scholarly journals The influence of metallic ions from CoCr28Mo6 on the osteogenic differentiation and cytokine release of human osteoblasts

2015 ◽  
Vol 1 (1) ◽  
pp. 498-502 ◽  
Author(s):  
A Jonitz-Heincke ◽  
M Schröder ◽  
D Hansmann ◽  
S. Utzschneider ◽  
J.P. Kretzer ◽  
...  

AbstractInflammatory reactions associated with osteolysis and implant loosening can be the result of generated CoCr particles and the simultaneous release of ions, which are the consequence of wear at the articulating surfaces of metallic implants. By now, there is little knowledge about the influence of CoCr ions on the viability of human osteoblasts (hOB).Therefore, metallic ions were generated from solid CoCr28Mo6 alloys using electric potentials against hydrogen bridge electrodes. For the cell experiments, hOBs (n ≥ 4) in the third passage were used. Cells were cultured for 24 h before incubated with the generated ion solution in two different concentrations (100 µg/l and 500 µg/l in DMEM with 10 % FCS). Cells incubated without ions served as controls. After 48 h and 96 h cell viability was determined (WST-1 assay, live-dead-stainings). Additionally, gene expression levels of osteogenic markers and cytokines were analysed.A significant increase of metabolic activity and vital cells could be shown for both ion concentrations. Gene expression of alkaline phosphatase and Col1 was highly induced after 96 h for 100 µg/l whereas Col1 protein was significantly reduced on both time points (48 h: p=0.008 (100 µg/l, 500 µg/l); 96 h: p=0,029 (500 µg/l)) compared to the control. Additionally, MMP1 expression was decreased after 48 h and 96 h. IL6 mRNA was concentration-dependent increased after 48 h whereas a significant decrease could be shown for the highest ion concentration (p=0.029). Compared to the lower ion concentration, IL8, MCP1 (p=0.029) and TNF mRNA were clearly reduced for the higher ion solution after 96 h. Our results suggest that ions from CoCr28Mo6 alloys have only marginal effects on osteoblast viability whereas Col1 expression is reduced and cytokine release is induced. In further studies, the effects of metallic ions and particles from CoCr28Mo6 on other cells will be examined.

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.


Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1874
Author(s):  
Alberto Elmi ◽  
Nadia Govoni ◽  
Augusta Zannoni ◽  
Martina Bertocchi ◽  
Chiara Bernardini ◽  
...  

Roe deer are seasonal breeders with a complete yearly testicular cycle. The peak in reproductive activity is recorded during summer, the rutting period, with the highest levels of androgens and testicular weight. Melatonin plays a pivotal role in seasonal breeders by stimulating the hypothalamus–pituitary–gonads axis and acting locally; in different species, its synthesis within testes has been reported. The aim of this study was to evaluate the physiological melatonin pattern within roe deer testes by comparing data obtained from animals sampled during pre- and post-rut periods. Melatonin was quantified in testicular parenchyma, along with the genetic expression of enzymes involved in its local synthesis (AANAT and ASMT) and function (UCP1). Melatonin receptors, MT1-2, were quantified both at protein and gene expression levels. Finally, to assess changes in reproductive hormonal profiles, testicular dehydroepiandrosterone (DHEA) was quantified and used for a correlation analysis. Melatonin and AANAT were detected in all samples, without significant differences between pre- and post-rut periods. Despite DHEA levels confirming testicular involution during the post-rut period, no correlations appeared between such involution and melatonin pathways. This study represents the first report regarding melatonin synthesis in roe deer testes, opening the way for future prospective studies in the physiology of this species.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 767-768
Author(s):  
Vijay Varma ◽  
Youjin Wang ◽  
Yang An ◽  
Sudhir Varma ◽  
Murat Bilgel ◽  
...  

Abstract While Alzheimer’s disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association is unclear. Using a novel, 3-step study design we examined the role of cholesterol catabolism in dementia by testing whether 1) the synthesis of the primary cholesterol breakdown products (bile acids (BA)) were associated with neuroimaging markers of dementia; 2) pharmacological modulation of BAs alters dementia risk; and 3) brain BA concentrations and gene expression were associated with AD. We found that higher serum concentrations of BAs are associated with lower brain amyloid deposition, slower WML accumulation, and slower brain atrophy in males. Opposite effects were observed in females. Modulation of BA levels alters risk of incident VaD in males. Altered brain BA signaling at the metabolite and gene expression levels occurs in AD. Dysregulation of peripheral cholesterol catabolism and BA synthesis may impact dementia pathogenesis through signaling pathways in the brain.


Agronomy ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 92
Author(s):  
Joon Seon Lee ◽  
Lexuan Gao ◽  
Laura Melissa Guzman ◽  
Loren H. Rieseberg

Approximately 10% of agricultural land is subject to periodic flooding, which reduces the growth, survivorship, and yield of most crops, reinforcing the need to understand and enhance flooding resistance in our crops. Here, we generated RNA-Seq data from leaf and root tissue of domesticated sunflower to explore differences in gene expression and alternative splicing (AS) between a resistant and susceptible cultivar under both flooding and control conditions and at three time points. Using a combination of mixed model and gene co-expression analyses, we were able to separate general responses of sunflower to flooding stress from those that contribute to the greater tolerance of the resistant line. Both cultivars responded to flooding stress by upregulating expression levels of known submergence responsive genes, such as alcohol dehydrogenases, and slowing metabolism-related activities. Differential AS reinforced expression differences, with reduced AS frequencies typically observed for genes with upregulated expression. Significant differences were found between the genotypes, including earlier and stronger upregulation of the alcohol fermentation pathway and a more rapid return to pre-flooding gene expression levels in the resistant genotype. Our results show how changes in the timing of gene expression following both the induction of flooding and release from flooding stress contribute to increased flooding tolerance.


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