Pregnancy exposure to phenols and anthropometric measures in gestation and at birth

alexandrossfakianakis shared this article with you from Inoreader Pregnancy exposure to phenols and anthropometric measures in gestation and at birth via Epidemiology - Published Ahead-of-Print Background: Some synthetic phenols alter pathways involved in fetal development. Despite their high within-subject temporal variability, earlier studies relied on spot urine samples to assess pregnancy exposure. In this study, we examined associations between prenatal phenol exposure and fetal growth. Methods: We measured concentrations of two bisphenols, four parabens, benzophenone-3, and triclosan in 478 pregnant women in two weekly pools of 21 samples each, collected at 18 and 34 gestational weeks. We used adjusted linear regressions to study associations between phenol concentrations and growth outcomes assessed twice during pregnancy and at birth. Results: Benzophenone-3 was positively associated with all ultrasound growth parameters in at least one time point, in males but not females. In females, butylparaben was negatively associated with third trimester abdominal circumference and weight at birth. We observed isolated associations for triclosan (negative) and for methylparaben and bisphenol S (positive) and late pregnancy fetal growth. Conclusions: Our results suggest associations between prenatal exposure to phenols and fetal growth. Benzophenone-3 was the exposure most consistently (positively) associated across all growth parameters. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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Prognostic Nutrıtıonal Index: Is It Assocıated wıth The Prognosıs of Crımean Congo Hemorrhagıc Fever?

alexandrossfakianakis shared this article with you from Inoreader Prognostic Nutrıtıonal Index: Is It Assocıated wıth The Prognosıs of Crımean Congo Hemorrhagıc Fever? via Journal of Medical Virology Abstract Introduction The prognostic nutritional index (PNI) is calculated using total serum lymphocyte counts and albumin levels. We aimed to analyze the role of PNI in predicting intensive care unit (ICU) referral and mortality in patients with Crimean Congo Hemorrhagic Fever (CCHF). Materials and Methods Our target population was adult (age>18) patients who presented between March 2015 and October 2021 within five days of symptom emergence and were diagnosed with CCHF. The predictive value of PNI was analyzed by the ROC analysis. The patients were categorized based on the severity grading scores (SGS) as mild, moderate, and severe. The relationship between PNI and ICU referral and mortality was analyzed by logistic regression analysis. Results Overall, 115 patients with the diagnosis of CCHF were included. 13,9% (n=16) of the patients were referred to ICU while 11,3% (n=13) died. A comparison of the patients with different SGS grades revealed that they were significantly different regarding PNI (p<0,001). There was a significant negative correlation between PNI and SGS (r=-0,662; p<0,001). PNI had a PV regarding ICU referral and mortality ((AUC=0,723 95% CI: 0,609-0,836, p=0,004, (AUC=0,738 95% CI: 0,613-0,863, p=0,005)). The PNI threshold was 36,1 for ICU referral and mortality. The rates of female patients, hospitalization periods longer than one week, platelet apheresis replacement, diabetes mellitus, bleeding history, ICU admission, and mortality were significantly higher in patients with a PNI of lower than 36,1 (p<0,05). Conclusion PNI can predict ICU referral and mortality in patients admitted due to CCHF. This article is protected by copyright. All rights reserved. View on Web

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A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome

alexandrossfakianakis shared this article with you from Inoreader A novel homozygous missense mutation in the <i>FASTKD2</i> gene leads to Lennox-Gastaut syndrome via Journal of Human Genetics - Issue - nature.com science feeds Journal of Human Genetics, Published online: 21 June 2022; doi:10.1038/s10038-022-01056-7 A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome View on Web

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FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1

alexandrossfakianakis shared this article with you from Inoreader FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1 via Neuro-Oncology Advance Access Abstract Background We previously report that yes-associated protein (YAP), the core downstream effector of Hippo pathway, promotes the malignant progression of glioblastoma (GBM). However, although classical regulatory mechanisms of YAP are well explored, how YAP is modulated by the Hippo-independent manner remains poorly understood. Meanwhile, the non-receptor tyrosine kinase Fyn-related kinase (FRK), which exhibits low expression and possesses tumor suppressor effects in GBM, is reported to be involved in regulation of protein phosphorylation. Here, we examined whether FRK could impede tumor progression by modulating YAP activities. Methods Human GBM cells and intracranial GBM model were used to assess the effects of FRK and YAP on the malignant biological behaviors of GBM. Immunoblotting and immunohistochemistry were used to detect the expression of core proteins in GBM tissues. Co-immunoprecipitation, proximity ligation assay, luci ferase assay and ubiquitination assay were utilized to determine the protein-protein interactions and related molecular mechanisms. Results The expression levels of FRK and YAP were inversely correlated with each other in glioma tissues. In addition, FRK promoted the ubiquitination and degradation of YAP, leading to tumor suppression in vitro and in vivo. Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP. Siah1 is required for YAP destabilization initiated by FRK. Conclusions We identify a novel mechanism by which FRK orchestrates tumor-suppression effect through phosphorylating YAP and inducing its ubiquitination by Siah1. FRK-Siah1-YAP signaling axis may serve as a potential therapeutic target for GBM treatment. View on Web

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Oct4A palmitoylation modulates tumorigenicity and stemness in human glioblastoma cells

alexandrossfakianakis shared this article with you from Inoreader Oct4A palmitoylation modulates tumorigenicity and stemness in human glioblastoma cells via Neuro-Oncology Advance Access Abstract Background Glioblastoma multiforme and other solid malignancies are heterogeneous, containing subpopulations of tumor cells that exhibit stem characteristics. Oct4, also known as POU5F1, is a key transcription factor in the self-renewal, proliferation, and differentiation of stem cells. Although it has been detected in advanced gliomas, the biological function of Oct4, and transcriptional machinery maintained by the stemness of Oct4 protein-mediated glioma stem cells (GSC), has not been fully determined. Methods The expression of Oct4 variants was evaluated in brain-cancer cell lines, and in brain-tumor tissues, by quantitative real-time PCR, western blotting, and immunohistochemical analysis. The palmitoylation level of Oct4A was determined by the acyl-biotin exchange method, and the effects of palmitoylation Oct4A on GSCs were investigated by a series of in vitro (neuro-sphere formation assay, double immunofluorescence, pharmacological treatment, luciferase assay, and coimmunoprecipitation) and in vivo (xenograft model) experiments. Results Here, we report that all three variants of Oct4 are expressed in different types of cerebral cancer, while Oct4A is important for maintaining tumorigenicity in GSCs. Palmitoylation mediated by ZDHHC17 was indispensable for preserving Oct4A from lysosome degradation to maintain its protein stability. Oct4A palmitoylation also helped to integrate Sox4 and Oct4A in the SOX2 enhancement subregion to maintain the stem performance of GSCs. We also designed Oct4A palmitoylation competitive inhibitors, inhibiting the self-renewal ability and tumorigenicity of GSCs. Conclusions These findings indicate that Oct4A acts on the tumorigenic activity of glioblastoma, and Oct4A palmitoylation is a candidate therapeutic target. View on Web

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circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

alexandrossfakianakis shared this article with you from Inoreader circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 21 June 2022; doi:10.1038/s41368-022-00184-2 circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis View on Web

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