Impact of ferroptosis on preeclampsia: A review Shan, Yuping; Guan, Chengcheng; Wang, Jingli ...
Biomedicine & pharmacotherapy,
November 2023, 2023-11-00, 20231101, 2023-11-01, Volume:
167
Journal Article
Peer reviewed
Open access
Preeclampsia (PE) is usually associated with the accumulation of reactive oxygen species (ROS) resulting from heightened oxidative stress (OS). Ferroptosis is a unique type of lipid ...peroxidation-induced iron-dependent cell death distinct from traditional apoptosis, necroptosis, and pyroptosis and most likely contributes considerable to PE pathogenesis. At approximately 10–12 weeks of gestation, trophoblasts create an environment rich in oxygen and iron. In patients with PE, ferroptosis-related genes such as HIF1 and MAPK8 are downregulated, whereas PLIN2 is upregulated. Furthermore, miR-30b-5p overexpression inhibits solute carrier family 11 member 2, resulting in a decrease in glutathione levels and an increase in the labile iron pool. At the maternal-fetal interface, physiological hypoxia/reperfusion and excessive iron result in lipid peroxidation and ROS production. Owing to the high expression of Fpn and polyunsaturated fatty acid-containing phospholipid-related enzymes, including acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyl-transferase 3, and spermidine/spermine N1-acetyltransferase 1, trophoblasts become more susceptible to OS and ROS damage. In stage 1, the injured trophoblasts exhibit poor invasion and incomplete uterine spiral artery remodeling caused by ferroptosis, leading to placental ischemia and hypoxia. Subsequently, ferroptosis marked by OS occurs in stage 2, eventually causing PE. We aimed to explore the new therapeutic target of PE through OS in ferroptosis.
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•Trophoblasts are more vulnerable to ferroptosis.•Ferroptosis may participate in two stages of preeclampsia.•The key pathways of ferroptosis may be useful in PE prevention and treatment.
Base editors are RNA-programmable deaminases that enable precise single-base conversions in genomic DNA. However, off-target activity is a concern in the potential use of base editors to treat ...genetic diseases. Here, we report unbiased analyses of transcriptome-wide and genome-wide off-target modifications effected by cytidine base editors in the liver of mice with phenylketonuria. The intravenous delivery of intein-split cytidine base editors by dual adeno-associated viruses led to the repair of the disease-causing mutation without generating off-target mutations in the RNA and DNA of the hepatocytes. Moreover, the transient expression of a cytidine base editor mRNA and a relevant single-guide RNA intravenously delivered by lipid nanoparticles led to ~21% on-target editing and to the reversal of the disease phenotype; there were also no detectable transcriptome-wide and genome-wide off-target edits. Our findings support the feasibility of therapeutic cytidine base editing to treat genetic liver diseases.
A metagenomic study was performed on 498 female and 40 male
mosquitos collected in August and September 2019 in Ticino, a region in southern Switzerland, to address the question regarding the risk of ...the local transmission of zoonotic viruses. A total of 13 viruses from seven different virus families and several unclassified viral taxa were identified. Reads of insect-specific flaviviruses were present in all pools, and a complete genome of aedes flavivirus was assembled and phylogenetically analysed. The most abundant virus was Wenzhou sobemo-like virus, assembled from 1.3 × 10
to 3.6 × 10
reads in each pool. In a pool of male mosquitos, a complete genome of aedes Iflavi-like virus was detected and phylogenetically analysed. Most importantly, genomes of human pathogenic viruses were not found. This is the first study to determine the virome of
from Switzerland and forms a baseline for future longitudinal investigations concerning the potential role of
as a vector of clinically relevant viruses.
Pleural mesothelioma (PM) is a cancer where epithelioid, biphasic and sarcomatoid histotypes are observed. Sarcomatoid PM is characterized by mesenchymal features. Multi-omics have been used to ...characterize the epithelial-to-mesenchymal (EMT) phenotype at the molecular level. We contribute to this effort by including the analysis of RNA editing. We extracted samples with the highest vs. lowest Epithelial score from two PM cohorts and observed increased RNA editing in introns and decreased RNA editing in 3'UTR upon EMT. The same was observed in primary PM primary cultures stratified by transcriptomics analysis into two groups, one of them enriched with mesenchymal features. Our data demonstrate that, as has been observed in other cancer types, RNA editing associates to EMT phenotype in PM.
Background Understanding the composition and dynamics of the upper respiratory tract microbiota in healthy infants is a prerequisite to investigate the role of the microbiota in patients with ...respiratory diseases. This is especially true in early life, when the immune system is in development. Objective We sought to describe the dynamics of the upper respiratory tract microbiota in healthy infants within the first year of life. Methods After exclusion of low-quality samples, microbiota characterization was performed by using 16S rDNA pyrosequencing of 872 nasal swabs collected biweekly from 47 unselected infants. Results Bacterial density increased and diversity decreased within the first year of life ( R 2 = 0.95 and 0.73, respectively). A distinct profile for the first 3 months of life was found with increased relative abundances of Staphlyococcaceae and Corynebacteriaceae (exponential decay: R 2 = 0.94 and 0.96, respectively). In addition, relative bacterial abundance and composition differed significantly from summer to winter months. The individual composition of the microbiota changed with increasing time intervals between samples and was best modeled by an exponential function ( R 2 = 0.97). Within-subject dissimilarity in a 2-week time interval was consistently lower than that between subjects, indicating a personalized microbiota. Conclusion This study reveals age and seasonality as major factors driving the composition of the nasal microbiota within the first year of life. A subject's microbiota is personalized but dynamic throughout the first year. These data are indispensable to interpretation of cross-sectional studies and investigation of the role of the microbiota in both healthy subjects and patients with respiratory diseases. They might also serve as a baseline for future intervention studies.
