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  • 1
    Online Resource
    Online Resource
    Identification of NHLRC1 as a Novel AKT Activator from a Lung Cancer Epigenome-Wide Association Study (EWAS)
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 18 ( 2022-09-14), p. 10699-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 18 ( 2022-09-14), p. 10699-
    Abstract: Changes in DNA methylation identified by epigenome-wide association studies (EWAS) have been recently linked to increased lung cancer risk. However, the cellular effects of these differentially methylated positions (DMPs) are often unclear. Therefore, we investigated top differentially methylated positions identified from an EWAS study. This included a putative regulatory region of NHLRC1. Hypomethylation of this gene was recently linked with decreased survival rates in lung cancer patients. HumanMethylation450 BeadChip array (450K) analysis was performed on 66 lung cancer case-control pairs from the European Prospective Investigation into Cancer and Nutrition Heidelberg lung cancer EWAS (EPIC HD) cohort. DMPs identified in these pre-diagnostic blood samples were then investigated for differential DNA methylation in lung tumor versus adjacent normal lung tissue from The Cancer Genome Atlas (TCGA) and replicated in two independent lung tumor versus adjacent normal tissue replication sets with MassARRAY. The EPIC HD top hypermethylated DMP cg06646708 was found to be a hypomethylated region in multiple data sets of lung tumor versus adjacent normal tissue. Hypomethylation within this region caused increased mRNA transcription of the closest gene NHLRC1 in lung tumors. In functional assays, we demonstrate attenuated proliferation, viability, migration, and invasion upon NHLRC1 knock-down in lung cancer cells. Furthermore, diminished AKT phosphorylation at serine 473 causing expression of pro-apoptotic AKT-repressed genes was detected in these knock-down experiments. In conclusion, this study demonstrates the powerful potential for discovery of novel functional mechanisms in oncogenesis based on EWAS DNA methylation data. NHLRC1 holds promise as a new prognostic biomarker for lung cancer survival and prognosis, as well as a target for novel treatment strategies in lung cancer patients.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231810699
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Post-Contrast Acute Kidney Injury after Acute Stroke—Insights from a German Tertiary Care Center
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 23 ( 2021-12-02), p. 5684-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 23 ( 2021-12-02), p. 5684-
    Abstract: Background: Our aim was to investigate the relationship between additional iodinated contrast medium (CM) application for acute stroke imaging and Post-Contrast Acute Kidney Injury (PC-AKI). Methods: We performed a retrospective analysis of consecutive patients with acute stroke who received a CT angiogram (CTA) with or without additional CT perfusion (CTP) at admission between 2017 and 2020. The primary endpoint was the incidence of PC-AKI. Potential causes of renal function impairment were recorded and logistic regression was performed to determine predictors of PC-AKI. Results: Of 3134 cases screened, n = 989 met the predefined inclusion criteria. PC-AKI occurred in 22 (5.4%) patients who received CTA only and 18 (3.1%) patients who received CTA and additional CTP (unadjusted OR, CI; 0.59, 0.29–1.05). In 31/40 (77.5%) patients who suffered PC-AKI, a non-CM-related cause of renal function impairment was identified. Stroke etiology (hemorrhagic vs. ischemic) and indicators of prior kidney disease were independent predictors of PC-AKI. Conclusions: Additional administration of CM for perfusion imaging in acute stroke did not show a relevant influence on the occurrence of PC-AKI. Patients with intracranial hemorrhage and/or prior kidney disease are at particular risk of developing AKI.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10235684
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 3
    Online Resource
    Online Resource
    Seasonality of Non-SARS, Non-MERS Coronaviruses and the Impact of Meteorological Factors
    MDPI AG ; 2021
    In:  Pathogens Vol. 10, No. 2 ( 2021-02-09), p. 187-
    Details
    In: Pathogens, MDPI AG, Vol. 10, No. 2 ( 2021-02-09), p. 187-
    Abstract: Background: Seasonality is a characteristic of some respiratory viruses. The aim of our study was to evaluate the seasonality and the potential effects of different meteorological factors on the detection rate of the non-SARS coronavirus detection by PCR. Methods: We performed a retrospective analysis of 12,763 respiratory tract sample results (288 positive and 12,475 negative) for non-SARS, non-MERS coronaviruses (NL63, 229E, OC43, HKU1). The effect of seven single weather factors on the coronavirus detection rate was fitted in a logistic regression model with and without adjusting for other weather factors. Results: Coronavirus infections followed a seasonal pattern peaking from December to March and plunged from July to September. The seasonal effect was less pronounced in immunosuppressed patients compared to immunocompetent patients. Different automatic variable selection processes agreed on selecting the predictors temperature, relative humidity, cloud cover and precipitation as remaining predictors in the multivariable logistic regression model, including all weather factors, with low ambient temperature, low relative humidity, high cloud cover and high precipitation being linked to increased coronavirus detection rates. Conclusions: Coronavirus infections followed a seasonal pattern, which was more pronounced in immunocompetent patients compared to immunosuppressed patients. Several meteorological factors were associated with the coronavirus detection rate. However, when mutually adjusting for all weather factors, only temperature, relative humidity, precipitation and cloud cover contributed independently to predicting the coronavirus detection rate.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    URL: Article
    DOI: 10.3390/pathogens10020187
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2695572-6
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  • 4
    Online Resource
    Online Resource
    Biomarkers of Vascular Injury and Type 2 Diabetes: A Prospective Study, Systematic Review and Meta-Analysis
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 8, No. 12 ( 2019-11-27), p. 2075-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 12 ( 2019-11-27), p. 2075-
    Abstract: Data on biomarkers of vascular injury and type 2 diabetes (T2D) risk from prospective studies are lacking. We evaluated seven biomarkers of vascular injury in relation to T2D. Additionally, a meta-analysis was performed. From the EPIC–Heidelberg cohort, 2224 participants were followed-up from baseline for 16 (median) years. E-Selectin, P-Selectin, intercellular adhesion molecule 3 (ICAM3), thrombomodulin, thrombopoietin, glycoprotein IIb/IIIa and fibrinogen levels were measured in baseline blood samples. The systematic review and meta-analysis included prospective studies identified through MEDLINE and Web of Science that investigated the association between mentioned biomarkers and T2D. The study population included 55% women, median age was 50 years, and 163 developed T2D. ICAM3 was associated with lower T2D risk (fully adjusted HRhighest vs. lowest tertile 0.62 (95% CI: 0.43, 0.91)), but no other studies on ICAM3 were identified. Overall, fifteen studies were included in the systematic review and meta-analysis (6,171 cases). E-Selectin was associated with higher T2D risk HRper SD: 1.34 (95% CI: 1.16, 1.54; I2 = 63%, n = 9 studies), while thrombomodulin was associated with lower risk HRper SD: 0.82 (95% CI: 0.71, 0.95; I2 = 0%, n = 2 studies). In the EPIC–Heidelberg, ICAM3 was associated with lower T2D risk. The meta-analysis showed a consistent positive association between E-Selectin and T2D. It was also suggestive of an inverse association between thrombomodulin and T2D, although further studies are needed to corroborate this finding.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm8122075
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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