Endocrine Disruption by Heavy Metals on Steroidogenesis in Model Systems

In this study human adrenocortical carcinoma cell line NCI-H295R was used as an in vitro biological model to study the effect of heavy metals on steroidogenesis. The cell cultures were exposed to different concentrations of cadmium (1.90; 3.90; 7.80; 15.60; 31.20; 62.50 μM of CdCl2), mercury (1.0; 5.0; 25; 50; 100 μM of HgCl2), nickel (3.90; 7.80; 15.60; 31.20; 62.50; 125; 250; 500 μM of NiCl2) and compared to control. Cell viability was measured by the metabolic activity (MTT) assay for estimation of mitochondria structural integrity. Quantification of sexual steroid production directly from aliquots of the medium was performed by enzyme linked immunosorbent assay (ELISA). Cadmium decreased the release of progesterone and testosterone already at a very low concentration (1.90 μM) of CdCl2, while the cell viability remained relatively high (> 75%) up to 7.80 μM of CdCl2 and significantly (P<0.01) decreased at 15.60 μM and higher concentrations of CdCl2. Concentration-dependent depression in testosterone production was detected particularly for higher concentration of HgCl2. Progesterone production was also decreased, but at the lower concentrations (1.0 and 5.0 μM) of HgCl2 this decline was lower compared to depression of testosterone. The cell viability significantly decreased at 25 μM and higher concentration of HgCl2. Results of the our study indicate dose dependent decreases in both sexual steroid hormones by NCI-H295R cell culture following a 48 h in vitro NiCl2 exposure. The lowest concentration of progesterone was significantly (P<0.01) detected in groups with the higher doses (≥ 500 μM) of NiCl2, which elicited significant cytotoxic effect. The testosterone production was decreased as well, but this decline was more pronounced compared to depression of progesterone. These results suggest that heavy metals have detrimental effects on steroid hormone synthesis even at very low concentrations and consecutively on reproductive physiology

A hybrid mass transport finite element method for Keller-Segel type systems

We propose a new splitting scheme for general reaction–taxis–diffusion systems in one spatial dimension capable to deal with simultaneous concentrated and diffusive regions as well as travelling waves and merging phenomena. The splitting scheme is based on a mass transport strategy for the cell density coupled with classical finite element approximations for the rest of the system. The built-in mass adaption of the scheme allows for an excellent performance even with respect to dedicated mesh-adapted AMR schemes in original variables

Transcriptome analysis reveals tumor microenvironment changes in glioblastoma

A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells.</p