Soil microorganisms are key transformers of mercury (Hg), a toxic and widespread pollutant. It remains uncertain, however, how long-term exposure to Hg affects crucial microbial functions, such as ...litter decomposition and nitrogen cycling. Here, we used a metagenomic approach to investigate the state of soil functions in an agricultural floodplain contaminated with Hg for more than 80 years. We sampled soils along a gradient of Hg contamination (high, moderate, low). Hg concentrations at the highly contaminated site (36 mg kg
–1
dry soil on average) were approximately 10 times higher than at the moderately contaminated site (3 mg kg
–1
dry soil) and more than 100 times higher than at the site with low contamination (0.25 mg kg
–1
dry soil; corresponding to the natural background concentration in Switzerland). The analysis of the CAZy and NCyc databases showed that carbon and nitrogen cycling was not strongly affected with high Hg concentrations, although a significant change in the beta-diversity of the predicted genes was observed. The only functional classes from the CAZy database that were significantly positively overrepresented under higher Hg concentrations were genes involved in pectin degradation, and from the NCyc database dissimilatory nitrate reduction and N-fixation. When comparing between low and high Hg concentrations the genes of the EggNOG functional category of inorganic ion transport and metabolism, two genes encoding Hg transport proteins and one gene involved in heavy metal transport detoxification were among those that were highly significantly overrepresented. A look at genes specifically involved in detoxification of Hg species, such as the
mer
and
hgc
genes, showed a significant overrepresentation when Hg contamination was increased. Normalized counts of these genes revealed a dominant role for the phylum
Proteobacteria
. In particular, most counts for almost all
mer
genes were found in
Betaproteobacteria
. In contrast,
hgc
genes were most abundant in
Desulfuromonadales
. Overall, we conclude from this metagenomic analysis that long-term exposure to high Hg triggers shifts in the functional beta-diversity of the predicted microbial genes, but we do not see a dramatic change or breakdown in functional capabilities, but rather functional redundancy.
Soil microorganisms such as Bacteria and Archaea play important roles in the biogeochemical cycling of soil nutrients, because they act as decomposers or are mutualistic or antagonistic symbionts, ...thereby influencing plant growth and health. In the present study, we investigated the vertical distribution of soil metagenomes to a depth of 1.5 m in Swiss forests of European beech and oak species on calcareous bedrock. We explored the functional genetic potential of soil microorganisms with the aim to disentangle the effects of tree genus and soil depth on the genetic repertoire, and to gain insight into the microbial C and N cycling. The relative abundance of reads assigned to taxa at the domain level indicated a 5-10 times greater abundance of Archaea in the deep soil, while Bacteria showed no change with soil depth. In the deep soil there was an overrepresentation of genes for carbohydrate-active enzymes, which are involved in the catalyzation of the transfer of oligosaccharides, as well as in the binding of carbohydrates such as chitin or cellulose. In addition, N-cycling genes (NCyc) involved in the degradation and synthesis of N compounds, in nitrification and denitrification, and in nitrate reduction were overrepresented in the deep soil. Consequently, our results indicate that N-transformation in the deep soil is affected by soil depth and that N is used not only for assimilation but also for energy conservation, thus indicating conditions of low oxygen in the deep soil. Using shotgun metagenomics, our study provides initial findings on soil microorganisms and their functional genetic potential, and how this may change depending on soil properties, which shift with increasing soil depth. Thus, our data provide novel, deeper insight into the "dark matter" of the soil.
Melting process of core–shell nanoparticles is different from Janus nanoparticles. Display omitted
•During the melting process of Ag–Cu Janus nanoparticles, the melted Ag atoms flow around Cu atoms, ...promoting the melting of Cu.•The melting of core–shell Ag–Cu nanoparticles depends on the ratio between particle size and shell thickness.•The size dependent melting temperature of nanoparticles can be explained by Bond-Energy model.
Molecular dynamics simulations have been used to explore the melting process of Ag–Cu nanoparticles (NPs) with core–shell and Janus structures. The melting temperature of Cu/Ag core/shell NPs will be lower than that of pure Cu NPs of same size due to the before melted Ag atoms. However, the Ag/Cu core/shell NPs have higher thermal stability than pure Ag NPs of same sizes. The melting of core–shell NPs depends on the ratio between particle size and shell thickness. The melting of Janus NPs starts from the Ag atoms, independent of the composition of Ag. During the melting process of Janus Ag–Cu NPs, the melted Ag atoms will flow around Cu atoms, promoting the melting of Cu. The melting temperature of Janus NPs depends on the Ag–Cu ratio.
Bats are increasingly recognized as reservoirs for many different viruses that threaten public health, such as Hendravirus, Ebolavirus, Nipahvirus, and SARS- and MERS-coronavirus. To assess spillover ...risk, viromes of bats from different parts of the world have been investigated in the past. As opposed to most of these prior studies, which determined the bat virome at a single time point, the current work was performed to monitor changes over time. Specifically, fecal samples of three endemic Swiss bat colonies consisting of three different bat species were collected over three years and analyzed using next-generation sequencing. Furthermore, single nucleotide variants of selected DNA and RNA viruses were analyzed to investigate virus genome evolution. In total, sequences of 22 different virus families were found, of which 13 are known to infect vertebrates. Most interestingly, in a Vespertilio murinus colony, sequences from a MERS-related beta-coronavirus were consistently detected over three consecutive years, which allowed us to investigate viral genome evolution in a natural reservoir host.
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