different muscle groups. In this review, we will discuss the multiple layers of regulation that contribute to the control of the exquisite expression patterns of the MRFs in particular, and of myogenic genes in general. We will highlight all major regulatory processes that play a role in myogenesis from those that modulate chromatin status and transcription competence, such as DNA methylation, histone modification, chromatin remodeling, or non-coding RNAs, to those that control transcript and protein processing and modification, such as alternative splicing, polyadenylation, other mRNA modifications, or post-translational protein modifications. All these processes are exquisitely and tightly coordinated to ensure the proper activation, maintenance and termination of the myogenic process.Among the hallmarks of cholangiocarcinoma (CCA) progression and unresponsiveness to therapy is impaired ubiquitin-dependent degradation of nuclear tumor suppressor protein. In the previous stage, our research group found that as a key tumor suppressor, nuclear dysfunction of p27kip1 is closely related to chemotherapy resistance of CCA, but the specific mechanism is unclear. It was recently shown that p27kip1-driven tumors were strongly dependent on the SUMO pathway. RNF4, as the SUMO-targeted ubiquitin ligase (STUbL), identifies SUMOylated proteins as a substrate through sumo-interacting motifs (SIM) and causes its degradation via the ubiquitin proteasome pathway. Here we described that the expression of RNF4 was upregulated in CCA tissues and related to malignant features. Silencing RNF4 arrested human CCA cells at the G1 phase, which was associated with the upregulation of p27kip1 and the downregulation of its downstream cycle-related proteins. Silencing RNF4 inhibited cell proliferation and migration, increased cell apoptosis, and sensitized CCA cells to treatment of chemotherapeutic drugs in vitro. Immunofluorescence showed that p27kip1 and RNF4 were mainly co-located in the nucleus. Immunoprecipitation and Western blot showed that p27kip1 was a target protein for SUMOylation and high expression of RNF4 decreased the levels of nuclear p27kip1, enhanced the levels of ubiquitinated and SUMOylated p27kip1, indicating that RNF4 could regulate cell cycle progression via recognizing SUMOylated p27kip1 and facilitating its ubiquitination degradation. KRAS G12C inhibitor 19 ic50 These data indicate that RNF4-mediated ubiquitination degradation of SUMOylated proteins is a novel regulatory mechanism of p27kip1 dysfunction and CCA tumorigenesis, which provides a potential option for therapeutic intervention of CCA.Subchronic and chronic reference values (RfVs) were derived for 1,3-butadiene (BD) based upon its ability to cause reproductive and developmental effects observed in laboratory mice and rats. Metabolism has been well-established as an important determinant of the toxicity of BD. A major challenge to human health risk assessment is presented by large quantitative species differences in the metabolism of BD, differences that should be accounted for when the rodent toxicity responses are extrapolated to humans. The methods of Fred et al. (2008)/Motwani and Törnqvist (2014) were extended and applied here to the noncancer risk assessment of using data-derived extrapolation factors to account for species differences in metabolism, as well as differences in cytotoxic potency of three BD metabolites. This approach made use of biomarker data (hemoglobin adducts) to quantify species differences in the internal doses of BD metabolites experienced in mice, rats and humans. Using these methods, the dose-response relationships in mice and rats exhibit improved concordance, and result in subchronic and chronic inhalation reference values of 29 and 10 ppm, respectively, for BD. Confidence in these reference values is considered high, based on high confidence in the key studies, medium-to-high confidence in the toxicity database, high confidence in the estimates of internal dose, and high confidence in the dose-response modeling.The anti-inflammatory and chemopreventive activities of aspirin (ASA) may be mediated through its cyclooxygenase inhibitor function. We have previously shown that ASA can protect against UVR-induced skin inflammation and DNA damage; however, the role of inflammation in UV-induced DNA damage and the mechanism underlying ASA protection are poorly characterized. Using immunodeficient NOD scid gamma mice and immunocompetent C57BL/6 mice treated with immune cell‒depleting antibodies, we found that inflammation was not required for UVB-induced 8-oxoguanine and cyclobutane pyrimidine dimers in vivo. Unlike ASA, neither its immediate metabolite salicylate nor the cyclooxygenase inhibitor indomethacin reduced UVB-induced 8-oxoguanine or cyclobutane pyrimidine dimers in melanocyte Melan-a or keratinocyte HaCat cells in vitro. Moreover, addition of prostaglandin E2 did not reverse the protective effect of ASA on UVB-treated cells. Phosphorylation of the 5' AMP protein kinase, observed in ASA-treated cells, could be blocked by the 5' AMP protein kinase inhibitor compound C. Compound C or 5' AMP protein kinase knockdown partially reduced ASA-mediated protection against UVB-induced DNA damage. Finally, injection of compound C partially reversed the protective effect of ASA on UVB-treated mouse skin in vivo. These studies suggest that ASA confers protection against UVB-induced DNA damage through the activation of 5' AMP protein kinase rather than through cyclooxygenase inhibition.To facilitate nationwide epidemiological research on advanced cutaneous squamous cell carcinoma (cSCC), that is, locally advanced, recurrent, or metastatic cSCC, we sought to develop and validate a rule-based algorithm that identifies advanced cSCC from pathology reports. The algorithm was based on both hierarchical histopathological codes and free text from pathology reports recorded in the National Pathology Registry. Medical files from the Erasmus Medical Center of 186 patients with stage III/IV/recurrent cSCC and 184 patients with stage I/II cSCC were selected and served as the gold standard to assess the performance of the algorithm. The rule-based algorithm showed a sensitivity of 91.9% (95% confidence interval = 88.0‒95.9), a specificity of 96.7% (95% confidence interval = 94‒2-99.3), and a positive predictive value of 78.5% (95% confidence interval = 74.2‒82.8) for all advanced cSCC combined. The sensitivity was lower per subgroup locally advanced (52.3‒86.2%), recurrent cSCC (23.3%), and metastatic cSCC (70.0%). The specificity per subgroup was above 97%, and the positive predictive value was above 78%, with the exception of metastatic cSCC, which had a positive predictive value of 62%. This algorithm can be used to identify advanced patients with cSCC from pathology reports and will facilitate large-scale epidemiological studies of advanced cSCC in the Netherlands and internationally after external validation.Arterial hypertension is a global public health concern. In the last few years, the interest in androgen deficiency has been growing, and the association between androgens and high blood pressure (BP) is still controversial. One purpose of this review was to summarize the available findings in order to clarify whether male sex steroid hormones have beneficial or harmful effect on BP. The second purpose was to enhance the recognition of the acute non-genomic sex-independent vasorelaxing effect of androgens. Remarkably, BP variation is expected to be a consequence of the androgen-induced vasorelaxation which reduces systemic BP; hence the in vivo vasodepressor, hypotensive, and antihypertensive responses of androgens were also analyzed. This article reviews the current understanding of the physiological regulation of vascular smooth muscle contractility by androgens. Additionally, it summarizes older and more recent data on androgens, and some of the possible underlying mechanisms of relaxation, structural-functional differences in the androgen molecules, and their designing ability to induce vasorelaxation.